rifampin and Staphylococcal-Infections

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death.. PubMed, Embase and Cochrane CENTRAL databases were searched from inception to 31 December 2022. Reference lists and PubMed citations of eligible studies were checked.. Two study authors independently identified randomized controlled trials (RCTs) involving adult participants with SAB, in which an intervention group received adjunctive rifampicin and the control group received usual care with or without a placebo. Dichotomous data (bacteriological and clinical failure and deaths) were analysed and pooled across studies using risk ratio (RR) with 95% confidence intervals (CI) using a Mantel-Haenszel random-effect model. The key variable of interest being whether rifampicin was used.. Six RCTs including 894 participants-of which 758 (85%) were from one trial-met the inclusion criteria. The addition of rifampicin to conventional treatment of SAB significantly reduced bacteriological failure by 59% (RR 0.41, 95% CI 0.21-0.81, I2 = 0%, number need to treat 27). However, it did not reduce clinical failure (RR 0.70, 95% CI 0.47-1.03, I2 = 0%) or deaths (RR 0.96, 95% CI 0.70-1.32, I2 = 0%). Further, it did not reduce the duration of bacteraemia, or the length of hospital stay. Adjunctive rifampicin reduced SAB recurrences (1% versus 4%, P = 0.01). Emergence of rifampicin resistance during treatment was uncommon (<1%).. Although adjunctive rifampicin reduced the risk of bacteriological failure and recurrences, we found no mortality benefit to support its use in SAB.

Topics: Adult; Bacteremia; Humans; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Vascular graft infection (VGI) remains an important complication with a high mortality and morbidity rate. Currently, studies focusing on the role of vascular graft coatings in the prevention of VGI are scarce. Therefore, the aims of this study were to survey and summarise key features of pre-clinical in vivo models that have been used to investigate coating strategies to prevent VGI and to set up an ideal model that can be used in future preclinical research.. A systematic review was conducted in accordance with the Preferred reporting items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in MEDLINE (PubMed), Embase, and Web of Science.. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). The type of animal model, graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated.. In total, 4 667 studies were identified, of which 94 papers focusing on in vivo testing were included. Staphylococcus aureus was the organism most used (n = 65; 67.7%). Most of the graft types were polyester grafts. Rifampicin was the most frequently used antibiotic coating (n = 43, 48.3%). In the outcome assessment, most studies mentioned colony forming unit count (n = 88; 91.7%) and clinical outcome (n = 72; 75%). According to the ToxRTool, 21 (22.3%, n = 21/94) studies were considered to be not reliable.. Currently published in vivo models are very miscellaneous. More attention should be paid to the methodology of these pre-clinical reports when transferring novel graft coatings into clinical practice. Variables used in pre-clinical reports (bacterial strain, duration of activity coating) do not correspond well to current clinical studies. Based on the results of this review, a proposal for a complete and comprehensive set up for pre-clinical invivo testing of anti-infectious properties of vascular graft coatings was defined.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Colony Count, Microbial; Disease Models, Animal; Feasibility Studies; Humans; Microbial Sensitivity Tests; Prosthesis-Related Infections; Reproducibility of Results; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity.. We performed this meta-analysis, aimed to explore the efficacy of adjunctive rifampin for the treatment of SAB.. Medical literatures were searched in the Pubmed, Medline, Embase and Cochrane databases up to October 2018. Patients with SAB received treatment with or without rifampin were included. The risk ratio (RR) and 95% confidence intervals (CI) of mortality, rate of bacteriological failure and relapse were estimated.. Seven articles (five randomized controlled trials and two retrospective cohort studies) enrolling 979 and 636 patients of SAB treated with and without rifampin, respectively, were included. There was no difference of mortality between the adjunctive rifampin therapy and standard therapy on SAB (RR: 0.771, 95% CI: 0.442 to 1.347, I2 = 70.4%). In the subgroup analyses, the decreased mortality was observed in the adjunctive rifampin treatment for patients without MRSA infection (RR: 0.509, 95% CI: 0.372 to 0.697, I2 = 8.8%). In addition, there was no difference of the rate of bacteriologic failure (RR: 0.602, 95% CI: 0.198 to 1.825, I2 = 0.0%) or relapse (RR: 0.574, 95% CI: 0.106 to 3.112, I2 = 77.9%) between the adjunctive rifampin therapy and standard therapy on SAB.. In general, insufficient evidence supported the efficacy of adjunctive use of rifampin for treatment of SAB, adding rifampin to standard therapy didn't decrease the incidence of death, rate of bacteriologic failure and relapse.

Topics: Bacteremia; Humans; Publication Bias; Randomized Controlled Trials as Topic; Rifampin; Risk; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer people with cystic fibrosis with a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.. To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including P aeruginosa) or increased adverse effects from drugs, or both.. Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE, clinical trial registries (Clinicaltrials.gov, WHO ICTRP, ISRCTN Registry), handsearching article reference lists and through contact with experts in the field.Date of the last search of the Group's Cystic Fibrosis Trials Register: 27 July 2017.Ongoing trials registries were last searched: 07 August 2017.. Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment.. The authors independently assessed all search results for eligibility. They used the GRADE methodology to assess the quality of the evidence.. The review includes two trials with a total of 106 participants with MRSA infection. In both trials the active treatment was oral trimethoprim and sulfamethoxazole combined with rifampicin; however, one trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. In both trials the control arm was observation only.Both trials reported successful eradication of MRSA in people with CF as an outcome; however, the definition used for MRSA eradication differed. The first trial (n = 45) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that, when compared to control, oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures, odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence); however, by day 168 of follow-up there was no difference in the proportion of participants who remained MRSA-negative in either treatment arm, OR 1.17 (95% CI 0.31 to 4.42) (low-quality evidence). In the second trial, successful eradication was defined as the absence of MRSA following treatment (oral co-trimoxazole and rifampicin with intranasal mupirocin or observation) in at least three cultures over a period of six months. At the time of reporting, 40 out of 61 participants had completed follow-up, but results showed no difference between groups. Eradication was achieved in 12 out 29 participants (41%) receiving active treatment, and in 9 out of 32 participants (28%) on the observation arm, OR 1.80 (95% CI 0.62 to 5.25) (very low-quality evidence).With regards to this review's secondary outcomes, these were reported in the first trial only. The trial reports that no differences were observed between the two arms in terms of pulmonary exacerbations (from screening to day 28), nasal colonisation, lung function, weight or participant-reported outcomes. While not a specific outcome of this review, investigators reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control, rate ratio 0.22 (95% CI 0.05 to 0.72) (P = 0.0102).. Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, by six months, the proportion of participants who remained MRSA-negative did not differ between treatment arms in either trial. Moreover, the longer-term clinical consequences in terms of lung function, mortality and cost of care, remain unclear.Using GRADE methodology, we judged the quality of the evidence provided by this review to be very low to low, due to potential biases from the open-label design and unclear detail reported in one trial. Based on the available evidence, it is the opinion of the authors that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.

Topics: Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint infections. It is a steroidal antibiotic and the only marketed member of the fusidane class. Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly. It has a novel structure and novel mode of action and, therefore, there is little cross-resistance with other known antibiotics. Many mutations can occur in the FusA gene that codes for EF-G, and some of these mutations can result in high-level resistance (minimum inhibitory concentration [MIC] > 64 mg/L), whereas others result in biologically unfit staphylococci that require compensatory mutations to survive. Low-level resistance (<8 mg/L) is more common and is mediated by fusB, fusC, and fusD genes that code for small proteins that protect EF-G-GDP from binding fusidic acid. The genes for these proteins are spread by plasmids and can be selected mostly by topical antibiotic use. Reports of resistance have led to combination use of fusidic acid with rifampin, which is superseded by the development of a new dosing regimen for fusidic acid that can be used in monotherapy. It consists of a front-loading dose to decrease the potential for resistance development followed by a maintenance dose. This dosing regimen is now being used in clinical trials in the United States for skin and refractory bone and joint infections.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Chronic Disease; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusidic Acid; Humans; Microbial Sensitivity Tests; Peptide Elongation Factor G; Protein Synthesis Inhibitors; Rifampin; Staphylococcal Infections

Coagulase-negative staphylococci (CoNS) are the leading cause of late-onset sepsis in neonatal intensive-care units (NICUs). Despite adequate therapeutic levels and in vivo susceptibility, vancomycin is not always adequate in clearing CoNS bacteremias and other theurapeutic regimens are warranted especially when dealing with persistent CoNS bacteremias.. Retrospective analysis of neonates with persistent CoNS bacteremias in a tertiary NICU in two study periods (January 2006 to December 2007 and January 2011 to December 2012). Demographics, clinical characteristics and antibiotics used were recorded. We also performed a literature review on the treatment options for persistent CoNS bacteremia.. Out of the 1485 admissions during the 4 years, 121 (8,1%) neonates developed CoNS bacteremia and 42 of them (34.7%) were persistent. The most common CoNS species was S.epidermidis (91%). Apart from the shorter mean duration of bacteremia (p = 0.003), during the second part of the study, no other differences were observed between the two study periods. Ten (23.8%) neonates were treated with vancomycin monotherapy. In 23 (54.7%) neonates, rifampicin was added to vancomycin. Linezolid was given to seven neonates (16.6%), whereas daptomycin was given to two neonates (4.7%). No differences were found when we compared the characteristics of neonates treated with different antibiotics. All neonates tolerated treatment well. Our literature review revealed 16 relevant studies, the majority of which are small case series.. The addition of rifampicin, linezolid and daptomycin in neonates with persistent CoNS bacteremia can provide useful therapeutic alternatives. Further studies are required to bring more insight into the field.

Topics: Anti-Infective Agents; Daptomycin; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Linezolid; Retrospective Studies; Rifampin; Sepsis; Staphylococcal Infections; Treatment Outcome; Vancomycin

BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Epidural Abscess; Humans; Laminectomy; Lumbar Vertebrae; Male; Middle Aged; Rifampin; Risk Factors; Schizophrenia; Spinal Stenosis; Staphylococcal Infections; Suction; Treatment Outcome; Vancomycin

The increasing number of prosthesis implantations and higher life expectancy lead to a growing number of periprosthetic infections (PPI). Optimal therapy necessitates interdisciplinary coordination of surgical and antimicrobial treatment. Challenges in the treatment are the increased occurrence of resistant pathogens, selection of adequate antimicrobial and surgical treatment strategies, inappropriate pretreatment and comorbidities of patients. Current treatment concepts lead to a high success rate in terms of infection eradication, when correctly applied. The individual expectations and underlying conditions of each patient must be considered when determining the therapy concept. The first step is to distinguish between acute and chronic infections. In acute infections the prosthesis can be retained but chronic infections necessitate a complete exchange of the prosthesis. Complicating factors, such as compromising soft tissue and bone conditions, osteomyelitis and infections caused by difficult-to-treat bacteria should, however, always be treated by a complete exchange of the prosthesis, even for acute infections. The antimicrobial treatment must be tailored to the causative agent, the surgical strategy as well as comorbidities and drug intolerances of the patient. It is important to distinguish between biofilm-active eradication therapy with rifampicin for gram-positive pathogens and quinolones for gram-negative organisms and suppression therapy. This article gives a structured presentation of the therapy algorithm.

Topics: Algorithms; Biofilms; Chronic Disease; Combined Modality Therapy; Debridement; Gentamicins; Humans; Joint Prosthesis; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Surgical Wound Infection

Combinations of rifampin and clindamycin or rifampin, metronidazole, and moxifloxcin have been reported as effective treatments for hidradenitis suppurativa (HS) Hurley Stage 1 and Hurley Stage 2.  Clinical trials suggest that for stage 1 and mild stage 2 HS, clindamycin 300 mg twice daily and rifampin 300 mg twice daily for 10 weeks can substantially abate HS in ~80% of cases and remit HS in ~50% of cases.  Another study notes use of rifampin-moxifloxacin-metronidazole given for 6 weeks, dosed as rifampin (10 mg/kg once daily), moxifloxacin (400 mg daily), and metronidazole (500 mg thrice daily) with the metronidazole stopped at week 6.   Rifampin and moxifloxacin were continued if the HS improved and side effects did not occur.  Using this triple antibiotic regimen remission occurred in 100% Hurley Stage 1, 80% Hurly Stage 2, and 16.7 % of Hurley Stage 3 HS.   The author typically gives HS clindamycin 300 mg and rifampin 300 mg, each twice daily, for 10 weeks and assesses if remission has occurred.  If the patient has not achieved remission the author continues the regimen as long as the patient's clinical status continues to improve without side effects.  The reasons why rifampin is so effective against HS have not been fully defined and might involve rifampin's (1) antibacterial effects (2) effects on bacterial biofilms (3) anti-inflammatory effects (4) effects against granulomas (5) and immunomodulatory effects on neutrophils.  It is notable that rifampin, although not first line, is an effective treatment for Clostridium difficile, a pathogen that arises during treatment with clindamycin.  Thus, rifampin enhances safety when rifampin and clindamycin are combined for the treatment of HS.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Biofilms; Clindamycin; Corynebacterium Infections; Drug Therapy, Combination; Granuloma; Hidradenitis Suppurativa; Humans; Immunologic Factors; Neutrophils; Rifampin; Staphylococcal Infections; Streptococcal Infections

Staphylococcus aureus bacteraemia (SAB) is associated with substantial morbidity and mortality. By surviving within leukocytes, S. aureus can evade both immunological defences and antimicrobial drugs, thus facilitating haematogenous dissemination. We performed a systematic review to determine whether antimicrobials with intracellular activity improve outcomes in SAB when used as an adjunct to β-lactam or glycopeptide monotherapy. The Pubmed/MEDLINE, Embase and Cochrane databases were systematically searched for eligible studies that reported on the use of first-line antimicrobials plus a single additional antimicrobial of interest in patients with SAB (any cause). Six relevant studies were identified, all reporting on rifampicin use. Four studies (three randomized controlled trials and one cohort) reported on adults with SAB, including 54 patients treated with adjunctive rifampicin and 44 standard-therapy controls. Estimated across all of these studies, adjunctive rifampicin was associated with trends towards reduced all-cause mortality and reduced clinical or bacteriological failure. The fifth study indicated that adjunctive rifampicin accelerates the resolution of persistent SAB in neonates. Data from the sixth study were considered flawed owing to differences in co-morbidities between groups. Limited data suggest that rifampicin-induced hepatitis is not clinically significant but that drug interactions are. In conclusion, adjunctive rifampicin may improve outcomes in SAB when used as an adjunct to β-lactam or glycopeptide monotherapy.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Humans; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Prosthetic joint infection (PJI) is a serious complication of arthroplasty that is associated with significant mortality, morbidity and costs. PJI is difficult to cure because causative bacteria form and persist in biofilm adherent to the prosthesis surface. PJI can be classified into early, delayed or late according to the time of onset after insertion of the prosthesis, and this classification can help determine pathogenesis and appropriate management. Traditional treatment has been with prolonged intravenous antibiotics and prosthesis exchange, which has been successful in treating infection but is technically difficult and has high rates of associated morbidity. On the basis of in vitro and animal studies, interest has turned to the use of antimicrobials that are particularly active against biofilm-associated bacteria. Recent clinical evidence shows success in more than 77% of early PJI with surgical debridement, retention of prosthesis and the use of rifampicin-based combinations for staphylococcal PJI. Fluoroquinolones are preferred for Gram-negative PJI. Optimal antimicrobial treatment duration and the management of polymicrobial, enterococcal, fungal and culture-negative infections are still yet to be defined but will become more clear as the results of current research comes to hand.

Topics: Anti-Bacterial Agents; Arthroplasty; Australia; Biofilms; Debridement; Device Removal; Drug Administration Schedule; Drug Therapy, Combination; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections

Topics: Acetamides; Aminoglycosides; Animals; Anti-Bacterial Agents; beta-Lactams; Clindamycin; Daptomycin; Disease Models, Animal; Fluoroquinolones; Fosfomycin; Guidelines as Topic; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Tetracyclines; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Adult; Bacteremia; Drug Therapy, Combination; Emergencies; Female; Humans; Levofloxacin; Magnetic Resonance Imaging; Pregnancy; Psoas Abscess; Puerperal Disorders; Rifampin; Sacroiliitis; Staphylococcal Infections

One of the most dreaded complications after cochlear implantation is infection. These infections are a challenge due to lack of any data regarding optimal methods of investigation and management. More often than not, these patients have to undergo explantation and revision surgery. This paper presents a case report and literature review which focuses on the role of antibiotics and the need for early explantation in most biofilm-related infections of cochlear implants.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Biofilms; Child, Preschool; Cochlear Implants; Device Removal; Humans; Infusions, Intravenous; Male; Prosthesis-Related Infections; Recurrence; Reoperation; Rifampin; Rupture, Spontaneous; Staphylococcal Infections; Surgical Flaps; Tomography, X-Ray Computed

Staphylococcus spp. causes more than half of all osteoarticular infections of native structures or implanted material. The ability of Staphylococcus spp. to persist within infected bone tissue and to produce a bacterial biofilm, most notably in infections of implanted material, can lead to treatment failures and microbiological relapses. Rifampin is a cornerstone of the treatment of staphylococcal osteoarticular infections, particularly those of implanted material. Rifampin is a bactericidal antibiotic that diffuses very well within bone tissue and bacterial biofilms. The mechanism of action is inhibition of bacterial DNA transcription to mRNA independently from bacterial division, which results in activity against even dormant Staphylococcus spp. organisms. However, the high risk of emergence of rifampin-resistant mutants requires the concomitant administration of another antibiotic. Several antibiotics are recommended in the French guidelines issued by the French-Speaking Society for Infectious Diseases (Société de Pathologie Infectieuse de Langue Française [SPILF]). Here, we discuss the results from in vitro, animal, and clinical studies that explain the advantages and drawbacks of each antibiotic used with rifampin to treat osteoarticular infections due to Staphylococcus spp.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Biofilms; Drug Therapy, Combination; Humans; Infections; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus

The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Treatment Outcome

Methicillin resistant Staphylococcus aureus (MRSA) infection has classically been associated with institutional health care settings such as hospitals and nursing homes.. This article presents a case of community acquired MRSA infection resulting in severe osteomyelitis of the humerus, followed by a brief discussion and literature review.. Over the past few years, more community acquired cases of MRSA have occurred. Methicillin resistant S. aureus usually infects skin and soft tissue. Occasionally, a life threatening infection occurs involving the blood, lungs, heart and bone.

Topics: Adolescent; Anti-Bacterial Agents; Diagnosis, Differential; Fusidic Acid; Humans; Humerus; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rifampin; Shoulder Pain; Staphylococcal Infections; Tomography, X-Ray Computed

Vancomycin is often combined with a second antibiotic, most often rifampin or gentamicin, for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Published data from experiments evaluating these and other vancomycin-based combinations, both in vitro and in animal models of infection, often yield inconsistent results, however. More importantly, no data are available from randomized clinical trials to support their use, and some regimens are known to have potential toxicities. Clinicians should carefully reconsider the use of vancomycin-based combination therapies for the treatment of infection due to methicillin-resistant S. aureus.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Therapy, Combination; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Staphylococcus aureus causes severe life-threatening infections and has become increasingly common, particularly methicillin-resistant strains. Rifampin is often used as adjunctive therapy to treat S aureus infections, but there have been no systematic investigations examining the usefulness of such an approach.. A systematic review of the literature to identify in vitro, animal, and human investigations that compared single antibiotics alone and in combination with rifampin therapy against S aureus.. The methods of in vitro studies varied substantially among investigations. The effect of rifampin therapy was often inconsistent, it did not necessarily correlate with in vivo investigations, and findings seemed heavily dependent on the method used. In addition, the quality of data reporting in these investigations was often suboptimal. Animal studies tended to show a microbiologic benefit of adjunctive rifampin use, particularly in osteomyelitis and infected foreign body infection models; however, many studies failed to show a benefit of adjunctive therapy. Few human studies have addressed the role of adjunctive rifampin therapy. Adjunctive therapy seems most promising for the treatment of osteomyelitis and prosthetic device-related infections, although studies were typically underpowered and benefits were not always seen.. In vitro results of interactions between rifampin and other antibiotics are method dependent and often do not correlate with in vivo findings. Adjunctive rifampin use seems promising in the treatment of clinical hardware infections or osteomyelitis, but more definitive data are lacking. Given the increasing incidence of S aureus infections, further adequately powered investigations are needed.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Rifampin has been used for the eradication of Staphylococcus aureus (S. aureus) colonization in various populations of healthy and sick people.. We performed a systematic review of the evidence from randomized and nonrandomized controlled trials that compared the effectiveness and safety of a rifampin-based regimen with another regimen in eradicating S. aureus colonization from healthy and sick people.. Nine comparative trials (6 of which were randomized controlled trials) were included in our analysis. S. aureus was eradicated more commonly in patients receiving rifampin-containing regimens compared to monotherapy with other systemic agents (ciprofloxacin, cloxacillin, minocycline, or vancomycin), both during early and late (>1 month after therapy) post treatment evaluations (odds ratio [OR] 46.2, 95% confidence interval [CI] 14.4-148, and OR 8.8, 95% CI 3.4-22.5 respectively, 4 studies included). There was no statistically significant difference between rifampin monotherapy and combinations of rifampin with other topical (bacitracin) or systemic (cloxacillin and minocycline) antibiotics in eradicating S. aureus both in early and late evaluations (OR 1.5, 95% CI 0.5-4.4, and OR 1.6, 95% CI 0.7-3.7, respectively, 3 studies included). Eradication of methicillin-resistant S. aureus (MRSA) varied according to the type and duration of the rifampin-containing regimen. It ranged from 25% for the combination of rifampin with trimethoprim/sulfamethoxazole for 5 days to 100% for the combination of oral rifampin and minocycline for 14 days. Discontinuation of rifampin due to drug-related toxicity was necessary in 2% of 282 studied patients. Development of resistance of S. aureus to rifampin during and after treatment with a regimen containing rifampin ranged from 0% to 40% (7 studies) and overall 17% of the 236 patients for whom relevant data was reported.. The available evidence suggests that oral rifampin is an effective agent for the eradication of S. aureus carriage. However, development of antimicrobial resistance during and after treatment with rifampin occurs in a considerable proportion of patients; using rifampin in combination with another antimicrobial agent may decrease this resistance.

Topics: Administration, Oral; Anti-Bacterial Agents; Carrier State; Clinical Trials as Topic; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Male; Methicillin Resistance; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Rifampin has been studied as prophylaxis against Staphylococcus aureus-related infections in patients on dialysis.. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of oral rifampin with another regimen or no therapy in reducing S. aureus-related infections in dialysis patients.. Four RCTs evaluated oral rifampin (administered for 5 days every 3 months, or for 5 days once) as prophylaxis in dialysis patients. Oral rifampin with or without bacitracin was associated with less access-site infections with S. aureus compared with no treatment (odds ratio = 0.16, 95% confidence intervals: 0.06-0.44, 3 RCTs). There was no difference between prophylaxis with oral rifampin and topical mupirocin applied at the catheter site, for all studied outcomes, in the RCT comparing these regimens. Withdrawal from the study due to drug-related toxicity occurred in 7/107 (6.6%) of the studied patients with renal failure. Development of resistance of S. aureus to rifampin ranged from 0 to 18.2% (reported in three out of four included RCTs).. Prophylactic use of oral rifampin reduces access-site infections with S. aureus in patients with renal failure undergoing dialysis. However, development of toxicity and antimicrobial resistance during the treatment with rifampin occur in considerable proportions of patients, limiting its use and supporting the guidelines that recommend the use of local antibiotics at the exit site, such as mupirocin, for these indications. The available data are rather limited and more studies should be performed to examine this important clinical question.

Topics: Administration, Oral; Antibiotics, Antitubercular; Humans; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Community associated methicillin resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen typically associated with skin and soft tissue infection, with occasional reports of fatality in previously healthy children and young adults. We report a case of invasive CA-MRSA and highlight the potential impact of such infections on empirical treatment of staphylococcal infections.

Topics: Anti-Bacterial Agents; Child; Community-Acquired Infections; Drug Therapy, Combination; Genotype; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Soccer; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

A puzzling case report of a septicaemic post-surgical staphylococcal knee arthritis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin, despite apparently favourable in vitro susceptibility assays, but which rapidly resolved after i.v. followed by oral administration of linezolid is presented, and discussed in the context of the most recent literature evidence. The lack of response to a 14-d-long course of glycopeptides does not find explanation from the in vitro minimum inhibitory concentrations (MIC90) of involved organisms, which showed full susceptibility of Staphylococcus aureus to vancomycin and teicoplanin, and sensitivity of an accompanying Staphylococcus epidermidis isolated from blood cultures to vancomycin and rifampicin, with borderline 'intermediate' values found for teicoplanin. Since neither bone involvement nor abscess formation was of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been assured. From a clinical viewpoint, the introduction of a 2-week i.v. linezolid followed by 1 further week of oral linezolid led to complete clinical and microbiological cure, and an unexpected functional success.

Topics: Acetamides; Anti-Bacterial Agents; Arthritis, Infectious; Drug Therapy, Combination; HIV Infections; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Rifampin; Staphylococcal Infections; Teicoplanin; Vancomycin

To review the published clinical data assessing the role of adjunctive rifampin therapy for the treatment of staphylococcal central nervous system (CNS) infections.. A MEDLINE search (January 1966-March 2000) of English-language literature pertaining to CNS staphylococcal infections and rifampin was performed; tertiary sources were also used.. Human data and case reports were included, as no clinical trials have been published.. Retrospective reviews of rifampin used in combination with other antibiotics for serious bacterial infections show conflicting results. Few case reports have described clinical successes with adjunctive rifampin therapy for CNS infections.. The routine use of adjunctive rifampin for CNS infections cannot be justified.

Topics: Antibiotics, Antitubercular; Central Nervous System Diseases; Humans; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

One hundred and fifty-nine cases of clinical Staphylococcus aureus mastitis were analyzed to detect factors associated with bacteriological cure after therapy. On 100 Dutch dairy farms, data were collected from four clinical trials with five intramammary treatment regimes designed to treat beta-lactamase-positive pathogens. Infected quarters were treated three times, with a 12-h interval between treatments. Treatment was extended for 2 d if results of the trial treatment were, according to the owner, not satisfactory. The overall bacteriological cure rate was 52%. The bacteriological cure rate of clinical beta-lactamase-negative S. aureus mastitis was significantly higher than that of clinical beta-lactamase-positive S. aureus mastitis. Bacteriological cure was also significantly higher if somatic cell count of the cow was low at the milk recording prior to the onset of the clinical mastitis. The bacteriological cure rate of clinical beta-lactamase-negative S. aureus mastitis was also significantly higher after an extended treatment compared with no extended treatment. The seriousness of the various clinical symptoms and the bacteriological cure rate of clinical S. aureus mastitis were not associated.

Topics: Ampicillin; Animals; Antibiotics, Antitubercular; beta-Lactam Resistance; Cattle; Cefazolin; Cephalosporins; Cloxacillin; Colistin; Double-Blind Method; Female; Mastitis, Bovine; Milk; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim

Drug resistant tuberculosis has been recognized since chemotherapy first became available. However, drug resistance has increased in many countries, and recently strains resistant to both rifampicin and isoniazid (multidrug resistant tuberculosis) have emerged. This review discusses the epidemiology of multidrug resistant tuberculosis (MDRTB), and the control of MDRTB in healthcare facilities. Relevant papers for this review were identified by a systematic literature search on Medline. MDRTB is already established world-wide, and although the overall problem of resistance remains low in the UK, it is of significant clinical importance due to its high case-fatality, higher transmission risk, and complex treatment. The key elements of MDRTB control are prompt recognition, confirmation and treatment of cases, and the institution of strict infection control procedures to reduce the airborne spread of infection from infectious patients to others. This review emphasizes the importance of a multidisciplinary approach to management, with liaison between tuberculosis physicians, the microbiology department, infection control team, consultant in communicable disease, and occupational health.

Topics: Antibiotics, Antitubercular; Health Personnel; Humans; Isoniazid; Methicillin Resistance; Occupational Exposure; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis, Multidrug-Resistant

Coagulase negative staphylococci are the principal cause of prosthetic valve endocarditis but are a rare cause of native valve infections. However, the incidence of native valve endocarditis is increasing. Staphylococcus capitis is a coagulase negative staphylococcus with the capacity to cause endocarditis on native heart valves. Two cases of native valve endocarditis caused by S capitis are presented; both in patients with aortic valve disease. The patients were cured with prolonged intravenous vancomycin and rifampicin and did not need surgery during the acute phase of the illness. Five of the six previously described cases of endocarditis caused by this organism occurred on native valves and responded to medical treatment alone.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Aortic Valve; Endocarditis, Bacterial; Heart Valve Diseases; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Vancomycin

Numerous studies conducted in different countries and in different populations of patients on dialysis have consistently documented that a large proportion of such patients carry Staphylococcus aureus in their nares and that the risk of them becoming infected with their own strains is quite high. Furthermore, S. aureus infections can cause considerable morbidity and mortality in these patients. Thus, decolonization of the nares may prevent S. aureus infections and the attendant complications. The published data that support the use of rifampicin, intranasal mupirocin and povidone-iodine to prevent S. aureus infections in patients on dialysis are reviewed in detail.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Carrier State; Cost-Benefit Analysis; Humans; Mupirocin; Nose; Peritoneal Dialysis, Continuous Ambulatory; Povidone-Iodine; Renal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus

This case report demonstrates an unusual complication after anterior decompression and fusion of a lumbar burst fracture.. The treatment of this patient involved placement of a computed tomography-guided percutaneous drain and intravenous antibiotics to treat an infected retroperitoneal pseudomeningocele.. A case of an anterior retroperitoneal pseudomeningocele complicated by meningitis is presented. This pseudomeningocele occurred in a patient after an L3 burst fracture associated with a dural laceration.. The patient was admitted to the authors' trauma unit after a motor vehicle accident with an acute L3 fracture associated with incomplete paraplegia. He underwent an urgent anterior corpectomy, strut grafting, and instrumentation. At surgery, he was noted to have a large anterior dural laceration. After surgery, a large retroperitoneal pseudomeningocele developed that became infected with Staphylococcus epidermidis.. After placement of a computed tomography-guided percutaneous drain and intravenous antibiotics, the pseudomeningocele resolved. His anterior fusion healed uneventfully and his neurologic deficit improved dramatically.. A case of an anterior retroperitoneal pseudomeningocele complicated by meningitis is presented. This pseudomeningocele occurred in a patient after an L3 burst fracture associated with a dural laceration. The patient was treated successfully with computed tomography-guided percutaneous drain placement and intravenous antibiotics. He made an excellent functional recovery after a severe neurologic injury.

Topics: Adolescent; Drainage; Drug Therapy, Combination; Humans; Lumbar Vertebrae; Male; Meningitis; Meningocele; Retroperitoneal Space; Rifampin; Spinal Fractures; Staphylococcal Infections; Staphylococcus epidermidis; Tomography, X-Ray Computed; Vancomycin

A case of a 73-year-old woman with acute renal failure due to toxic shock syndrome (TSS) is reported. The patient was admitted to our hospital with the complaints of high fever, disturbance of consciousness and shock. Laboratory findings on admission were; CRP 25.11 mg/dl, WBC 35000/ microl, Plt 1.6 x 10(4)/ microl, GOT 155 U/l, GPT 65 U/l, CPK 4202 U/l (CPK-MM 96%), BUN 123 mg/dl and SCr 7.0 mg/dl. Because of anuria, hemodialysis was performed. This patient was treated with dopamine, methyl prednisolone (MP), frozen fresh plasma, AT III, antibiotics, and platelet transfusion. The bacterial cultures of blood and cerebrospinal fluid were negative, but MRSA was isolated subsequently from the pharynx and vagina. We investigated the production of toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins (SE). The isolated MRSA produced TSST-1, SEB and SEC. Accordingly, we made the diagnosis of TSS. After improvement of acute renal failure and the patient's general condition, MRSA persisted and TSST-1 was still found in the patient's blood. Finally we eradicated the MRSA and TSST-1 after administration of ciprofloxacin hydrochloride (CPFX) and Rifampicin (RFP).

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Toxins; Ciprofloxacin; Disseminated Intravascular Coagulation; Enterotoxins; Female; Humans; Methicillin Resistance; Rifampin; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Superantigens

Topics: Administration, Oral; Anti-Bacterial Agents; Anti-Infective Agents; Chronic Disease; Drug Therapy, Combination; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Osteomyelitis; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Female; Fusarium; Humans; Mycoses; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin; Skin; Spider Bites; Staphylococcal Infections

Methicillin-resistant staphylococci (MRS) have become major nosocomial pathogens during the last decade. The infections caused by these organisms occur predominantly in intensive care units, where extensive use of antibiotics takes place. Because of their multiresistant nature, these microorganisms frequently pose difficult therapeutic problems. Emergence of resistance during single-drug therapy further complicates the management of these infections. The use of combination therapy provides theoretically, at least, an answer to some of these difficulties; however, in-vitro and experimental studies need to be confirmed by adequately-controlled clinical trials. Aminoglycosides occasionally may play an important role as companion drugs for cephalosporins or vancomycin in the management of MRS infections. Other drugs such as rifampicin, teicoplanin, fluoroquinolones, and imipenem are to be more extensively investigated, as single-drug therapy or part of a combination regimen, for these difficult staphylococcal infections.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Drug Therapy, Combination; Glycopeptides; Imipenem; Methicillin; Norfloxacin; Oxacillin; Pefloxacin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Thienamycins; Vancomycin

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Cephalosporins; Clindamycin; Drug Combinations; Erythromycin; Humans; Methicillin; Metronidazole; Nalidixic Acid; Penicillin Resistance; Penicillins; Rifampin; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Anti-Bacterial Agents; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Humans; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Cerebrospinal Fluid Shunts; Drug Resistance, Microbial; Drug Therapy, Combination; Escherichia coli Infections; Gentamicins; Humans; Injections, Intravenous; Injections, Intraventricular; Klebsiella Infections; Leukocytes; Meningitis; Premedication; Pseudomonas Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tobramycin; Vancomycin

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Toxins; Blood; Carrier State; Drug Resistance, Microbial; Humans; Nose; Rifampin; Sepsis; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Stevens-Johnson Syndrome; Teichoic Acids

Topics: Abscess; Carrier State; Cloxacillin; Drug Interactions; Drug Therapy, Combination; Endocarditis, Bacterial; Furunculosis; Humans; Methicillin; Oxacillin; Penicillin Resistance; Phagocytes; Rifampin; Staphylococcal Infections

Vancomycin, introduced clinically about 30 years ago, has been used widely over the past decade because of the increasing incidence of methicillin-resistant staphylococci. Its bactericidal action, high and prolonged blood levels, the lack of development of resistant strains, and decreased adverse reactions with the more purified preparation now available, make it an excellent agent for staphylococcal infections due to strains resistant to the beta-lactam antibiotics. Recent articles reviewing the efficacy of vancomycin are summarized.

Topics: Aminoglycosides; Drug Synergism; Drug Therapy, Combination; Humans; Methicillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Vancomycin

There is controversy regarding methods employed for the detection of methicillin resistance in Staphylococcus aureus, and dispute whether infections caused by these organisms can be successfully treated with methicillin or similar antibiotic agents. Cell populations of methicillin-resistant Staph. aureus (MRSA) are heterogeneous with respect to the level of resistance expressed, but always contain a subpopulation of highly resistant cells which can neither be inhibited nor killed by beta-lactam antibiotic agents. Clinical experience confirms that in severe infections, particularly when host defences are imparied, the use of beta-lactam antibiotic agents to treat MRSA is associated with an unacceptably high failure rate. Current Victorian strains of MRSA are multiresistant. Thus vancomycin is the drug of choice for life-threatening infections, while the combination of fusidic acid either with flucloxacillin or with rifampicin is useful for infections of moderate severity.

Topics: Australia; beta-Lactamases; Cephalosporins; Drug Therapy, Combination; Floxacillin; Fusidic Acid; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Topics: Amphotericin B; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Gentamicins; Humans; Kanamycin; Lincomycin; Mycoses; Nalidixic Acid; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Sulfamethoxazole; Tetracyclines; Trimethoprim; Urinary Tract Infections; Vancomycin

A review of the literature suggests the following conclusions: 1) since its first practical use in 1965, namely over the past 10 years, there has been no drop in activity of Gentamicin on Staphylococcus aureus and on numerous other Staphylococcus and/or Micrococcus species. 2) In comparison with the other aminoglycosidic antibiotics employed up to the present, i.e. Streptomycin, Neomycin, Kanamycin, Amminosidine, and Framycetin, Gentamicin has demonstrated a much superior antistaphylococcic activity, and this has also been documented on numerous strains of staphylococci recalcitrant to Kanamycin, Streptomycin, Framycetin and Neomycin. This goes to prove the absence of any cross resistance between Kanamycin, Streptomycin, Framycetin and Neomycin on the one hand and Gentamycin on the other. 3) Along with Rifampicin, certain Cephalosporins (Cephalotine, Cephaloridine) and Pristinamycin-Virgimycin, Gentamicin must undoubtedly be considered a "greater" antibiotic as far as antistaphylococcic activity is concerned. It also has the advantage over other antistaphylococcic-acting antibiotics that only in exceptional cases does it give rise to resistant strains.

Topics: Cephalosporins; Cross Infection; Drug Resistance, Microbial; Framycetin; Gentamicins; Humans; Kanamycin; Microbial Sensitivity Tests; Neomycin; Paromomycin; Rifampin; Staphylococcal Infections; Staphylococcus; Streptomycin; Virginiamycin

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Carbenicillin; Cephalothin; Child; Child, Preschool; Cross Infection; Doxycycline; Drug Combinations; Gentamicins; Humans; Infant, Newborn; Infections; Lincomycin; Middle Aged; Nystatin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Tetracycline

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Chemical Phenomena; Chemistry; Dogs; Drug Resistance, Microbial; Female; Guinea Pigs; Humans; Male; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rabbits; Rats; Rifampin; Staphylococcal Infections; Tuberculosis

Topics: Anti-Bacterial Agents; Antitubercular Agents; Cephalosporins; Endocarditis, Bacterial; Enteritis; Gentamicins; Humans; Infections; Lincomycin; Meningitis; Penicillins; Rifampin; Sepsis; Staphylococcal Infections; Streptococcal Infections; Sulfonamides; Urinary Tract Infections; Vancomycin

To develop the 'Stronger Towns Index': a deprivation index that took into account characteristics of areas encompassing towns that may be eligible for redevelopment funding and explore how this index was associated with self-rated health and migration within England between 2001 and 2011.. There were areas in the lowest deciles of Town Strength who did not receive funding. After multiple adjustment, LS members living in areas with higher deciles were significantly more likely (7% to 38%) to report good health than those in the lowest decile in 2001. Remaining in the same decile between 2001 and 2011 was associated with 7% lower odds of good self-rated health in 2011.. It is important to consider health in towns when allocating funding. Areas in the Midlands may have missed out on funding which might help mitigate poor health.. Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.. This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.. Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.. Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant. In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO. Persistent gender and racial disparities in high-impact medical and critical care journals underscore the need to revise policies and strategies to encourage greater diversity in critical care research.. Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.. Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

Topics: Acetogenins; Acute Disease; Acute Kidney Injury; Administration, Intravenous; Aged; Albumins; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; alpha-Glucosidases; Anemia; Animals; Anthozoa; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Antigens, Bacterial; Antihypertensive Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascites; Asthma; Bacteria; beta-Lactamases; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding Sites; Biological Availability; Biomass; Borderline Personality Disorder; Brain; Brucella abortus; Brucella melitensis; Brucellosis; Calcium; Carbapenems; Case-Control Studies; Caseins; Cattle; CD8-Positive T-Lymphocytes; Ceftaroline; Cell Line; Cell Line, Tumor; Cell Physiological Phenomena; Cell Proliferation; Cephalosporins; Chemotherapy, Adjuvant; China; Chitin; Chlorella; Chlorophyll; Chlorophyll A; Chlorophyta; Cholangiocarcinoma; Cisplatin; Conotoxins; Contrast Media; Conus Snail; Cross-Sectional Studies; Cytokines; Decapodiformes; Deoxycytidine; Diagnostic and Statistical Manual of Mental Disorders; Dietary Fiber; Diterpenes; DNA Methylation; Dogs; Double-Blind Method; Drug Design; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Epidermis; Escherichia coli; Escherichia coli Infections; Extraintestinal Pathogenic Escherichia coli; Fatty Acids; Fatty Acids, Unsaturated; Fatty Acids, Volatile; Feasibility Studies; Feces; Female; Ferritins; Fluorodeoxyglucose F18; Gastrectomy; Gastrointestinal Microbiome; Gemcitabine; Glomerular Filtration Rate; Glucose; Glycerol; Granulocyte-Macrophage Colony-Stimulating Factor; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Immunoassay; Immunoglobulin G; India; Infant, Newborn; Infertility; Inflammation; Intensive Care Units; Iron; Iron Deficiencies; Kidney; Lacticaseibacillus rhamnosus; Laurencia; Leukocytes; Lipids; Liver Cirrhosis; Long Interspersed Nucleotide Elements; Longitudinal Studies; Male; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Mice; Microalgae; Microbial Sensitivity Tests; Microscopy; Middle Aged; Minerals; Molecular Conformation; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Myeloid Cells; Myeloid-Derived Suppressor Cells; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Nephropidae; Nicotinic Antagonists; Nitrogen; Obesity; Oxaliplatin; Paclitaxel; Panax; Pancreatic Neoplasms; Pancreatitis; Personality; Personality Disorders; Personality Inventory; Photobioreactors; Plant Extracts; Plasmalogens; Plasmids; Polymorphism, Genetic; Polynesia; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prebiotics; Predictive Value of Tests; Prognosis; Prolyl-Hydroxylase Inhibitors; Rabbits; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Nicotinic; Recombinant Proteins; Retrospective Studies; Rifampin; Risk Factors; RNA, Ribosomal, 16S; Salinity; Seaweed; Sensitivity and Specificity; Sepsis; Sesquiterpenes; Severity of Illness Index; Shock, Septic; Silicones; Single Photon Emission Computed Tomography Computed Tomography; Skin; Snails; Solubility; Solvents; Sputum; Staphylococcal Infections; Stomach Neoplasms; Stramenopiles; Structure-Activity Relationship; Technetium Tc 99m Exametazime; Technology; Terpenes; Tuberculosis; Tuberculosis, Multidrug-Resistant; Urinary Catheters; Urinary Tract Infections; Vascular Endothelial Growth Factor A; Virulence Factors; Water; Wound Healing

The evidence supporting rifampin combination therapy in prosthetic joint infections (PJI) is limited due to the lack of controlled studies. The aim of this study is to evaluate the effect of adding rifampin to conventional antimicrobial therapy in early staphylococcal PJIs treated with debridement and retention of the implant (DAIR).. In this multicenter randomized controlled trial, 99 patients with PJI after hip and knee arthroplasties were enrolled. They were randomly assigned to receive rifampin or not in addition to standard antimicrobial treatment with cloxacillin or vancomycin in case of methicillin resistance. The primary endpoint was no signs of infection after 2 years of follow-up.. Forty-eight patients were included in the final analyses. There were no differences in patient characteristics or comorbidities between the two groups. There was no significant difference in remission rate between the rifampin combination group (17 of 23 (74%)) and the monotherapy group (18 of 25 (72%), relative risk 1.03, 95% confidence interval 0.73 to 1.45, p = 0.88).. This trial has not proven a statistically significant advantage by adding rifampin to standard antibiotic treatment in acute staphylococcal PJIs.. The Regional Ethics Committee and the Norwegian Medicines Agency approved the study (EudraCT 2005-005494-29), and the study was registered at ClinicalTrials.gov at Jan 18, 2007 ( NCT00423982 ).

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cloxacillin; Debridement; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Time Factors; Treatment Outcome; Vancomycin

Few studies, based on a limited number of patients using non-uniform therapeutic protocols, have analyzed Methicillin-resistant Staphylococcus aureus (MRSA) eradication.. In a randomized multicenter trial conducted on patients with new-onset MRSA infection we evaluated the efficacy of an early eradication treatment (arm A) compared with an observational group (B). Arm A received oral rifampicin and trimethoprim/sulfamethoxazole (21 days). Patients' microbiological status, FEV1, BMI, pulmonary exacerbations and use of antibiotics were assessed.. Sixty-one patients were randomized. Twenty-nine (47.5%) patients were assigned to active arm A and 32 (52.5%) patients to observational arm B. Twenty-nine (47.5%) patients, 10 patients in arm A and 19 in arm B, dropped out of the study. At 6 months MRSA was eradicated in 12 (63.2%) out of 19 patients in arm A while spontaneous clearance was observed in 5 (38.5%) out of 13 patients in arm B. A per-protocol analysis showed a 24.7% difference in the proportion of MRSA clearance between the two groups (z = 1.37, P(Z>z) = 0.08). Twenty-seven patients, 15 (78.9%) out of 19 in arm A and 12 (92.3%) out of 13 in arm B, were able to perform spirometry. The mean (±SD) FEV1 change from baseline was 7.13% (±14.92) in arm A and -1.16% (±5.25) in arm B (p = 0.08). In the same period the BMI change (mean ±SD) from baseline was 0.54 (±1.33) kg/m2 in arm A and -0.38 (±1.56) kg/m2 in arm B (p = 0.08). At 6 months no statistically significant differences regarding the number of pulmonary exacerbations, days spent in hospital and use of antibiotics were observed between the two arms.. Although the statistical power of the study is limited, we found a 24.7% higher clearance of MRSA in the active arm than in the observational arm at 6 months. Patients in the active arm A also had favorable FEV1 and BMI tendencies.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Rifampin; Staphylococcal Infections; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach. Rifampin PK was best characterized by a one-compartment model; drug clearance increased with increasing size (body weight) and maturation (PNA). There were no adverse events related to rifampin. Simulated weight and PNA-based intravenous dosing regimens administered once daily (<14 days PNA, 8 mg/kg; ≥14 days PNA, 15 mg/kg) in infants resulted in comparable exposures to adults receiving therapeutic doses of rifampin against staphylococcal infections and TB. (This study has been registered at ClinicalTrials.gov under identifier NCT01728363.).

Topics: Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Prospective Studies; Rifampin; Staphylococcal Infections; Tuberculosis

Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.. In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.. Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).. Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.. UK National Institute for Health Research Health Technology Assessment.

Topics: Administration, Intravenous; Administration, Oral; Aged; Antibiotics, Antitubercular; Bacteremia; Community-Acquired Infections; Cross Infection; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Treatment Failure

Staphylococcal species account for more than 50% of periprosthetic joint infections (PJI) and antimicrobial therapy with rifampin-based combination regimens has been shown effective. The present study evaluates the safety and efficacy of clindamycin in combination with rifampin for the management of staphylococcal PJI.. In this retrospective cohort study, patients were included who received clindamycin-rifampin combination therapy to treat a periprosthetic hip or knee infection by Staphylococcus aureus or coagulase-negative staphylococci. Patients were treated according to a standardized treatment algorithm and followed for a median of 54 months. Of the 36 patients with periprosthetic staphylococcal infections, 31 had an infection of the hip, and five had an infection of the knee. Eighteen patients underwent debridement and retention of the implant (DAIR) for an early infection, the other 18 patients underwent revision of loose components in presumed aseptic loosening with unexpected positive cultures.. In this study, we report a success rate of 86%, with five recurrent/persistent PJI in 36 treated patients. Cure rate was 78% (14/18) in the DAIR patients and 94% (17/18) in the revision group. Five patients (14%) discontinued clindamycin-rifampin due to side effects. Of the 31 patients completing the clindamycin-rifampin regimen 29 patients (94%) were cured.. Combined therapy with clindamycin and rifampin is a safe, well tolerated and effective regimen for the treatment of staphylococcal periprosthetic infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Hip Prosthesis; Humans; Knee Prosthesis; Male; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Treatment Outcome

The evidence for using combination antimicrobial therapy (CoRx) in Staphylococcus aureus bacteraemia (SAB) is limited. We aimed to investigate whether CoRx is associated with higher survival or lower SAB-related late complications.. We performed a post hoc analysis of a prospective SAB cohort study. CoRx was defined as a cell wall-active antistaphylococcal agent plus either rifampicin, a fluoroquinolone, fosfomycin or an aminoglycoside. To adjust for survivor bias multivariable Cox models that included CoRx as a time-dependent covariable were calculated.. Of 964 evaluable patients, 512 (53%) received CoRx, most of them (301/512, 59%) rifampicin-containing CoRx. All-cause mortality after 30 and 90 days was similar for the two groups, although the patients in the CoRx group had more often endocarditis, deep-seated or disseminated infections and severe sepsis/septic shock. For the entire cohort, only age, comorbidity and severe sepsis/septic shock were associated with a higher mortality and infectious disease consultation, but not CoRx with a lower mortality. However, in the subgroup of patients with implanted foreign bodies or devices CoRx was independently associated with a lower mortality at 30 days (hazard ratio 0.6, 95% confidence interval 0.3-1.1) and at 90 days (hazard ratio 0.6, 95% confidence interval 0.4-0.9). SAB-related late complications in this subgroup occurred in 15 (10.6%) of 142 patients in the monotherapy group vs. nine (4.5%) of 202 patients in the CoRx group (p 0.03).. In a setting of optimized management of adult patients with SAB secured by infectious disease consultations, this observational study could not prove CoRx to be independently associated with improved survival or reduced late complications in the entire cohort. However, administration of CoRx may be associated with lower mortality and fewer SAB-related late complications in the subgroup of patients with implanted foreign bodies or devices. Prospective randomized trials should be performed to prove this benefit.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis; Treatment Outcome; Young Adult

The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection.. We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854).. Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group.. Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Rifampin; Staphylococcal Infections; Survival Analysis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pharmacokinetics of clindamycin in combination with rifampicin or levofloxacin were prospectively evaluated for the oral treatment of severe staphylococcal osteo articular infections.. Thirty-four patients (25 males, 9 females), with a mean age of 52.4 ± 17 years (range, 24-81 years), were randomly assigned either to the clindamycin-rifampicin or to the clindamycin-levofloxacin arm (control), following surgical debridement and intravenous adapted treatment. Trough and peak serum concentrations of clindamycin were measured at day-1 (D1), D15 and D30 of oral treatment. Cure was evaluated at a minimum of one year after the initiation of treatment.. The oral treatment was interrupted in 4 cases because of adverse events. Mean trough and peak serum concentrations of clindamycin in the clindamycin-rifampicin arm were lower than in the clindamycin-levofloxacin arm during the time of oral antibiotic regimen (0.79 ± 0.3 μg/ml vs 4.7 ± 1.2 μg/ml, p < 0.001, and 3.48 ± 1.1 μg/ml vs 10.2 ± 1.8 μg/ml, p < 0.001, respectively). A consistent decrease in clindamycin serum concentration was observed at each time-point of follow-up. At a mean of 23 ± 7.8 months (range, 12-47 months), 24 patients were available for clinical evaluation. No difference could be detected in the cure rates between the groups.. Our results indicate a significant influence of rifampicin on clindamycin pharmacokinetics using the oral route. Clindamycin serum concentrations (trough and peak) were systematically below the recommended therapeutic ranges when associated with rifampicin, as opposed to the control. Considering the potential risk of selection of mutant resistant to clindamycin, we do not recommend the clindamycin-rifampicin combination in the oral treatment of severe staphylococcal osteoarticular infection, unless clindamycin serum concentration is thoroughly controlled. The study has been registered on the clinicaltrials.gov website under the number NCT 01500837.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Rifampin; Serum; Staphylococcal Infections; Treatment Outcome; Young Adult

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) respiratory infection in cystic fibrosis (CF) has increased dramatically over the last decade, and is now affecting approximately 25% of patients. Epidemiologic evidence suggests that persistent infection with MRSA results in an increased rate of decline in FEV1 and shortened survival. Currently, there are no conclusive studies demonstrating an effective and safe treatment protocol for persistent MRSA respiratory infection in CF.. The primary objective of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation in combination with oral antibiotics in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. This is a two-center, randomized, double-blind, comparator-controlled, parallel-group study with 1:1 assignment to either vancomycin for inhalation (250 mg twice a day) or taste-matched placebo for 28 days in individuals with cystic fibrosis. In addition, both groups will receive oral rifampin, a second oral antibiotic - trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol determined - mupirocin intranasal cream, and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled: 20 will be randomized to vancomycin for inhalation and 20 to a taste-matched placebo. The primary outcome will be the presence of MRSA in sputum respiratory tract cultures 1 month after the conclusion of treatment. Secondary outcomes include the efficacy of the intervention on: FEV1% predicted, patient reported outcomes, pulmonary exacerbations, and MRSA colony-forming units found in respiratory tract sample culture.. Results of this study will provide guidance to clinicians regarding the safety and effectiveness of a targeted eradication strategy for persistent MRSA infection in CF.. This trial is registered at ClinicalTrials.gov (NCT01594827, received 05/07/2012) and is funded by the Cystic Fibrosis Foundation (Grants: PMEP10K1 and PMEP11K1).

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Child; Cystic Fibrosis; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Nebulizers and Vaporizers; Remission Induction; Research Design; Rifampin; Staphylococcal Infections; Vancomycin

Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation.. We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥ 18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤ 96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900 mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively.. This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.

Topics: Anti-Bacterial Agents; Bacteremia; Clinical Protocols; Humans; Rifampin; Sample Size; Staphylococcal Infections

Rifaximin is a poorly absorbed non-systemic antimicrobial agent used in various gastrointestinal disorders. Rifampin is pivotal for the treatment of staphylococcal foreign body infections and resistance develops rapidly during monotherapy. The close structural relation of rifaximin to rifampin may lead to cross-resistance. The aim of our study was to determine whether rifampin-resistance emerges in human skin staphylococci during or after oral intake of rifaximin.. Rifampin resistance of skin staphylococci in healthy volunteers during and after intake of rifaximin was determined by E-Test.. Seven out of eleven volunteers developed rifampin-resistant staphylococci after intake of rifaximin. A total of eleven rifampin-resistant and three rifampin-intermediate staphylococcal isolates were found. Before or during intake no resistant isolate was detected. Shortly after discontinuation the rifampin-resistant strains were primarily isolated from the perianal skin, a few weeks later they were found more frequently on the skin of the hands and lower arms.. Our data show that rifampin-resistant staphylococci emerge after intake of rifaximin. Since rifampin resistance is associated with treatment failure in staphylococcal foreign body infections, we conclude that rifaximin should be avoided in patients at risk for these infections.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Rifampin; Rifamycins; Rifaximin; Skin; Staphylococcal Infections; Staphylococcus

Oral therapies alternative to fluoroquinolones against staphylococcal chronic osteomyelitis have not been evaluated in comparative studies. Consecutive nonaxial Staphylococcus aureus chronic osteomyelitis cases were included in a comparative trial after debridement. Fifty patients were randomized: group A (n = 22) was treated with cloxacillin for 6 weeks intravenously plus 2 weeks orally (p.o.), and group B (n = 28) was treated with rifampin-cotrimoxazole for 8 weeks p.o. During follow-up (10 years), five relapses occurred: two (10%) in group A and three (11%) in group B. Foreign-body maintenance was associated with relapse (P = 0.016). Oral rifampin-cotrimoxazole treatment showed outcomes comparable to those for intravenous cloxacillin treatment.

Topics: Administration, Oral; Adult; Aged; Anti-Infective Agents; Cloxacillin; Drug Combinations; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Osteomyelitis; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage may reduce the risk of MRSA infection and prevent transmission of the organism to other patients.. To determine the efficacy of decolonization therapy, patients colonized with MRSA were randomized (3:1 allocation) to receive treatment (2% chlorhexidine gluconate washes and 2% mupirocin ointment intranasally, with oral rifampin and doxycycline for 7 days), or no treatment. Follow-up samples for MRSA culture were obtained from the nares, perineum, skin lesions, and catheter exit sites monthly for up to 8 months. The primary outcome measure was detection of MRSA at 3 months of follow-up. Univariate and multivariable analyses were performed to identify variables associated with treatment failure.. Of 146 patients enrolled in the study, 112 patients (87 treated; 25 not treated) were followed up for at least 3 months. At 3 months of follow-up, 64 (74%) of those treated had culture results negative for MRSA, compared with 8 (32%) of those not treated (P=.0001). This difference remained significant at 8 months of follow-up, at which time, 54% of those treated had culture results negative for MRSA (chi2=64.4; P<.0001, by log-rank test). The results of the multivariable analysis indicated that having a mupirocin-resistant isolate at baseline was associated with treatment failure (relative risk, 9.4; 95% confidence interval, 2.8-31.9; P=.0003), whereas decolonization therapy was protective (relative risk, 0.1; 95% confidence interval, 0.04-0.4; P=.0002). Mupirocin resistance emerged in only 5% of follow-up isolates.. Treatment with topical mupirocin, chlorhexidine gluconate washes, oral rifampin, and doxycycline for 7 days was safe and effective in eradicating MRSA colonization in hospitalized patients for at least 3 months.

Topics: Administration, Intranasal; Aged; Aged, 80 and over; Carrier State; Chlorhexidine; Doxycycline; Drug Therapy, Combination; Female; Hand Disinfection; Humans; Male; Methicillin Resistance; Middle Aged; Mupirocin; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a bacterial pathogen in patients with cystic fibrosis (CF) although its clinical effects can be variable. The aim of this study was to evaluate the efficacy of a three-step decolonization protocol for MRSA (Belfast CF MRSA decolonization protocol). Of the 17 paediatric patients treated during the five years of the study, eight (47%) were successfully decolonized following one five-day course of oral rifampicin and fusidic acid. The success rate increased to 12 (71%) patients after a second five-day oral treatment course in the 11 patients who remained culture positive at the end of the first treatment cycle. In a further four patients, clearance was achieved with a course of intravenous teicoplanin, increasing the decolonization rate to 16 of 17 patients (94%). These results compare favourably with other published studies and show that MRSA decolonization can be successful in a high proportion of paediatric CF patients.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Fusidic Acid; Humans; Infant; Male; Methicillin Resistance; Pneumonia; Rifampin; Severity of Illness Index; Sputum; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin

Topics: Acetamides; Adult; Aged; Anti-Infective Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hematologic Diseases; Humans; Linezolid; Male; Methicillin Resistance; Middle Aged; Oxazolidinones; Prospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Thrombocytopenia

To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia.. A prospective randomized multicentre trial from January 2000 to August 2002.. Thirteen tertiary care or university hospitals in Finland.. Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded.. Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected.. Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points.. Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54).. Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Chi-Square Distribution; Drug Therapy, Combination; Female; Finland; Humans; Levofloxacin; Male; Middle Aged; Odds Ratio; Ofloxacin; Penicillins; Prospective Studies; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

Infection is a major complication of cerebrospinal fluid (CSF) shunting procedures. Recently, rifampin-impregnated and clindamycin-impregnated silicone catheters have been developed in an attempt to prevent and/or reduce the incidence of shunt infections. In vitro and in vivo animal studies have shown their efficacy in reducing bacterial colonization of catheters. However, these shunts are yet to be evaluated in clinical trials and their safety and efficacy in preventing shunt infections is unknown.. Between April 2002 and April 2003, 31 children (age range 6 months to 17 years, mean 4.5 years) underwent implantation of an antibiotic-impregnated silicone catheter for CSF diversion. All surgeries were performed by a single neurosurgeon (HSM) at a single medical center. The Codman Hakim Bactiseal silicone catheter was used in all children. Thirty-two catheters were implanted in 31 children. All children have been followed since surgery (for an average of 19 months). For comparison, the previous 46 standard implanted shunts over a similar period of time were reviewed (average follow-up 31 months).. Of the 32 implanted catheters, 11 involved placement of a new complete shunt system, 8 were distal revisions, and 13 were proximal/ventricular revisions. There were fewer early and late complications than in the standard shunt group (12.5 and 18.8% vs. 23.9 and 34.8%). There was no local reaction from implantation of the catheters. One child contaminated his distal catheter by disrupting his abdominal incision. None of the other patients have developed any evidence of shunt infection to date.. Rifampin-impregnated and clindamycin-impregnated silicone catheters appear to be safe and well tolerated in children. Preliminary results suggest a low incidence of shunt infection. Longer follow-up and a larger number of patients are needed to more accurately assess the efficacy of these catheters compared with traditional silicone catheters.

Topics: Adolescent; Anti-Bacterial Agents; Catheterization; Cerebrospinal Fluid Shunts; Child; Child, Preschool; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Infant; Male; Retrospective Studies; Rifampin; Silicones; Staphylococcal Infections; Treatment Outcome

Oral combination therapy with fluoroquinolones plus rifampicin is a promising alternative to standard parenteral therapy for staphylococcal infections.. In a multicenter, randomized trial, we compared the efficacy, safety, and length of hospital stay for patients with staphylococcal infections treated either with an oral combination of a fluoroquinolone (fleroxacin) plus rifampicin or with standard parenteral treatment (flucloxacillin or vancomycin). Patients were included if cultures showed the presence of bacteremia or deep-seated infections with Staphylococcus aureus (104 patients) or catheter-related bacteremia due to drug-susceptible, coagulase-negative staphylococci (23 patients).. The cure rate in the intention-to-treat analysis was 78% for the fleroxacin-rifampicin group (68 patients) and 75% for the standard therapy group (59 patients; 47 received flucloxacillin, and 12 received vancomycin); in the population of clinically evaluable patients (n=119), the cure rate was 82% and 80%, respectively; and in the population of microbiologically evaluable patients (n=103), the cure rate was 86% and 84%, respectively. Clinical and bacteriological failures after S. aureus infections were documented in similar proportions of patients. The median length of hospital stay after study entry was 12 days in the fleroxacin-rifampicin group, compared with 23 days in the standard treatment group (P=.006). More adverse events probably related to the study drug were reported in the fleroxacin-rifampicin group than in the standard therapy group (15 of 68 vs. 5 of 59 patients; P=.05).. This study suggests that an oral regimen containing a fluoroquinolone plus rifampicin may be effective for treating staphylococcal infections, allowing earlier discharge from the hospital.

Topics: Administration, Oral; Adult; Aged; Bacteremia; Catheters, Indwelling; Drug Therapy, Combination; Female; Fleroxacin; Floxacillin; Humans; Male; Methicillin Resistance; Middle Aged; Prospective Studies; Rifampin; Safety; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Treatment Outcome; Vancomycin

To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure.. Between May 2000 and March 2002, 66 patients were randomly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were randomly assigned to receive an unimpregnated catheter. Patients were followed prospectively until the catheter was removed. Catheter-related infection was determined through quantitative catheter cultures, quantitative blood cultures, or both.. Both groups of patients were similar in age, sex, underlying disease, type of dialysis (continuous vs. intermittent), neutropenia during catheterization and its duration, catheter insertion difficulties, and administration of blood products or medication. The mean (+/- SD) catheter dwell time was the same in both groups (8 +/- 6 days, P = 0.7). There were seven catheter-related infections (11%), all associated with the use of unimpregnated catheters. Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection (P = 0.006).. The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antibiotics, Antitubercular; Catheterization, Central Venous; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Middle Aged; Minocycline; Polyurethanes; Prospective Studies; Renal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Time Factors

Staphylococcus species are the most common organisms responsible for infection following implantable cerebrospinal fluid (CSF) diversionary procedures. The role of an antibiotic-impregnated shunt (AIS) system in the prevention of shunt infection has remained unclear because no human clinical trial has been reported on thus far. In this study, the authors assess an AIS system with respect to its prevention of shunt infection.. Patients were prospectively randomized into groups to evaluate the efficacy of an AIS system against an identical control shunt system. The data accrued were subjected to a detailed statistical analysis. Logistic regression analysis was performed to determine the independent association between outcome and predictor variables. Shunt function analysis was also performed to compare the average time to infection between the two groups. One hundred ten patients were recruited; 60 received control shunt systems and 50 received AIS systems. Thirteen shunt infections were recorded (10 in the control group and three in the AIS group). Nine (69%) of 13 infections occurred within 2 months after shunt implantation (eight of 10 in the control group and one of three in the AIS group). Apart from one patient in whom no organism was identified, a total of 14 organisms (12 patients) were cultured from either the CSF (nine) or the shunt apparatus (three). Staphylococcus species accounted for the majority of shunt infections (83%): all 10 control shunts were found to have a positive culture of staphylococci, whereas none of the AISs had any staphylococci (p = 0.038).. The AIS afforded antistaphylococcal protection, especially during the early postoperative period when most shunt infections are known to occur and throughout the follow-up period (median 9 months). The AIS system represents another important tool to enable the neurosurgeon to prevent shunt infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Child; Child, Preschool; Clindamycin; Female; Humans; Hydrocephalus; Infant; Male; Middle Aged; Rifampin; Staphylococcal Infections

One hundred and fifty-nine cases of clinical Staphylococcus aureus mastitis were analyzed to detect factors associated with bacteriological cure after therapy. On 100 Dutch dairy farms, data were collected from four clinical trials with five intramammary treatment regimes designed to treat beta-lactamase-positive pathogens. Infected quarters were treated three times, with a 12-h interval between treatments. Treatment was extended for 2 d if results of the trial treatment were, according to the owner, not satisfactory. The overall bacteriological cure rate was 52%. The bacteriological cure rate of clinical beta-lactamase-negative S. aureus mastitis was significantly higher than that of clinical beta-lactamase-positive S. aureus mastitis. Bacteriological cure was also significantly higher if somatic cell count of the cow was low at the milk recording prior to the onset of the clinical mastitis. The bacteriological cure rate of clinical beta-lactamase-negative S. aureus mastitis was also significantly higher after an extended treatment compared with no extended treatment. The seriousness of the various clinical symptoms and the bacteriological cure rate of clinical S. aureus mastitis were not associated.

Topics: Ampicillin; Animals; Antibiotics, Antitubercular; beta-Lactam Resistance; Cattle; Cefazolin; Cephalosporins; Cloxacillin; Colistin; Double-Blind Method; Female; Mastitis, Bovine; Milk; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim

To determine the clinical role of rifampin containing antibiotic combination and modified two-stage exchange arthroplasty with a vancomycin loaded polymethylmethacrylate (PMMA) spacer for the treatment of orthopaedic implant related Staphylococcus epidermidis infections, a prospective study was initiated. A total of 10 patients, with a mean age of 59 years (range: 32 to 78 years) were included in the study. The mean follow up was 23.4 months (range: 16 to 36 months). Six patients had an infected hemiarthroplasty of the hip, three had infected total hip arthroplasty, and one had an infected femoral neck fracture with implant failure and pseudoarthrosis. All had culture-proven Staphylococcus epidermidis infections, six of the isolates were methicillin resistant. Following debridement and implantation of a PMMA spacer, a rifampin-vancomycin antibiotic protocol was initiated until the erythrocyte sedimentation rate and C-reactive protein levels were within normal limits. After reimplantation and discharge from the hospital, oral antibiotics with rifampin-ciprofloxacin were continued for three to six months. At the final follow-up none of the patients had any clinical or laboratory signs of infection. Although this study includes a limited number of patients and relatively short-term follow-up the results indicate that in the presence of orthopaedic implant infection with Staphylococcus epidermidis, modified two-stage exchange arthroplasty using a vancomycin-loaded PMMA spacer and a rifampin-containing antibiotic protocol may be beneficial.

Topics: Adult; Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Chronic Disease; Female; Follow-Up Studies; Hip Prosthesis; Humans; Male; Middle Aged; Prospective Studies; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Outcome; Vancomycin

Rifampicin has been successfully used as an adjunct to vancomycin therapy in several clinical conditions of MRSA infections such as endocarditis, ventriculoperitoneal shunts and septicaemia. However, very little information is available in the literature regarding its use in MRSA septicaemia in burns. The present prospective study was conducted to evaluate the efficacy of rifampicin as an adjunct therapy in burn cases with MRSA septicaemia not responding well to vancomycin. Fourteen out of 36 MRSA septicaemia patients with burns who either did not or only partially responded to therapeutic doses of vancomycin within 5-6 days were treated with rifampicin as an adjunct therapy (600 mg, i.v., o.d) for 5 days during the study period between January 1995 to December 1998. All the patients had burns due to flame and the TBSA varied between 20-90% with a mean of 64%. Eleven patients had deep and three had mixed burns. MRSA septicaemic episodes usually followed 2 3 days of detection of the organism in burn wounds. All the isolates were sensitive to vancomycin with an MIC of < or = 1.0 mg/L and were treated with vancomycin, (500 mg, i.v., 6 hourly). The serum vancomycin levels in all the patients were within the therapeutic range. However, blood cultures still remained positive even after 5-6 days of therapy. Institution of rifampicin, as an adjunct to vancomycin therapy to which the MRSA isolates were susceptible, showed a dramatic clinical response and survival of grafts. Thirteen patients survived and one died who had 70% deep burns and blood cultures revealed a multiresistant Acinetobacter in addition to MRSA. The present study thus confirms the efficacy of clinical use of rifampicin as an adjunct in vancomycin nonresponding cases of MRSA septicaemia in burns.

Topics: Adolescent; Adult; Bacteremia; Burn Units; Burns; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Kuwait; Male; Methicillin Resistance; Middle Aged; Prognosis; Prospective Studies; Rifampin; Staphylococcal Infections; Survival Rate; Treatment Outcome; Vancomycin

Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial.. To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices.. A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997.. Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland.. A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days).. Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy.. Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism.. A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device.. Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.

Topics: Aged; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Disease-Free Survival; Double-Blind Method; Drug Therapy, Combination; Female; Floxacillin; Hip Prosthesis; Humans; Knee Prosthesis; Male; Middle Aged; Orthopedic Fixation Devices; Penicillins; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

An open study was carried out on 16 patients with hospital-acquired, bacteraemic Staphylococcus aureus infections to evaluate the safety and efficacy of teicoplanin plus rifampicin. Patients received teicoplanin 400 mg bd for the first 24 h followed by 400 mg od thereafter, and rifampicin 600 mg bd. Both agents were given intravenously. Serum samples were collected to determine trough and peak antibiotic concentrations. The MIC of teicoplanin and rifampicin and the MBC of teicoplanin were determined for all S. aureus isolates. Time-kill curves were performed for the drugs individually and in combination. Clinical efficacy was assessed by the APACHE II scoring system. Bacteriological success was evaluated by elimination, persistence or recurrence of S. aureus. Safety was carefully monitored by regular biochemical and haematological testing and recording of adverse events. Fifteen patients were evaluable, of whom 13 (86.7%) were clinically cured with elimination of S. aureus. One patient died, but death was not attributed to the study drugs. Treatment failed in another patient who relapsed with a high fever. S. aureus was recovered from blood cultures from this patient, and resistance to rifampicin had developed. Time-kill curves all showed adequate killing of S. aureus at the drug concentrations measured in vivo. Neither synergy nor antagonism between teicoplanin and rifampicin was demonstrated. The combination of teicoplanin and rifampicin is an effective and well-tolerated treatment for bacteraemic S. aureus infections, but in deep-seated foci of infection resistance to rifampicin may develop.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Colony Count, Microbial; Cross Infection; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Treatment Outcome

The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2% applied daily to the exit site. The study design was a prospective randomized trial, controlling for S aureus nasal carriage. Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients (54% male, 71 % white, 34% insulin-dependent, mean prestudy time on peritoneal dialysis 1.2 years) were randomly assigned to cyclic rifampin (n = 41 patients) or daily exit site mupirocin prophylaxis (n = 41 patients). Mean follow-up was 1 year. S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin (P = NS). Both rates were significantly lower than the center's historical rate (the period between 1983 and 1992) of 0.46/yr prior to the study (P < 0.001). S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.16/yr (P < 0.02). Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.12/yr (P < 0.001). There were no side effects in patients using mupirocin, but 12% were unable to continue rifampin due to side effects. We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections. In addition, rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections. Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections, particularly in patients who cannot tolerate oral rifampin therapy.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Anti-Bacterial Agents; Catheters, Indwelling; Chemoprevention; Diabetes Mellitus, Type 1; Drug Administration Schedule; Equipment Contamination; Equipment Failure; Female; Follow-Up Studies; Humans; Male; Mupirocin; Nose; Ointments; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To compare the efficacy and safety of inpatient oral antibiotic treatment (oral) versus standard parenteral antibiotic treatment (intravenous) for right-sided staphylococcal endocarditis in injection drug users.. In a prospective, randomized, non-blinded trial, febrile injection drug users were assigned to begin oral or intravenous (IV) treatment on admission, before blood culture results were available. Oral therapy consisted of ciprofloxacin and rifampin. Parenteral therapy was oxacillin or vancomycin, plus gentamicin for the first 5 days. Antibiotic dosing was adjusted for renal dysfunction. Administration of other antibacterial drugs was not permitted during the treatment or follow-up periods. Bacteremic subjects having right-sided staphylococcal endocarditis received 28 days of inpatient therapy with the assigned antibiotics. Test-of-cure blood cultures were obtained during inpatient observation 6 and 7 days after the completion of antibiotic therapy, and again at outpatient follow-up 1 month later. Criteria for treatment failure and for drug toxicity were prospectively defined.. Of 573 injection drug users who were hospitalized because of a febrile illness and suspected right-sided staphylococcal endocarditis, 93 subjects (16.2%) had two or more sets of blood cultures positive for staphylococci; 85 of these bacteremic subjects (14.8%) satisfied diagnostic criteria for at least possible right-sided staphylococcal endocarditis (no other source of bacteremia was apparent) and entered the trial. Forty-four (oral, 19; IV, 25) of these 85 subjects completed inpatient treatment and evaluation including test-of-cure blood cultures. There were four treatment failures (oral, 1 [5.2%]; IV, 3 [12.0%]; not significant, Fisher's exact test). Drug toxicity was significantly more common in the parenterally treated group (oral, 3%; IV, 62%; P < 0.0001), consisting largely of oxacillin-associated increases in liver enzymes.. For selected patients with right-sided staphylococcal endocarditis, oral ciprofloxacin plus rifampin is effective and is associated with less drug toxicity than is intravenous therapy.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Endocarditis, Bacterial; Female; Gentamicins; Humans; Infusions, Intravenous; Length of Stay; Male; Oxacillin; Penicillins; Prospective Studies; Rifampin; Staphylococcal Infections; Substance Abuse, Intravenous; Treatment Outcome; Vancomycin

To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli.. Open, randomized, controlled, multicenter clinical trial.. Centers participating in the National Cancer Institute of Canada Clinical Trials Group.. 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting.. One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy.. Incidence and cause of suspected or proven infection.. Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group).. Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

Topics: Adult; Aged; Anti-Infective Agents; Antineoplastic Agents; Bacteremia; Colony Count, Microbial; Female; Humans; Male; Middle Aged; Neutropenia; Norfloxacin; Ofloxacin; Rifampin; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome

Topics: Catheterization; Drug Therapy, Combination; Humans; Long-Term Care; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Nasal Cavity; Pilot Projects; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

This study evaluates the dialysis-related infection rate in children receiving peritoneal dialysis with Staphylococcus aureus nasal carriage. Children with S. aureus nasal carriage were randomized to treatment with rifampin and bacitracin or no treatment. The children were observed for one month after randomization for evidence of a S. aureus dialysis-related infection. Individuals with nasal carriage had a higher incidence of S. aureus dialysis-related infection than those patients without carriage (p < 0.05). Those children treated for nasal carriage had a lower dialysis-related infection rate than those who were untreated (p < 0.05). We conclude that children receiving peritoneal dialysis with nasal carriage of S. aureus are at a greater risk of developing a S. aureus dialysis-related infection. The treatment of nasal carriage in this population decreased the risk of a S. aureus dialysis-related infection.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Bacitracin; Carrier State; Child; Child, Preschool; Female; Humans; Infant; Male; Nasal Cavity; Peritoneal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus

We examined the effectiveness and safety of the combination of rifampin plus ofloxacin given orally for treating prosthetic orthopedic implants infected with staphylococci. The prospective cohort study was conducted in a referral public hospital with ambulatory care services between 1985 and 1991. Consecutive patients from whom Staphylococcus organisms susceptible to the study drugs were isolated from their orthopedic implants and who had no contraindication to the treatment were eligible for the study. All patients were treated orally with rifampin, 900 mg/day, plus ofloxacin, 600 mg/day. Patients with hip prosthesis infection were treated for 6 months, with removal of any unstable prostheses after 5 months of treatment; patients with knee prosthesis infection were treated for 9 months, with removal of the prosthesis after 6 months of treatment; and patients with infected bone plates were treated for 6 months, with removal of the plate after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment and follow-up or telephone interviews were conducted at 6, 12, 24, 36, 48, and 60 months thereafter. Treatment failures were documented by clinical evaluation, sampling of the infected site for culture and antibiotic activity measurement, and fistulography, if possible. Cure was defined as the absence of clinical, biological, and radiological evidence of infection 6 months after the completion of treatment, treatment failure was defined as the absence of cure, and relapse was defined as the reappearance of infection caused by the same Staphylococcus isolate that caused the original infection, regardless of the timing of this secondary infection. Among 51 patients included in the study and evaluable for safety, 4 patients had side effects and were not evaluable for treatment effectiveness; the overall success rate was 74% among 47 patients, with a success rate of 81% for the hip prosthesis group, 69% for the knee prosthesis group, and 69% for the osteosynthesis device group. Eight treatment failures were relaxed to the isolation of a resistant bacterium. The combination of rifampin administered orally plus ofloxacin is a suitable alternative to the conventional long-term intravenous therapy for treatment of orthopedic implants infected with staphylococci.

Topics: Administration, Oral; Cohort Studies; Drug Therapy, Combination; Hip Prosthesis; Humans; Knee Prosthesis; Ofloxacin; Prospective Studies; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim-sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing both pressure and other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and ot

Topics: Adolescent; Adult; Aged; DNA, Neoplasm; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Middle Aged; Nasal Cavity; Novobiocin; Outcome Assessment, Health Care; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

The purpose of this prospective clinical study is to evaluate the role of combination chemotherapy with rifampin in the treatment of orthopedic device-related infections in which the implant could not be removed. Eleven patients with orthopedic implant-related infections due to staphylococci or streptococci were treated with the implant in situ. Each antimicrobial regimen included rifampin in combination with a beta-lactam antibiotic or ciprofloxacin. The median duration of treatment with rifampin was 86 days (range, 15-336 days) with a median follow-up of greater than 24 months after cessation of therapy. Treatment was successful for 82% of patients. Failures were associated with documented inappropriate treatment. These preliminary clinical data are supported by data from in vitro studies and animal experiments. Combination therapy with rifampin, in particular rifampin and a quinolone, should be considered for patients with orthopedic implant-related infections if the implant cannot be removed.

Topics: Adult; Aged; Aged, 80 and over; Female; Fracture Fixation, Intramedullary; Hip Prosthesis; Humans; Knee Prosthesis; Male; Middle Aged; Prospective Studies; Rifampin; Staphylococcal Infections

Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population.

Topics: Adult; Bacteriological Techniques; Catheters, Indwelling; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis.. Cohort analysis of a randomized study.. University medical center.. Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days.. Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia.. The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy.. Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.

Topics: Adult; Bacteremia; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fever; Gentamicins; Humans; Male; Methicillin Resistance; Middle Aged; Prospective Studies; Rifampin; Staphylococcal Infections; Statistics as Topic; Time Factors; Vancomycin

We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Methicillin Resistance; Rifampin; Single-Blind Method; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a five-year prospective controlled study of prophylaxis of Staphylococcus aureus nasal carriage and infection among patients in a hemodialysis unit. Carriers tended to have chronic colonization with a single phage type. S. aureus infections occurred significantly more frequently in carriers than in noncarriers and, in 93 percent of the infected carriers, were caused by the same phage type as that carried in the nares. Neither intravenous vancomycin nor topical bacitracin was found to be efficacious in eradicating nasal carriage. However, oral rifampin given for five days decreased S. aureus carriage over a one-month follow-up period, but within three months colonization of the nares recurred in most carriers, often with an S. aureus of the original phage type. Carriers were then randomly assigned to receive either rifampin or no prophylaxis. Rifampin was readministered at three-month intervals if culture of the anterior nares yielded S. aureus. Infections with S. aureus occurred significantly more frequently in carriers given no prophylaxis than in those given a full course of rifampin. S. aureus resistant to rifampin was isolated from the anterior nares of four patients, but these isolates were not implicated in any infections. The incidence of infection at the dialysis access site, skin, and soft tissue of patients on hemodialysis can be decreased by interventions directed at nasal carriage of S. aureus.

Topics: Administration, Intranasal; Anti-Bacterial Agents; Bacitracin; Bacteriophage Typing; Carrier State; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Evaluation, Preclinical; Humans; Injections, Intravenous; Nose; Prospective Studies; Random Allocation; Renal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Topics: Administration, Oral; Blood Sedimentation; Chronic Disease; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nafcillin; Neutropenia; Osteomyelitis; Random Allocation; Rifampin; Staphylococcal Infections; Time Factors

A total of 101 patients with proven Staphylococcus aureus infection were included in a double-blind, placebo-controlled study; this study compared oxacillin (12 g/day, intravenously) or vancomycin (2 g/day, intravenously) plus rifampin (1,200 mg/day, orally) with oxacillin or vancomycin plus placebo. We evaluated 65 patients. Of the patients tested, 33 received oxacillin plus rifampin (13 bacteremias), and 32 received oxacillin plus placebo (16 bacteremias). Clinical cure was achieved in 61% of the patients treated with oxacillin plus rifampin and in 56% of the patients treated with oxacillin plus placebo. Improvement was noted in 27 and 25%, respectively, and failure occurred in 9 and 18%, respectively. These differences were not statistically significant. Bacteriological failure occurred in 3 and 28%, respectively (P less than 0.05). None of the failures within the rifampin-treated group was associated with the emergence of a rifampin-resistant mutant. The rates of superinfection were similar in both groups. The geometric means of the serum bactericidal activity after 1, 6, and 11 h were, respectively, 22, 17, and 9 after treatment with oxacillin plus rifampin and 25, 3.4, and 2.3 after treatment with oxacillin plus placebo. It was suggested that the addition of rifampin to oxacillin or vancomycin might only be beneficial to severely ill patients.

Topics: Blood Bactericidal Activity; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Oxacillin; Random Allocation; Rifampin; Sepsis; Staphylococcal Infections; Vancomycin

In-vitro study of the combination of oxacillin with rifampicin has shown that a complex interaction occurs between the two drugs: a high oxacillin/rifampicin ratio was associated with antagonism, a low ratio was more likely to result in synergy--the combination acquired a higher rate of killing. Oxacillin significantly prevented or delayed the regrowth of rifampicin-resistant mutants, and antagonism for high oxacillin/rifampicin ratios only affected rifampicin-susceptible strains. The two clinical studies that we have performed suggested that the addition of rifampicin to standard treatment improved the clinical outcome of the patients with staphylococcal infections, and this was particularly true for the most severe infections. Failures were not associated with the emergence of rifampicin-resistant strains; the combination was not associated with more superinfections nor with more toxicity or intolerance. Serum bactericidal activities reflected a similar complex interaction to that observed in vitro by time-kill curves or checkerboard techniques.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mutation; Oxacillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Time Factors

Anterior nares cultures from 664 hospital personnel identified 165 (24.8%) as carriers of Staphylococcus aureus. Persistent carriers (17.8%) were identified and randomly assigned to one of four treatment groups: rifampin (600 mg once a day for 5 days), bacitracin ointment (topically applied three times a day for 10 days), combined rifampin and bacitracin, and control (no treatment). Bacitracin ointment was ineffective in eliminating S. aureus from the anterior nares and had a postreatment carrier rate equal to the control rate. Rifampin therapy caused a highly significant reduction (79%) in carriage; however, combined therapy was not as effective as treatment with rifampin alone. Of 132 strains of staphylococci isolated before and after treatment, all were susceptible to less than 0.016 micrograms of rifampin per ml. This study demonstrates that rifampin may be an effective antistaphylococcal antibiotic and could be used to control the carrier state in high-risk situations.

Topics: Adult; Bacitracin; Bacteriophage Typing; Carrier State; Humans; Microbial Sensitivity Tests; Nasal Mucosa; Rifampin; Staphylococcal Infections

Topics: Bone and Bones; Clinical Trials as Topic; Femur; Humans; Rifampin; Staphylococcal Infections; Staphylococcus; Tibia

Topics: Clinical Trials as Topic; Humans; Rifampin; Staphylococcal Infections

Topics: Biliary Tract Diseases; Cholangitis; Cholecystitis; Clinical Trials as Topic; Humans; Rifampin; Staphylococcal Infections; Sulfobromophthalein; Urinary Tract Infections

The clinical significance of rifampicin resistance in Staphylococcus aureus infections has not been demonstrated. Here, we evaluated the clinical characteristics of rifampicin-resistant S. aureus infection.. Data were collected from adult patients who were hospitalized with MRSA bacteraemia between March 2007 and May 2020 at a tertiary hospital in South Korea. The clinical characteristics and treatment outcomes of patients infected with rifampicin-resistant MRSA were compared with those of rifampicin-susceptible isolates. All-cause death and recurrence of MRSA infection were assessed for 90 days.. Of the 961 patients with MRSA bacteraemia, 61 (6.3%) were infected by rifampicin-resistant isolates. The type of infection focus and duration of bacteraemia did not significantly differ between the two groups. Rifampicin-resistant MRSA isolates were more likely to have multidrug resistance and a higher vancomycin MIC relative to the rifampicin-susceptible isolates. The 90-day recurrence rate was higher in the patients infected with rifampicin-resistant MRSA compared with those with rifampicin-susceptible MRSA (18.0% versus 6.2%, P < 0.001), whereas the 90-day mortality was comparable between the two groups (27.9% versus 29.2%, P = 0.94). After adjusting for potential confounding factors, rifampicin resistance was significantly associated with 90-day recurrence (subdistributional HR: 2.31; 95% CI: 1.05-5.10; P = 0.04).. Rifampicin-resistant MRSA isolates showed distinct microbiological features in terms of multidrug resistance and a high vancomycin MIC. Although the management of MRSA bacteraemia was not significantly different between the two groups, recurrence was significantly more common in the rifampicin-resistant group. Rifampicin resistance may play a significant role in infection recurrence.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Vancomycin

Intracellular bacteria serve as a problematic source of infection due to their ability to evade biological immune responses and the inability for conventional antibiotics to efficiently penetrate cellular membranes. Subsequently, new treatment approaches are urgently required to effectively eradicate intracellular pathogens residing within immune cells (e.g. macrophages). In this study, the poorly soluble and poorly permeable antibiotic, rifampicin, was re-purposed via micro-encapsulation within inulin-lipid hybrid (ILH) particles for the treatment of macrophages infected with small colony variants of Staphylococcus aureus (SCV S. aureus). Rifampicin-encapsulated ILH (Rif-ILH) microparticles were synthesized by spray drying a lipid nano-emulsion, with inulin dissolved throughout the aqueous phase and rifampicin pre-loaded within the lipid phase. Rif-ILH were strategically designed and engineered with pH-responsive properties to promote lysosomal drug release upon cellular internalization, while preventing premature rifampicin release in plasma-simulating media. The pH-responsiveness of Rif-ILH was controlled by the acid-mediated hydrolysis of the inulin coating, where exposure to acidic media simulating the lysosomal environment of macrophages triggered hydrolysis of the oligofructose chain and the subsequent diffusion of rifampicin from Rif-ILH. This pH-provoked release mechanism, as well as the ability for ILH microparticles to be more readily internalized by macrophages, was found to be influential in triggering a 2.9-fold increase in intracellular rifampicin concentration within infected macrophages, compared to the pure drug. The subsequent increase in exposure of intracellular pathogens to rifampicin leads to a ~ 2-log improvement in antibacterial activity for Rif-ILH, at a rifampicin dose of 2.5 µg/mL. Thus, the reduction in viability of intracellular SCV S. aureus, in the absence of cellular toxicity, is indicative of ILH microparticles serving as a unique approach for the safe and efficacious delivery of antibiotics to phagocytic cells for the treatment of intracellular infections.

Topics: Anti-Bacterial Agents; Humans; Hydrogen-Ion Concentration; Inulin; Lipids; Macrophages; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Methicillin-resistant. This retrospective study was conducted from January 2016-December 2021 on patients at eleven ISPED-group hospitals.. From 2016-2021, a total of 13024 MRSA isolates were obtained from children. The most common age group for patients with MRSA infection was less than 3 years old, and newborns were an important group affected by MRSA infection. MRSA was most commonly isolated from the lower respiratory, an abscess, a secretion, or blood in neonates and from the lower respiratory, an abscess, or the upper respiratory in non-neonates. All isolates were susceptible to vancomycin and linezolid and resistant to penicillin; additionally, 76.88%, 54.97%, 22.30%, 5.67%, 5.14%, 3.63%, and 1.42% were resistant to erythromycin, clindamycin, tetracycline, levofloxacin, sulfamethoxazole-trimethoprim (TMP-SMX), gentamicin, and rifampin, respectively. Between 2016 and 2021, a significant increase was seen in the levofloxacin- and TMP-SMX-resistance rates (from 5.45% to 7.14% and from 4.67% to 6.50%, respectively) among MRSA isolates, along with a significant decrease in the rates of resistance to erythromycin (from 82.61% to 68.08%), clindamycin (from 60.95% to 46.82%), tetracycline (from 25.37% to 17.13%), gentamicin (from 4.53% to 2.82%), and rifampin (from 1.89% to 0.41%).. The antibiotic-resistance rates varied among MRSA isolated from different sources. Because of the high antibiotic resistance rate to clindamycin, this antibiotic is not recommended for empirical treatment of MRSA infections, especially in osteomyelitis.

Topics: Abscess; Anti-Bacterial Agents; Child; Child, Preschool; Clindamycin; Communicable Diseases; Drug Resistance, Bacterial; Erythromycin; Gentamicins; Humans; Infant, Newborn; Levofloxacin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices.. A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient's symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72.. To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Topics: Adolescent; Anti-Bacterial Agents; Child; Coagulase; Cross Infection; Hospitals; Humans; Linezolid; Male; Meningitis, Bacterial; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus haemolyticus; Vancomycin

Strong biofilm production in

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Biofilms; Humans; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis

Topics: Anti-Bacterial Agents; Endocarditis; Endocarditis, Bacterial; Humans; Linezolid; Rifampin; Staphylococcal Infections

We measured antibiotic penetration and bioavailability in staphylococcus biofilms using simulated humanized concentrations of fluorescent vancomycin plus or minus rifampin. Vancomycin percent recovery across biofilm layers was:upper = 46%, middle = 40%, and lower = 33%. Vancomycin plus rifampin was not significantly different (P = 0.65). Addition of rifampin did not improve vancomycin penetration across biofilm layers.

Topics: Anti-Bacterial Agents; Biofilms; Biological Availability; Humans; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Vancomycin

Topics: Anti-Bacterial Agents; Humans; Orthopedic Procedures; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis

We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.. Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration.. All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24).. We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.

Topics: Animals; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Rats; Rifampin; Staphylococcal Infections; Tissue Plasminogen Activator; Vancomycin

Rifampicin plays a key role in the management of prosthetic joint infections (PJIs), however, the emergence of rifampicin resistance is associated with less favourable clinical outcomes. The purpose of this study was to investigate the impact of rifampicin resistance and other patient-related factors on recovery rates among patients with PJI undergoing debridement, antibiotics and implant retention (DAIR).. We reviewed medical records and microbiology reports of 67 patients (37 males and 30 females) undergoing DAIR due to PJI between 2014 and 2021. Patient-related factors, co-morbidities and microbiological reports were collected and reviewed. Forty-four patients had hip, 21 had knee, 1 had shoulder and 1 had elbow joint infection. Obtained data were statistically analysed with a logistic regression model.. Rifampicin-sensitive organism was isolated in 47 cases. Recovery rate was 72.3% in the sensitive and 76.9% in the resistant group. We found no significant effect of rifampicin resistance on the probability of recovery. Age and diabetes mellitus showed negative clinical impact on recovery. Staphylococcus aureus and coagulase-negative Staphylococci were predominant in the rifampicin-sensitive (66.6% of the isolates) and Gram-negative rods in the resistant group (65.2%).. Based on our results, higher age and diabetes mellitus may have a clinically relevant negative impact on clinical outcome, however, this effect was not statistically significant. This may be due to the limited number of patients included in this study. We observed no clinically relevant effect of rifampicin-resistance, sex and body mass index (BMI) on recovery rates among patients undergoing DAIR due to PJI.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Female; Humans; Male; Rifampin; Risk Factors; Staphylococcal Infections

Staphylococci are among the list of problematic bacteria contributing to the global antibiotic resistance (ABR) crisis. Their ability to adopt the small colony variant (SCV) phenotype, induced by prolonged antibiotic chemotherapy, complicates staphylococcal infection control options. Novel and alternative approaches are needed to tackle staphylococcal infections and curb ABR. Manuka honey (MH), a non-antibiotic alternative is recognized for its unique antibacterial activity based on its methylglyoxal (MGO) component.. In this study, MH (MGO 830+) was tested in combination with gentamicin (GEN), rifampicin (RIF), or vancomycin (VA) against staphylococcal wildtype (WT) and SCVs. To our knowledge, there are no current studies in the literature documenting the effects of MH on staphylococcal SCVs. While. The three staphylococci were most susceptible to RIF (0.06-0.24 μg/ml), then GEN (0.12-0.49 μg/ml), and lastly VA (0.49-0.96 μg/ml). The MICs of MH were 7%, 7-8%, and 6-7% (w/v), respectively. Fractional inhibitory concentration (FIC) evaluations showed that the combined MH + antibiotic effect was either additive (FICI 1-2), or partially synergistic (FICI >0.5-1). While all three antibiotics induced SCVs

Topics: Anti-Bacterial Agents; Gentamicins; Honey; Humans; Magnesium Oxide; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis

To demonstrate the in vitro activity of orally available antibiotics against Staphylococcus aureus isolated from bone or orthopedic implant materials. The biofilm eradication of the combination of three antibiotics was also assessed.. Clinical isolates from orthopedic infection samples were collected, and S. aureus isolates were classified according to their biofilm production and composition. Almost all S. aureus isolates (n = 36, 97.3%) produced biofilm and the major biofilm components were polysaccharides. Antimicrobial susceptibility was determined in planktonic (minimal inhibitory concentration; MIC) and biofilm cells (minimal biofilm eradication concentration; MBEC) using the MBEC Calgary Device. Overall, the MBEC ranged higher than the MIC. When combined at borderline-susceptible concentrations, moxifloxacin-rifampin and doxycycline-rifampin were both able to eradicate biofilms in a third of the strains whereas the doxycycline-moxifloxacin combination proved ineffective at eradicating biofilm, inhibiting it only in three strains.. We propose rifampin in combination with moxifloxacin or doxycycline for the design of clinical trials of bone and/or orthopedic device infection without proper debridement or material retention.

Topics: Anti-Bacterial Agents; Biofilms; Doxycycline; Humans; Microbial Sensitivity Tests; Moxifloxacin; Plankton; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Methicillin-sensitive

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactams; Biofilms; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Clindamycin; Humans; Rifampin; Staphylococcal Infections

A set of structurally related diphenylurea derivatives bearing aminoguanidine moiety were synthesized, and their antibacterial activity was assessed against a panel of multi-drug resistant Gram-positive clinical isolates. Two compounds 6 and 24 were identified with better bacteriological profile than the lead compound I. The multi-step resistance development studies indicated that MRSA are less likely to develop resistance toward diphenylurea compounds. Moreover, these compounds demonstrated a prolonged post-antibiotic effect than that of vancomycin. Furthermore, compounds 6 and 24 were able to re-sensitize VRSA to vancomycin, resulting in 8- to more than 32-fold improvement in vancomycin MIC values against clinical VRSA isolates. Finally, when assessed in an in vivo skin infection mouse model, the efficacy of compound 24 was very comparable to that of the commercially available fusidic acid ointment. Additionally, the diphenylurea 24 did not have a pronounced effect on the animal weights along the experiment indicating its safety and tolerability to mice. Taken together, these results indicate that the diphenylurea scaffold merits further investigation as a promising anti-staphylococcal treatment option.

Topics: Animals; Anti-Bacterial Agents; Methicillin; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship; Vancomycin; Vancomycin-Resistant Staphylococcus aureus

The genus

Topics: Animals; Anti-Bacterial Agents; Artocarpus; Biofilms; Flavonoids; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group.. This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards.. A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects.. Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation.

Topics: Adult; Anti-Bacterial Agents; Child; Clindamycin; Cystic Fibrosis; Fusidic Acid; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Staphylococci account for approximately 60% of periprosthetic joint infections (PJIs). Rifampicin (RMP) combination therapy is generally considered to be the treatment of choice for staphylococcal PJIs but carries an important risk of adverse events and drug-drug interactions. Rifabutin (RFB) shares many of the properties of rifampicin but causes fewer adverse events.. To compare the minimal inhibitory concentration (MIC), the minimum bactericidal concentrations (MBC), and the minimum biofilm eradication concentrations (MBEC) of rifabutin and rifampicin for staphylococcal clinical strains isolated from PJIs.. 132 clinical strains of rifampicin-susceptible staphylococci [51 Staphylococcus aureus (SA), 48 Staphylococcus epidermidis (SE) and 33 other coagulase-negative staphylococci (CoNS)] were studied. The MBC and the MBEC were determined using the MBEC® Assay for rifabutin and rifampicin and were compared.. When compared with the rifampicin MIC median value, the rifabutin MIC median value was significantly higher for SA (P < 0.05), but there was no statistically significant difference for SE (P = 0.25) and CoNS (P = 0.29). The rifabutin MBC median value was significantly higher than that of rifampicin for SA (P = 0.003) and was lower for SE (P = 0.003) and CoNS (P = 0.03). Rifabutin MBEC median value was statistically lower than that of rifampicin for all strains tested.. Using the determination of MBEC values, our study suggests that rifabutin is more effective than rifampicin against clinical strains of Staphylococcus spp. obtained from PJIs. Using MBECs instead of MICs seems to be of interest when considering biofilms. In vivo higher efficacy of rifabutin when compared with rifampicin needs to be confirmed.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Microbial Sensitivity Tests; Rifabutin; Rifampin; Staphylococcal Infections; Staphylococcus

Difficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown.. We plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics.. The extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13-19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance.. Colony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines.

Topics: Agar; Anti-Bacterial Agents; Biofilms; Humans; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Infections of orthopaedic implants, such as fracture fixation devices and total-joint prostheses, are devastating complications. Staphylococcus aureus (S. aureus) is a predominant pathogen causing orthopaedic-implant biofilm infections that can also internalise and persist in osteoblasts, thus resisting antibiotic therapy. Bacteriophages are a promising alternative treatment approach. However, data on the activity of bacteriophages against S. aureus, especially during intracellular growth, and against in vivo biofilm formation on metals are scarce. Therefore, the present study evaluated the in vitro efficacy of S. aureus bacteriophage 191219, alone as well as in combination with gentamicin and rifampicin, to eradicate S. aureus strains in their planktonic stage, during biofilm formation and after internalisation into osteoblasts. Further, the invertebrate model organism Galleria mellonella was used to assess the activity of the bacteriophage against S. aureus biofilm on metal implants with and without antibiotics. Results demonstrated the in vitro efficacy of bacteriophage 191219 against planktonic S. aureus. The phage was also effective against in vitro S. aureus biofilm formation in a dose-dependent manner and against S. aureus internalised in an osteoblastic cell line. Transmission electron microscopy (TEM) analysis showed bacteriophages on S. aureus inside the osteoblasts, with the destruction of the intracellular bacteria and formation of new bacteriophages. For the Galleria mellonella infection model, single administration of phage 191219 failed to show an improvement in survival rate but appeared to show a not statistically significant enhanced effect with gentamicin or rifampicin. In summary, bacteriophages could be a potential adjuvant treatment strategy for patients with implant-associated biofilm infections.

Topics: Anti-Bacterial Agents; Bacteriophages; Biofilms; Gentamicins; Humans; Plankton; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Osteomyelitis; Polyesters; Rats; Rifampin; Silicates; Silicon Dioxide; Staphylococcal Infections; Staphylococcus aureus

Topics: Humans; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

This case series describes seven patients who received rifabutin in place of rifampin combined with conventional antimicrobial therapy for treatment of hardware-associated staphylococcal infections. Infection recurrence, defined as need for unplanned surgical intervention within the evaluable follow up period after starting rifabutin, occurred in two patients. Two patients experienced possible treatment-associated adverse effects. Findings support future work to examine rifabutin use, when rifampin is not suitable, for adjunctive treatment of staphylococcal hardware infections.

Topics: Anti-Bacterial Agents; Drug Interactions; Humans; Rifabutin; Rifampin; Staphylococcal Infections

Biofilms protect bacteria from the host immune system and many antibiotics, making the treatment of orthopaedic infections difficult. Halicin, a recently discovered antibiotic, has potent activity against nonorthopaedic infections in mice and the planktonic, free-living forms of many bacterial species, including Staphylococcus aureus , a common cause of orthopaedic infections. Importantly, halicin did not induce resistance in vitro and was effective against drug-resistant bacteria and proliferating and quiescent bacteria. Quiescence is an important cause of antibiotic tolerance in biofilms. However, whether halicin acts on biofilms has not been tested.. (1) Does halicin reduce the viability of S. aureus in less mature and more mature biofilms as it does in planktonic cultures? (2) How do the relative effects of halicin on S. aureus biofilms and planktonic cultures compare with those of conventional antibiotics (tobramycin, cefazolin, vancomycin, or rifampicin) that are commonly used in clinical orthopaedic infections?. To measure minimal biofilm eradication concentrations (MBECs) with less mature 3-day and more mature 7-day biofilms, we used 96-well peg plates that provided high throughput and excellent reproducibility. After S. aureus -Xen36 biofilm formation, planktonic bacteria were removed from the cultures, and the biofilms were exposed to various concentrations of halicin, tobramycin, cefazolin, vancomycin, or rifampicin for 20 hours. Biofilm viability was determined by measuring resazurin reduction or by counting colony-forming units after sonication. To determine effects of halicin and the conventional antibiotics on biofilm viability, we defined MBEC 75 as the lowest concentration that decreased viability by 75% or more. To determine effects on bacterial viability in planktonic cultures, minimum inhibitory concentrations (MICs) were determined with the broth dilution method. Each result was measured in four to 10 independent experiments.. We found no differences between halicin's effectiveness against planktonic S. aureus and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 25 μM [interquartile range 25 to 25 and 25 to 25, respectively]; p > 0.99). Halicin was eightfold less effective against more mature 7-day biofilms (MBEC 75 = 200 μM [100 to 200]; p < 0.001). Similarly, tobramycin was equally effective against planktonic culture and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 20 μM [20 to 20 and 10 to 20, respectively]; p > 0.99). Tobramycin's MBEC 75 against more mature 7-day biofilms was 320 μM (320 to 480), which is 16-fold greater than its planktonic MIC (p = 0.03). In contrast, the MBEC 75 for cefazolin, vancomycin, and rifampicin against more mature 7-day biofilms were more than 1000-fold (> 1000; p < 0.001), 500-fold (500 to 875; p < 0.001), and 3125-fold (3125 to 5469; p = 0.004) greater than their planktonic MICs, respectively, consistent with those antibiotics' relative inactivity against biofilms.. Halicin was as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but eightfold higher concentrations were needed for more mature 7-day biofilms. Tobramycin, an antibiotic whose effectiveness depends on biofilm maturity, was also as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but 16-fold higher concentrations were needed for more mature 7-day biofilms. In contrast, cefazolin, vancomycin, and rifampicin were substantially less active against both less and more mature biofilms than against planktonic cultures.. Halicin is a promising antibiotic that may be effective against S. aureus osteomyelitis and infections on orthopaedic implants. Future studies should assess the translational value of halicin by testing its effects in animal models of orthopaedic infections; on the biofilms of other bacterial species, including multidrug-resistant bacteria; and in combination therapy with conventional antibiotics.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Cefazolin; Mice; Microbial Sensitivity Tests; Reproducibility of Results; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Thiadiazoles; Tobramycin; Vancomycin

Fracture healing is impaired in the setting of infection, which begets protracted inflammation. The most problematic causative agent of musculoskeletal infection is methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that modulation of excessive inflammation combined with cell-penetrating antibiotic treatments facilitates fracture healing in a murine MRSA-infected femoral fracture model. Sterile and MRSA-contaminated open transverse femoral osteotomies were induced in 10-week-old male C57BL/6 mice and fixed via intramedullary nailing. In the initial therapeutic cohort, empty, vancomycin (V), rifampin (R), vancomycin-rifampin (VR), or vancomycin-rifampin-trametinib (VRT) hydrogels were applied to the fracture site intraoperatively. Rifampin was included because of its ability to penetrate eukaryotic cells to target intracellular bacteria. Unbiased screening demonstrated ERK activation was upregulated in the setting of MRSA infection. As such, the FDA-approved mitogen-activated protein kinase kinase (MEK)1-pERK1/2 inhibitor trametinib was evaluated as an adjunctive therapeutic agent to selectively mitigate excessive inflammation after infected fracture. Two additional cohorts were created mimicking immediate and delayed postoperative antibiotic administration. Systemic vancomycin or VR was administered for 2 weeks, followed by 2 weeks of VRT hydrogel or oral trametinib therapy. Hematologic, histological, and cytokine analyses were performed using serum and tissue isolates obtained at distinct postoperative intervals. Radiography and micro-computed tomography (μCT) were employed to assess fracture healing. Pro-inflammatory cytokine levels remained elevated in MRSA-infected mice with antibiotic treatment alone, but increasingly normalized with trametinib therapy. Impaired callus formation and malunion were consistently observed in the MRSA-infected groups and was partially salvaged with systemic antibiotic treatment alone. Mice that received VR alongside adjuvant MEK1-pERK1/2 inhibition displayed the greatest restoration of bone and osseous union. A combinatorial approach involving adjuvant cell-penetrating antibiotic treatments alongside mitigation of excessive inflammation enhanced healing of infected fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).

Topics: Animals; Anti-Bacterial Agents; Cytokines; Femoral Fractures; Fracture Healing; Inflammation; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Rifampin; Staphylococcal Infections; Vancomycin; X-Ray Microtomography

Although several clinical variables have been reported as risk factors for recurrence of Staphylococcus aureus infection, most studies have not considered competing risk events that may overestimate the risk. In this study, we performed competing risk analysis to identify risk factors related to 90-day recurrence in patients with S. aureus bacteremia (SAB) using a large cohort data from a single tertiary hospital in South Korea. All adults who experienced SAB during admission were prospectively enrolled from August 2008 to December 2019. After the day of the first positive blood culture, recurrence and all-cause mortality were assessed for 90 days. Recurrence was defined as a development of symptoms or signs of infection with or without repeated bacteremia after >7 days of negative blood culture and clinically apparent improvement. Subdistribution hazard ratios (sHR) for recurrence and all-cause mortality were estimated using Fine and Gray models. Of 1,725 SAB patients, including 885 cases (51.3%) of methicillin-resistant S. aureus (MRSA) bacteremia, 85 (5.0%) experienced recurrence during the study period. In a multivariate Fine and Gray regression model, the presence of a vascular graft (subdistribution HR [sHR], 3.48; 95% confidence interval [CI], 1.90-6.40), nasal MRSA carriage (sHR, 2.10; 95% CI, 1.28-3.44), methicillin resistance (sHR, 1.69; 95% CI, 1.00-2.84), and rifampicin resistance (sHR, 2.20; 95% CI, 1.12-4.33) were significantly associated with 90-day recurrence. In a large cohort of SAB patients with a high prevalence of MRSA, indwelling vascular graft, nasal MRSA carriage, methicillin resistance, and rifampicin resistance were potential risk factors for recurrence of S. aureus infection.

Topics: Adult; Bacteremia; Humans; Methicillin-Resistant Staphylococcus aureus; Reinfection; Rifampin; Risk Assessment; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB).. A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021.. A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks.. This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

Topics: Anti-Bacterial Agents; Bacteremia; Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surveys and Questionnaires

This study aimed to study the application value of a new multichannel sensor in pathogen detection and drug resistance analysis of neonatal pneumonia. 180 newborns with infectious pneumonia were selected, and a new multichannel piezoelectric sensor was constructed. The traditional Kirby-Bauer (K-B) method and the piezoelectric sensor were adopted to detect the pathogens and drug resistance in newborn samples, respectively. The results showed that the sensitivity and specificity under the K-B method (99.58% and 99.32%) and the multichannel piezoelectric sensor (99.43% and 94.29%) were not statistically different (

Topics: Chloramphenicol; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Infant, Newborn; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Levofloxacin and rifampicin are the preferred treatment for prosthetic joint infection (PJI) caused by Staphylococcus aureus, especially when managed with implant retention (DAIR). However, a significant variability of success has been reported, which could be related to intrinsic characteristics of the microorganism. Our aim was to evaluate the variability in the anti-biofilm response to levofloxacin and rifampicin in a clinical collection of S. aureus.. Eleven levofloxacin- and rifampicin-susceptible S. aureus isolates causing PJI managed with DAIR were included. Levofloxacin, rifampicin and levofloxacin + rifampicin were tested in an in vitro static biofilm model in microtitre plates, where 48 h biofilms were challenged with antimicrobials during 24 h. Additionally, two genetically similar strains were tested in the CDC Biofilm Reactor, where 48 h biofilms were treated during 56 h. Antimicrobial activity was assessed by viable biofilm-embedded cells recount, and by crystal violet staining.. All antimicrobial regimens showed significant anti-biofilm activity, but a notable scattering in the response was observed across all strains (inter-strain coefficient of variation for levofloxacin, rifampicin and levofloxacin + rifampicin of 22.8%, 35.8% and 34.5%, respectively). This variability was tempered with the combination regimen when tested in the biofilm reactor. No correlation was observed between the minimal biofilm eradicative concentration and the antimicrobial activity. Recurrent S. aureus isolates exhibited higher biofilm-forming ability compared with strains from resolved infections (7.6 log10 cfu/cm2±0.50 versus 9.0 log10 cfu±0.07).. Significant variability may be expected in response to levofloxacin and rifampicin among biofilm-embedded S. aureus. A response in the lower range, together with other factors of bad prognosis, could be responsible of treatment failure.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Biofilms; Humans; Levofloxacin; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Compared to the clinical sector, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the food sector is relatively low. However, their presence in seafood is a significant public health concern. In India, fish and fishery products are maximally manually handled compared to other food products. In this study, 498 fish samples were collected under various conditions (fresh, chilled or dressed) and representatives from their surroundings. These samples were screened for the prevalence of Staphylococcus aureus, determining its antimicrobial resistance, MRSA and genetic profile. It is observed that 15.0% and 3.0% of the total samples were screened positive for S. aureus and MRSA, respectively. The S. aureus strain MRSARF-10 showed higher resistance to linezolid, co-trimoxazole, cefoxitin, ofloxacin, gentamicin, rifampicin, ampicillin/sulbactam and Piperacillin-tazobactam. This MRSA, spa type t021 and SCCmec type V strain isolated from dried ribbon fish (Family Trachipteridae) carried virulence factors for exoenzymes such as aureolysin, serine, toxin genes and a novel MLST ST 243, as revealed from its draft-genome sequence. This highly pathogenic, multidrug-resistant and virulent S. aureus novel strain is circulating in the environment with chances of spreading among the seafood workers and the environment. It is further suggested that Good Hygienic Practices recommended by World Health Organization need to be followed during the different stages of seafood processing to provide pathogen-free fish and fishery products to the consumers.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cefoxitin; Gentamicins; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Multilocus Sequence Typing; Ofloxacin; Piperacillin; Prevalence; Rifampin; Seafood; Serine; Staphylococcal Infections; Staphylococcus aureus; Sulbactam; Tazobactam; Trimethoprim, Sulfamethoxazole Drug Combination; Virulence Factors

Infants are at risk of Staphylococcus aureus (S. aureus) colonization and infection. The aim of this study was to investigate S. aureus and methicillin-resistant S. aureus (MRSA) colonization among infants, including the prevalence, predictors of colonization, and antibiogram.. The study was cross-sectional, and involved infants aged less than one year recruited at the Princess Marie Louise Children's Hospital in Accra, Ghana. Sociodemographic and clinical data of the participants were gathered with a structured questionnaire. Nasal swabs were also obtained from them and bacteriologically cultured. S. aureus was confirmed with the coagulase test, and MRSA was confirmed by polymerase chain reaction (PCR) of the mecA gene. Antimicrobial susceptibility testing of S. aureus was done using the Kirby-Bauer method.. The carriage prevalence of S. aureus and MRSA were 34.9% (45/129) and 17.10% (22/129), respectively. Colonization with coagulase-negative Staphylococci (CoNS) was protective of both S. aureus (OR = 0.008; p < 0.001) and MRSA (OR = 0.052; p = 0.005) carriage. Maintenance of good hand hygiene prevented S. aureus carriage (OR = 0.16; p < 0.001). S. aureus resistance to antibiotics decreased across penicillin (96%), trimethoprim-sulfamethoxazole (61%), tetracycline (61%), erythromycin (39%), gentamicin (39%), fusidic acid (26%), rifampicin (17%), clindamycin (7%), and linezolid (0%); 68.8% S. aureus were multidrug resistant.. S. aureus and MRSA prevalence were high among the infants. Colonization with CoNS and good hand hygiene maintenance were predictive of MRSA and methicillin-sensitive S. aureus (MSSA) colonization, respectively.

Topics: Anti-Bacterial Agents; Clindamycin; Coagulase; Cross-Sectional Studies; Erythromycin; Fusidic Acid; Gentamicins; Ghana; Hospitals; Humans; Infant; Linezolid; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prevalence; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital.. A descriptive study.. Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021.. Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed.. A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin.. The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections.. Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

Topics: Agar; Amikacin; Animals; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Female; Furunculosis; Humans; Impetigo; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rifampin; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Teicoplanin; Vancomycin

Topics: Humans; Rifampin; Staphylococcal Infections; Staphylococcus

The Staphylococcus aureus can switch to a transient genotype-invariant dormancy, known as a persister, to survive treatment with high doses of antibiotics. This transient persister is an important reason underlying its resistance. There is an urgent need to find new antibacterial agents capable of eradicating methicillin-resistant S. aureus (MRSA) persisters. In this study, 37 new derivatives of cajaninstilbene acid (CSA) were designed and synthesized, and their biological activity against MRSA persisters was evaluated. Most of the newly synthesized derivatives exhibit more potent antimicrobial properties against S. aureus and MRSA than CSA itself, and 23 of the 37 derivatives show a tendency to eradicate MRSA persisters. A representative compound (A6) was demonstrated to target bacterial cell membranes. It eradicated the adherent biofilm of MRSA in a concentration dependent manner, and showed a synergistic antibacterial effect with piperacilin. In a model mouse abscess caused by MRSA persisters, A6 effectively reduced the bacterial load in vivo. These results indicate that A6 is a potential candidate for treatment of MRSA persister infections.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Cell Survival; Cell Wall; Disease Models, Animal; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; RAW 264.7 Cells; Salicylates; Skin Diseases; Staphylococcal Infections; Staphylococcus aureus; Stilbenes; Structure-Activity Relationship

To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance.. This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method.. The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01).. The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carrier State; Clindamycin; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fusidic Acid; Gentamicins; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Nasal Cavity; Norfloxacin; Penicillins; Rifampin; Staphylococcal Infections; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Dalbavancin is a novel glycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It is characterized by a potent activity against numerous Gram-positive pathogens, a long elimination half-life and a favorable safety profile. Most recently, its application for the treatment of periprosthetic joint infections (PJIs) was introduced. The aim of this study was to proof our hypothesis, that dalbavancin shows superior efficacy against staphylococcal biofilms on polyethylene (PE) disk devices compared with vancomycin and additive behavior in combination with rifampicin. Staphylococcus aureus biofilms were formed on PE disk devices for 96 h and subsequently treated with dalbavancin, vancomycin, rifampicin and dalbavancin-rifampicin combination at different concentrations. Quantification of antibacterial activity was determined by counting colony forming units (CFU/ml) after sonification of the PE, serial dilution of the bacterial suspension and plating on agar-plates. Biofilms were additionally life/dead-stained and visualized using fluorescence microscopy. Dalbavancin presented superior anti-biofilm activity compared to vancomycin. Additive effects of the combination dalbavancin and rifampicin were registered. Dalbavancin combined with rifampicin presents promising anti-biofilm activity characteristics in vitro. Further in vivo studies are necessary to establish recommendations for the general use of dalbavancin in the treatment of PJIs.

Topics: Agar; Anti-Bacterial Agents; Biofilms; Drug Synergism; Glycopeptides; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Microscopy, Fluorescence; Polyethylene; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Stem Cells; Teicoplanin; Vancomycin

International guidelines recommend rifampin-based combinations for staphylococcal prosthetic valve endocarditis (PVE). However, no robust clinical data support this recommendation, and rifampin tolerability is an issue. We aimed to evaluate the impact of rifampin for the treatment of staphylococcal PVE.. An observational retrospective cohort study of all adults with staphylococcal PVE (modified Duke criteria) was conducted in 3 referral centers for endocarditis, during years 2000-2018. Primary outcome measurement was 1-year mortality.. We enrolled 180 patients with PVE due to Staphylococcus aureus (n = 114, 63.3%), or coagulase-negative staphylococci (n = 66, 36.7%), on bioprosthesis (n = 111, 61.7%), mechanical valve (n = 67, 37.2%), or both (n = 2). There were 132 males (73.3%), and mean age was 70.4 ± 12.4 years. Valvular surgery was performed in 51/180 (28.3%) cases. Despite all isolates were susceptible to rifampin, only 101 (56.1%) were treated with rifampin, for a median duration of 33.0 days, whereas 79 (43.9%) received no rifampin. Baseline characteristics were similar in both groups. One-year mortality was, respectively, 37.6% (38/101), and 31.6% (25/79), in patients treated with, or without, rifampin (P = .62). Relapse rates were 5.9% (6/101), and 8.9% (7/79), P = .65. Patients treated with rifampin had longer hospital length-of-stay: 42.3 ± 18.6 vs 31.3 ± 14.0 days (P < .0001). On multivariate analysis, only cerebral emboli (odds ratio [OR] 2.95, 95% confidence interval [CI], 1.30-6.70, P = .009), definite endocarditis (OR 7.15, 95% CI, 1.47-34.77, P = .018), and methicillin-resistant S. aureus (OR 6.04, 95% CI, 1.34-27.26, P = .019), were associated with 1-year mortality.. A large proportion (43.9%) of staphylococcal PVE received no rifampin. One-year survival and relapse rates were similar in patients treated with or without rifampin.

Topics: Adult; Aged; Aged, 80 and over; Endocarditis; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections

The objective of this study was to evaluate the clinical outcomes and safety of clindamycin combination antibiotherapy for the treatment of erythromycin-resistant, lincosamide-susceptible bone and joint infections caused by Staphylococcus spp. Between January 2010 and September 2018, 46 patients with Staphylococcus spp. erythromycin-resistant, lincosamide-susceptible bone and joint infections were treated with clindamycin combination antibiotherapy for 6 to 12 weeks. The type of infection was prosthetic in 20 cases (43.5%), osteosynthetic device in 15 cases (32.6%), chronic osteomyelitis in 7 cases (15.2%), and arthritis in 4 cases (8.7%). The cure rate was 67.4% by intention to treat and 84.6% per protocol, with a median follow-up of 398 days (range 86-843). Only 2 relapses (5.1%) were observed in patients with chronic osteomyelitis; an acquired resistance to lincosamides developed in 1 case. Clindamycin combination therapy appears to be effective for the treatment of bone and joint infection caused by erythromycin-resistant, lincosamide-susceptible Staphylococcus spp.

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Clindamycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Erythromycin; Female; Humans; Joints; Male; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus

Topics: Animals; Antibiotics, Antitubercular; Bacterial Load; Drug Evaluation, Preclinical; Fracture Healing; Fractures, Open; Hydrogels; Male; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred C57BL; Osteomyelitis; Rifampin; Staphylococcal Infections

After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy.. Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-L-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-L-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones.. Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.

Topics: Anti-Bacterial Agents; Biofilms; Drug Delivery Systems; Drug Liberation; Lactic Acid; Microbial Sensitivity Tests; Nanoparticles; Polyesters; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surface Properties

Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared.

Topics: Anti-Bacterial Agents; Blood Cells; Blood Vessel Prosthesis; Delayed-Action Preparations; Dipyridamole; Drug Delivery Systems; Drug Liberation; Equipment Design; Human Umbilical Vein Endothelial Cells; Humans; Platelet Aggregation Inhibitors; Polyurethanes; Printing, Three-Dimensional; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Technology, Pharmaceutical; Thrombosis

Infective endocarditis is associated with a variety of clinical signs, but its association with multisystem vasculitis is rarely reported. A high index of suspicion is necessary to differentiate a primary autoimmune vasculitis from an infectious cause as the wrong treatment can lead to significant morbidity and mortality. We present a 71-year-old female patient with negative blood cultures, on antibiotics for recent bacteraemia, who presented with cutaneous and renal leucocytoclastic vasculitis. Workup revealed a vegetation adjacent to her right atrial pacemaker lead consistent with infective endocarditis and her vasculitis completely resolved with appropriate antibiotics.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Bacteremia; Ceftriaxone; Endocarditis, Bacterial; Female; Humans; Pulmonary Edema; Renal Dialysis; Respiratory Insufficiency; Rifampin; Skin Diseases, Vascular; Staphylococcal Infections; Vasculitis

Prosthetic joint infections (PJI) are a major cause of morbidity and mortality burden worldwide. While surgical management is well defined, rifampicin (RIF) dose remains controversial. The aim of our study was to determine whether Rifampicin dose impact infection outcomes in PJI due to Staphylococcus spp.. single-center retrospective study including 411 patients with PJI due to Rifampicin-sensitive Staphylococcus spp. Rifampicine dose was categorized as follow: < 10 mg/kg/day, 10-20 mg/kg/day or > 20 mg/kg/day. The primary endpoint was patient recovery, defined as being free of infection during 12 months after the end of the initial antibiotic course.. 321 (78%) received RIF for the full antibiotic course. RIF dose didn't affect patients recovery rate with 67, 76 and 69% in the < 10, 10-20 and > 20 mg/kg/day groups, respectively (p = 0.083). In univariate analysis, recovery rate was significantly associated with gender (p = 0.012) but not to RIF dose, or Staphylococcus phenotype (aureus or coagulase-negative). In multivariate analysis, age (p = 0.01) and treatment duration (p <  0.01) were significantly associated with recovery rate.. These data suggest that lower doses of RIF are as efficient and safe as the recommended high-dose French regimen in the treatment of PJI.

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Dose-Response Relationship, Drug; Female; France; Humans; Male; Middle Aged; Prognosis; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome

Complicated methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs), particularly those with delayed culture clearance, are associated with high mortality. Combination therapy with daptomycin and ceftaroline (DAP+CPT) represents a novel therapeutic approach to MRSA-BSI owing to synergistic bactericidal activity. This study aimed to compare DAP+CPT with historical standard of care (SoC) for treatment of complicated MRSA-BSI. This single-centre retrospective cohort study included patients with complicated MRSA-BSI at University of Colorado Hospital. Patients receiving DAP+CPT for ≥48 h between November 2013 and March 2020 or SoC with vancomycin or DAP ± gentamicin and/or rifampicin from November 2011 to December 2013 were compared. The primary outcome was clinical failure defined as a composite of MRSA-related mortality and recurrent infection at 60 days. A total of 60 patients received DAP+CPT (n = 30) or SoC (n = 30). Median age was 56 years and median Pitt bacteremia score was 3. Common infectious sites were endovascular (63%) and musculoskeletal (40%). DAP+CPT was associated with a numerically lower incidence of clinical failure compared with SoC (20% vs. 43%; P = 0.052). Multivariable analysis controlling for immunocompromised status (OR, 6.90, 95% CI 1.08-44.15), Charlson comorbidity index (OR, 1.12, 95% CI 0.90-1.39) and source control (OR, 0.35, 95% CI 0.08-1.46) associated DAP+CPT with 77% lower odds of clinical failure (OR, 0.23, 95% CI 0.06-0.89). In patients with complicated MRSA-BSI with delayed clearance, DAP+CPT trended towards lower rates of clinical failure than SoC and was significantly associated with decreased clinical failure after adjustment for baseline differences.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Daptomycin; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rifampin; Salvage Therapy; Standard of Care; Staphylococcal Infections; Treatment Outcome; Vancomycin

The treatment of periprosthetic joint infection (PJI) is focused on the surgical or chemical removal of biofilm. Antibiotics in isolation are typically ineffective against PJI. Bacteria survive after antibiotic administration because of antibiotic tolerance, resistance, and persistence that arise in the resident bacteria of a biofilm. Small-colony variants are typically slow-growing bacterial subpopulations that arise after antibiotic exposure and are associated with persistent and chronic infections such as PJI. The role of biofilm-mediated antibiotic tolerance in the emergence of antibiotic resistance remains poorly defined experimentally.. We asked: (1) Does prior antibiotic exposure affect how Staphylococcus aureus survives within a developing biofilm when exposed to an antibiotic that penetrates biofilm, like rifampicin? (2) Does exposure to an antibiotic with poor biofilm penetration, such as vancomycin, affect how S. aureus survives within a developing biofilm? (3) Do small-colony variants emerge from antibiotic-tolerant or -resistant bacteria in a S. aureus biofilm?. We used a porous membrane as an in vitro implant model to grow luminescent S. aureus biofilms and simultaneously track microcolony expansion. We evaluated the impact of tolerance on the development of resistance by comparing rifampicin (an antibiotic that penetrates S. aureus biofilm) with vancomycin (an antibiotic that penetrates biofilm poorly). We performed viability counting after membrane dissociation to discriminate among tolerant, resistant, and persistent bacteria. Biofilm quantification and small-colony morphologies were confirmed using scanning electron microscopy. Because of experimental variability induced by the starting bacterial inoculum, relative changes were compared since absolute values may not have been statistically comparable.. Antibiotic-naïve S. aureus placed under the selective pressure of rifampicin initially survived within an emerging biofilm by using tolerance given that biofilm resident cell viability revealed 1.0 x 108 CFU, of which 7.5 x 106 CFU were attributed to the emergence of resistance and 9.3 x 107 CFU of which were attributed to the development of tolerance. Previous exposure of S. aureus to rifampicin obviated tolerance-mediate survival when rifampicin resistance was present, since the number of viable biofilm resident cells (9.5 x 109 CFU) nearly equaled the number of rifampicin-resistant bacteria (1.1 x 1010 CFU). Bacteria exposed to an antibiotic with poor biofilm penetration, like vancomycin, survive within an emerging biofilm by using tolerance as well because the biofilm resident cell viability for vancomycin-naïve (1.6 x 1010 CFU) and vancomycin-resistant (1.0 x 1010 CFU) S. aureus could not be accounted for by emergence of resistance. Adding rifampicin to vancomycin resulted in a nearly 500-fold reduction in vancomycin-tolerant bacteria from 1.5 x 1010 CFU to 3.3 x 107 CFU. Small-colony variant S. aureus emerged within the tolerant bacterial population within 24 hours of biofilm-penetrating antibiotic administration. Scanning electron microscopy before membrane dissociation confirmed the presence of small, uniform cells with biofilm-related microstructures when unexposed to rifampicin as well as large, misshapen, lysed cells with a small-colony variant morphology [29, 41, 42, 63] and a lack of biofilm-related microstructures when exposed to rifampicin. This visually confirmed the rapid emergence of small-colony variants within the sessile niche of a developing biofilm when exposed to an antibiotic that exerted selective pressure.. Tolerance explains why surgical and nonsurgical modalities that rely on antibiotics to "treat" residual microscopic biofilm may fail over time. The differential emergence of resistance based on biofilm penetration may explain why some suppressive antibiotic therapies that do not penetrate biofilm well may rely on bacterial control while limiting the emergence of resistance. However, this strategy fails to address the tolerant bacterial niche that harbors persistent bacteria with a small-colony variant morphology.. Our work establishes biofilm-mediated antibiotic tolerance as a neglected feature of bacterial communities that prevents the effective treatment of PJI.

Topics: Anti-Bacterial Agents; Biofilms; Drug Resistance, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Antimicrobial resistance is a growing concern in canine Staphylococcus pseudintermedius dermatitis. Treatment with rifampicin (RFP) is considered only in meticillin-resistant and multidrug-resistant S. pseudintermedius (MDR-MRSP).. To determine an optimal RFP dosing for MDR-MRSP treatment without induction of RFP resistance and identify causal mutations for antimicrobial resistance.. Time-kill assays were performed in a control isolate and three MDR-MRSP isolates at six clinically relevant concentrations [32 to 1,024 × MIC (the minimum inhibitory concentration)]. Whole-genome resequencing and bioinformatic analysis were performed in the resistant strains developed in this assay.. The genomic analysis identified nine antimicrobial resistance genes (ARGs) in MDR-MRSP isolates, which are responsible for resistance to seven classes of antibiotics. RFP activity against all four isolates was consistent with a time-dependent and bacteriostatic response. RFP resistance was observed in six of the 28 time-kill assays, including concentrations 64 × MIC in MDR-MRSP1 isolates at 24 h, 32 × MIC in MDR-MRSP2 at 48 h, 32 × MIC in MDR-MRSP3 at 48 h and 256 × MIC in MDR-MRSP3 at 24 h. Genome-wide mutation analyses in these RFP-resistant strains discovered the causal mutations in the coding region of the rpoB gene.. A study has shown that 6 mg/kg per os results in plasma concentrations of 600-1,000 × MIC of S. pseudintermedius. Based on our data, this dose should achieve the minimum MIC (×512) to prevent RFP resistance development; therefore, we recommend a minimum daily dose of 6 mg/kg for MDR-MRSP pyoderma treatment when limited antibiotic options are available.. Les résistances aux antibiotiques sont de plus en plus importantes pour les dermatites canines à Staphylococcus pseudintermedius. Le traitement à la rifampicine (RFP) est envisagé seulement pour les MDR-MRSP (S. pseudintermedius résistant à la méticilline et multi résistant). HYPOTHÈSES/OBJECTIFS: Déterminer une dose optimale de RFP pour le traitement des MDR-MRSP sans induire de résistance à RFP et identifier les mutations en cause pour la résistance antimicrobienne. MATÉRIELS ET METHODS: Le temps d’élimination a été réalisé pour une souche contrôle et trois MDR-MRSP à six concentrations cliniquement importantes [32 à 1,024 × MIC (minimum inhibitory concentration)]. Le séquençage de tout le génome et l’analyse bio-informatique ont été réalisés dans les souches résistantes développées dans cette étude. RÉSULTATS: Les analyses génomiques ont identifié neuf gènes de résistances antimicrobiennes (ARGs) dans les souches MDR-MRSP, qui étaient responsable de résistance à sept classes d’antibiotiques. L’activité RFP contre les quatre souches était compatible avec une réponse bactériostatique et temps-dépendante. La résistance à RFP a été observée pour six des 28 tests de temps d’élimination incluant les concentrations 64 x MIC des souches à MDR-MRSP1 à 24 h, 32x MIC des MDR-MRSP2 à 48h, 32 × MIC des MDR-MRSP3 à 48 h et 256 × MIC des MDR-MRSP3 à 24 h. Les analyses de mutation de génome dans ces souches résistantes à RFP ont découvert les mutations en cause dans la région codant pour le gène rpoB.. Une étude a montré que 6 mg/kg per os résultaient en des concentrations plasmatiques de 600-1000 x MIC de S. pseudintermedius. Basé sur nos données, cette dose pourrait atteindre la MIC minimum (x512) pour prévenir le développement de résistances à RFP ; ainsi, nous recommandons une dose journalière minimum de 6 mg/kg pour les pyodermites MDR-MRSP quand des options antibiotiques limitées sont disponibles.. INTRODUCCIÓN: la resistencia a los antimicrobianos es una preocupación creciente en la dermatitis canina por Staphylococcus pseudintermedius. El tratamiento con rifampicina (RFP) se considera solo en S. pseudintermedius resistente a meticilina y resistente a múltiples fármacos (MDR-MRSP). HIPÓTESIS/OBJETIVOS: determinar una dosis de RFP óptima para el tratamiento de MDR-MRSP sin inducción de resistencia a RFP e identificar mutaciones causales de resistencia a los antimicrobianos. MATERIALES Y MÉTODOS: Se realizaron ensayos de tiempo de eliminación en un aislado de control y tres aislados MDR-MRSP a seis concentraciones clínicamente relevantes [32 a 1,024 × MIC (la concentración inhibitoria mínima)]. La resecuenciación del genoma completo y el análisis bioinformático se realizaron en las cepas resistentes desarrolladas en este ensayo. RESULTADOS: el análisis genómico identificó nueve genes de resistencia a los antimicrobianos (ARGs) en los aislados de MDR-MRSP, que son responsables de la resistencia a siete clases de antibióticos. La actividad de RFP contra los cuatro aislamientos fue consistente con una respuesta bacteriostática dependiente del tiempo. Se observó resistencia a la RFP en seis de los 28 ensayos de eliminación temporal, incluidas concentraciones de 64 × MIC en aislados de MDR-MRSP1 a las 24 h, 32 × MIC en MDR-MRSP2 a las 48 h, 32 × MIC en MDR-MRSP3 a las 48 h y 256 × MIC en MDR-MRSP3 a las 24 h. Los análisis de mutaciones de todo el genoma en estas cepas resistentes a RFP descubrieron las mutaciones causales en la región codificante del gen rpoB. CONCLUSIONES Y RELEVANCIA CLÍNICA: un estudio ha demostrado que 6 mg/kg por vía oral dan como resultado concentraciones plasmáticas de 600-1.000 × CMI de S. pseudintermedius. Según nuestros datos, esta dosis debería alcanzar la CMI mínima (× 512) para prevenir el desarrollo de resistencia a la RFP; por lo tanto, recomendamos una dosis diaria mínima de 6 mg/kg para el tratamiento de la pioderma causada por MDR-MRSP cuando hay opciones limitadas de antibióticos disponibles.. Die Antibiotika Resistenz gewinnt zunehmend an Bedeutung bei der Staphylococcus pseudintermedius Dermatitis des Hundes. Eine Behandlung mit Rifampicin (RFP) wird nur in Betracht gezogen, wenn es sich um einen Methicillin-resistenten und multiresistenten S. pseudintermedius (MDR-MRSP) handelt.. Es war das Ziel, eine optimale Dosierung von RFP zur MDR-MRSP Behandlung ohne die Auslösung einer RFP Resistenz zu bestimmen und verursachende Mutationen der antimikrobiellen Resistenz zu identifizieren.. Es wurden bei einem Kontrollisolat und bei drei MDR-MRSP Isolaten Time-kill Assays bei sechs klinisch relevanten Konzentrationen [32 bis 1,024 x MIC (minimale Hemmstoffkonzentration)] durchgeführt. Eine Gesamtgenom Sequenzierung und eine bioinformatische Analyse wurde bei den resistenten Stämmen, die bei diesem Assay entstanden, durchgeführt.. Durch die Genom Analyse wurden neun Gene antimikrobieller Resistenz (ARGs) bei MDR-MRSP Isolaten identifiziert, die für die Resistenz gegenüber sieben Antibiotikaklassen verantwortlich waren. Die RFP Aktivität gegenüber den vier Isolaten war konsistent mit einer Zeit-abhängigen und bakteriostatischen Antwort. Eine RFP Resistenz wurde bei sechs der 28 Time-Kill Assays beobachtet, dabei handelte es sich um die Konzentrationen 64 x MIC bei MDR-MRSP1 Isolaten bei 24h, 32 x MIC bei MDR-MRSP2 bei 48h, 32 x MIC bei MDR-MRSP3 bei 48h und 256 x MIC bei MDR-MRSP3 bei 24h. Eine Genom-weite Mutationsanalyse bei diesen RFP-resistenten Stämmen enthüllte die verursachenden Mutationen in der Kodierungsregion des rpoB Gens.. Eine Studie hat gezeigt, dass 6 mg/kg per os in einer Plasmakonzentration von 600-1.000 x MIC von S. pseudintermedius resultiert. Basierend auf unseren Daten, sollte diese Dosis eine minimale MIC (x512) erreichen, um die Entstehung einer RFP Resistenz zu verhindern; daher empfehlen wir eine minimale tägliche Dosis von 6 mg/kg für die Behandlung einer MDR-MRSP Pyodermie, wenn nur limitierte antibiotische Optionen zur Verfügung stehen.. 背景: 犬のStaphylococcus pseudintermedius由来膿皮症では，抗菌薬耐性が問題となっている。メチシリン耐性および多剤耐性S. pseudintermedius（MDR-MRSP）に対してのみリファンピシン（RFP）による治療が検討されている。 仮説・目的: 本研究の目的は、MDR-MRSP治療においてRFP耐性を誘発しない最適なRFP投与量を決定し，抗菌薬耐性の原因となる変異を特定することであった。 材料と方法: 対照分離株1株およびMDR-MRSP分離株3株を対象に，臨床的に適切な6濃度（32～1,024×MIC（最小発育阻止濃度））でTime-kill assay法を実施した。また，Time-kill assay法で得られた耐性株を対象に，全ゲノム再配列決定およびバイオインフォマティクス解析を実施した。 結果: ゲノム解析の結果，MDR-MRSP分離株には9つの抗菌剤耐性遺伝子（ARG）が同定され，これらは7クラスの抗菌剤に対する耐性を担っていた。4株すべてに対するRFP活性は，時間依存的な静菌反応と一致していた。RFP耐性は28種のTime-kill assayのうち6種で認められ，MDR-MRSP1株では24時間後に64×MIC，MDR-MRSP2株では48時間後に32×MIC，MDR-MRSP3株では48時間後に32×MIC，MDR-MRSP3株では24時間後に256×MICの濃度であった。 結論と臨床的妥当性: 経口投与6 mg/kgで血漿中濃度がS. pseudintermediusの600～1,000×MICになるという研究結果がある。我々のデータに基づけば，この用量はRFP耐性発現を防ぐ最小MIC（512×MIC）を達成するはずである。したがって，限られた抗生物質の選択肢しかない場合のMDR-MRSP膿皮症に対する治療には，1日あたりの最小用量である6 mg/kgを推奨する。.. 背景: 抗生素耐药性是犬假中间型葡萄球菌皮炎中越来越受到关注的问题。利福平(RFP)治疗仅考虑用于耐甲氧西林和多重耐药的假中间型葡萄球菌(MDR-MRSP)。 假设/目的: 在不会诱导RFP耐药的前提下，确定MDR-MRSP治疗的最佳RFP剂量，并确定抗菌药物耐药的突变原因。 材料和方法: 在6个临床相关浓度[32-1,024×MIC（最小抑菌浓度）]下，针对对照分离株和3株MDR-MRSP分离株进行时间-杀灭试验。对本试验开发的耐药菌株进行全基因组重测序和生物信息学分析。 结果: 基因组分析在MDR-MRSP分离株中鉴定出9个抗菌药物耐药基因(ARGs)，它们是对7类抗生素耐药的原因。全部4株分离株的RFP活性与时间依赖性和抑菌反应一致。28次时间-杀菌试验中有6次观察到RFP耐药，包括在24h时MDR-MRSP1分离株的浓度为64×MIC，在48h时MDR-MRSP2的浓度为32×MIC，48h时MDR-MRSP3为32×MIC，24h时MDR-MRSP3为256×MIC。对这些RFP耐药菌株进行全基因组突变分析，发现了rpoB基因编码区是突变原因。 结论和临床相关性: 一项研究表明，6 mg/kg经口给药导致假中间型链球菌的血浆浓度为600-1,000×MIC。基于我们的数据，该剂量应达到最小MIC(×512)，以防止发生RFP耐药；因此，当可用的抗生素选择有限时，我们建议MDR-MRSP脓皮病治疗的最小日剂量为6 mg/kg。.. A resistência a antimicrobianos é uma preocupação crescente na dermatite canina causada por Staphylococcus pseudintermedius. O tratamento com rifampicina (RFP) é apenas considerado em casos de S. pseudintermedius multirresistente e resistente à meticilina (MDR-MRSP). HIPÓTESE/OBJETIVOS: Determinar a dose ideal de RFP para o tratamento de MDR-MRSP sem indução de resistência à RFP e identificar as mutações causadoras de resistência a antimicrobianos. MATERIAIS E MÉTODOS: Os ensaios de tempo de eliminação (time-kill) foram realizados em um isolado controle e três isolados MDR-MRSP em seis concentrações clinicamente relevantes [32 a 1.024 × MIC (a concentração inibitória mínima)]. O resequenciamento de todo o genoma (whole-genome resequencing) e a análise de bioinformática foram realizados nas cepas resistentes desenvolvidas neste ensaio.. A análise genômica identificou nove genes de resistência antimicrobiana (ARGs) em isolados MDR-MRSP, que são responsáveis pela resistência a sete classes de antibióticos. A atividade de RFP contra todos os quatro isolados foi consistente com uma resposta bacteriostática tempo-dependente. A resistência a RFP foi observada em seis dos 28 ensaios time-kill, incluindo concentrações 64×MIC em isolados MDR-MRSP1 em 24 h, 32×MIC em MDR-MRSP2 em 48 h, 32× MIC em MDR-MRSP3 em 48 h e 256×MIC em MDR-MRSP3 em 24 h. As análises de mutação em todo o genoma (whole genome) nessas cepas resistentes a RFP descobriram as mutações causais na região codificadora do gene rpoB. CONCLUSÕES E RELEVÂNCIA CLÍNICA: Um estudo mostrou que 6 mg/kg por via oral resulta em concentrações plasmáticas de 600-1.000 × MIC de S. pseudintermedius. Com base em nossos dados, esta dose deve atingir o MIC mínimo (×512) para evitar o desenvolvimento de resistência a RFP; portanto, recomendamos uma dose diária mínima de 6 mg/kg para o tratamento de piodermite MDR-MRSP quando há opções limitadas de antibióticos disponíveis.

Topics: Animals; Anti-Bacterial Agents; Dog Diseases; Dogs; Genomics; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus

Prosthetic joint infections (PJI) are one of the most serious complication of arthroplasty. The management of PJI needs a multidisciplinary collaboration between orthopaedic surgeon, infectious disease specialist and microbiologist. In France, the management of PJI is organized around reference centres (CRIOACs). Our main objective was to perform an audit through a questionnaire survey based on clinical cases, to evaluate how French physicians manage PJI. Eligible participants were all physicians involved in care of patients presenting a PJI. Physicians could answer individually, or collectively during a multidisciplinary team meeting dedicated to PJI. The survey consisted as three questionnaires organized in a total of six clinical cases.. Answers from the CRIOACs to the three questionnaires were 92, 77, and 53%. Between 32 and 39% of respondents did not administer antibiotic prophylaxis despite positive S. aureus pre-operative documentation. One-stage exchange strategy was widely preferred in all clinical cases, with no difference between CRIOACs and other centres. Rifampicin was prescribed for S. aureus PJI, in a situation with (90-92%) or without any prosthesis (70%). There was no consensus for the total antibiotic regimen duration, with prescriptions from six to 12 weeks for a majority of respondents.. Surgical strategy for the management of PJI was homogenous with a preference for a one-stage exchange strategy. Medical management was more heterogenous, which reflects the heterogeneity of those infections and difficulties to perform studies with strong conclusions.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Arthritis, Infectious; France; Hospitals; Humans; Physicians; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surveys and Questionnaires

Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic.. Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment.. A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 - 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 - 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 - 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome.. Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.

Topics: Anti-Bacterial Agents; Debridement; Humans; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome

Tetracyclines are widely used as oral therapy of MRSA infection, however, the pharmacodynamic underpinning is absent.. We employed an in vitro pharmacokinetic model to study the pharmacodynamics of minocycline alone and in combination with rifampicin.. An exposure-ranging design was used to establish fAUC/MIC targets for static, -1 log drop and -2 log drop effects against Staphylococcus aureus for minocycline and in combination with rifampicin. We then simulated 7-10 day human dosing of minocycline and the combination.. The minocycline fAUC/MIC for 24 h static effect and -1 log drop in bacterial load were 12.5 ± 7.1 and 23.3 ± 12.4. fAUC/MIC targets for static and -1 log drop were greater at 48 and 72 h. The addition of simulated free rifampicin associated with dosing 300 mg q12h reduced the 24 h minocycline fAUC/MICs. Simulations performed over 7-10 days exposure indicated that for minocycline standard human doses there was a 1-3 log reduction in viable count and no changes in population profiles. Addition of rifampicin resulted in larger reductions in staphylococcal load but emergence of resistance to rifampicin. There was no resistance to minocycline.. An fAUC/MIC minocycline target of 12-36 is appropriate for S. aureus. Addition of rifampicin decreases bacterial load but results in emergence of resistance to rifampicin. Unusually, there was no emergence of resistance to minocycline.

Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To identify risk factors that may predispose patients to rifampin- and cefazolin-induced coagulopathy.. An 86-year-old man with a history of rheumatoid arthritis on chronic prednisone and stage 3 chronic kidney disease, notably not on warfarin, presented to the hospital with a 10-day history of right hip pain, swelling, and drainage after a recent right total-hip arthroplasty. The patient underwent a combination of surgical intervention and medication therapy with rifampin and ceftriaxone. After discharge and at postoperative day 9, ceftriaxone was changed to cefazolin due to increasing alkaline phosphatase levels. Four weeks after the initial debridement, antibiotics, and implant retention, the patient underwent a second irrigation and debridement due to persistent infection. Cefazolin and rifampin therapy was extended. Three days later, the patient presented to the emergency room with significant bleeding at the surgical site and a profoundly elevated prothrombin time and international normalized ratio (INR). No potential contributors were identified. The Naranjo adverse drug reaction probability scale identified cefazolin and rifampin as the probable cause of elevated INR. The Liverpool adverse drug reaction avoidability assessment tool classified this adverse event as "definitely avoidable.". Rifampin-containing regimens are often recommended to treat staphylococcal prosthetic joint infections when the implant is retained. In methicillin-susceptible staphylococcal infections, cefazolin is routinely employed as the β-lactam backbone of definitive antimicrobial regimens. Although rifampin- and cefazolin-induced hypoprothrombinemia seems to be rare, adverse consequences of its occurrence may be prevented with appropriate monitoring.

Topics: Aged, 80 and over; Cefazolin; Humans; Persistent Infection; Rifampin; Staphylococcal Infections; Staphylococcus

Rifampicin is currently used to treat various bacterial infections, with the most significant application in the treatment of tuberculosis. Dose-independent side effects of the drug can lead to the development of various coagulation disorders, among which disseminated intravascular coagulation is the most dangerous. The mechanism of coagulopathy itself is multifactorial, but it is thought to be mediated by an immune response (formation of antigen-antibody complexes) and consequent damage to platelets and the vascular endothelium.. A 66-year-old woman, with numerous comorbidities including chronic renal failure, condition after implantation of a permanent pacemaker, and a positive blood culture for Staphylococcus aureus, presented with spontaneous bleeding in the muscle wall, and in the clinical picture of hemorrhagic shock.. Knowing the multifactorial mechanism of rifampicin-induced coagulopathy, possible factors were considered, such as infections, comorbidities, drug use and drug-drug interactions, pathological laboratory parameters, and coagulograms. Clinical presentation of abdominal pain and intra-abdominal mass, with laboratory verification of prolonged activated partial thromboplastin time and computed tomography-proven hematoma suspected of acute bleeding, redirects clinical suspicion of drug-induced coagulopathy.. By discontinuing rifapicin and administering vitamin K and fresh frozen plasma, normalization of laboratory coagulation parameters was achieved. Bleeding from the muscle wall required correction of acute anemia with red cell concentrates, surgical intervention, and additional antibiotic therapy for secondary infection of the operative wound.. At the end of 6 weeks of antibiotic (antistaphylococcal) therapy (due to the basic suspicion of possible infectious endocarditis), the normalization of inflammatory parameters occurred with a sterile control blood culture and a normal coagulogram.. Clinicians should be aware of the possible side effects of the administered drugs, especially taking into account the overall clinical picture of a patient, including comorbidities and possible drug interactions.

Topics: Abdominal Wall; Aged; Anti-Bacterial Agents; Disseminated Intravascular Coagulation; Female; Humans; Plasma; Rifampin; Staphylococcal Infections; Vitamin K

In this study, isolates collected in the Microbiology Laboratory of Dr. Seotomo Surabaya Hospital during May-September 2019. Then, the dilution method was carried out to determine the minimum inhibition concentration for resistant-rifampicin and dilution to determine the inhibition zone diameter. After that, DNA extraction was carried out from rifampicin-susceptible isolates as a control and resistant-rifampicin isolates followed by identification of. There were nine isolates studied. They were four resistant-rifampicin isolates and four susceptible-rifampicin isolates. In four rifampicin-resistant isolates, the most frequent mutations that occurred was His-481 codon (75%) followed by the Ile-527 codon (25%). Rifampicin-susceptible isolates mutated in Pro-475 and Asn-474 codons. One rifampicin-resistant isolate had two mutations in codons Ile-527 and Asn-474.. The type of mutation that causes the most rifampicin resistance was a missense mutation. The susceptible-rifampicin isolate experienced silent mutations. There was a relation between the type of missense mutation of

Topics: Bacterial Proteins; Codon; Drug Resistance, Bacterial; Genetic Profile; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus

After staphylococci, streptococci and enterococci are the most frequent causes of periprosthetic joint infection (PJI). MICs and minimum biofilm bactericidal concentrations of rifampin, rifabutin, and rifapentine were determined for 67 enterococcal and 59 streptococcal PJI isolates. Eighty-eight isolates had rifampin MICs of ≤1 μg/ml, among which rifabutin and rifapentine MICs were ≤ 8 and ≤4 μg/ml, respectively. There was low rifamycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Biofilms; Enterococcus; Humans; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifabutin; Rifampin; Staphylococcal Infections; Staphylococcus

Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population.. To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing.. A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2.. A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients' fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased by 50% to 60%.. This study showed that free-fat mass was a better size predictor than total body weight for ciprofloxacin clearance and volumes terms. Moreover, both MDRD and rifampicin status were significant predictors of individual ciprofloxacin clearance. Our study suggests that individual adjustment of ciprofloxacin dose in osteoarticular infections with less-susceptible bacteria might be indicated to reach required efficacy targets.

Topics: Adult; Anti-Bacterial Agents; Ciprofloxacin; Humans; Retrospective Studies; Rifampin; Staphylococcal Infections

The increasing emergence of antibiotic-resistant bacterial pathogens calls for additional urgency in the development of new antibacterial candidates. N-Phenyl-2-aminothiazoles are promising candidates that possess potent anti-MRSA activity and could potentially replenish the MRSA antibiotic pipeline. The initial screen of a series of compounds in this novel class against several bacterial strains revealed that the aminoguanidine analogues possessed promising activities and superior safety profiles. The determined MICs of these compounds were comparable to, if not better than, those of the control drugs (linezolid and vancomycin). Remarkably, compounds 3a, 3b, and 3e possessed potent activities against multidrug resistant staphylococcal isolates and several clinically important pathogens, such as vancomycin-resistant enterococci (VRE) and Streptococcus pneumoniae. In addition, the compounds were superior to vancomycin in the rapid killing of MRSA and the longer post-antibiotic effects. Furthermore, low concentrations of compounds 3a, 3b, and 3e reduced the intracellular burden of MRSA by greater than 90%. Initial in vitro PK/toxicity assessments revealed that compound 3e was highly tolerable and possessed a low metabolic clearance rate and a highly acceptable half-life.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Microsomes, Liver; Molecular Structure; Staphylococcal Infections; Structure-Activity Relationship; Thiazoles

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Genes, Bacterial; Humans; Linezolid; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phylogeny; Rifampin; Staphylococcal Infections; Tetracycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

In hernia surgery, soaking of meshes in antibiotics before implantation is a prophylactic strategy for minimizing the risk of infection while providing minimal, local, drug doses. This study describes the development and application of an antibacterial mesh coating comprising a carboxymethylcellulose gel loaded with rifampicin in a preclinical model of Staphylococcus aureus and S. epidermidis infection in rabbits.. In vitro, rifampicin-carboxymethylcellulose gel demonstrated great activity against Staphylococcus aureus/S. epidermidis, while being innocuous for fibroblasts. In vivo, rifampicin-carboxymethylcellulose gel-coated implants displayed full bacterial clearance and optimal tissue integration, irrespective of the strain of Staphylococcus. In contrast, uncoated and carboxymethylcellulose gel-coated implants exhibited macro/microscopic signs of infection and impaired tissue integration. Macrophage responses were less in rifampicin-carboxymethylcellulose gel implants than in uncoated mesh (Staphylococcus aureus/S. epidermidis; P < .01) and carboxymethylcellulose gel (S. epidermidis; P < .05) implants. Bloodstream levels of rifampicin were undetectable.. Soaking meshes in rifampicin-carboxymethylcellulose gel inhibited effectively the bacterial adhesion to the mesh without compromising the tissue repair. This antibiotic gel constitutes an easy-to-use and effective prophylactic strategy that potentially reduce the prevalence of postoperative mesh infection.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Carboxymethylcellulose Sodium; Disease Models, Animal; Hernia, Abdominal; Herniorrhaphy; Humans; Male; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Mesh; Surgical Wound Infection

Methicillin-resistant Staphylococcus aureus (MRSA) infections in cystic fibrosis (CF) patients have greatly increased in prevalence in the past two decades and may lead to a more rapid rate of lung function decline. The objective of this study was to determine the impact of a MRSA eradication protocol on long-term culture results and clinical outcomes of pediatric CF patients in a real-world setting.. This was a single-center, retrospective study of children age 30 days to 17 years. Eradication followed the STAR-too study protocol. The primary outcome was the percent of patients with MRSA-negative cultures at 12 months. Secondary outcomes were the percent of patients with negative cultures at 3, 6, and greater than 12 months and changes in clinical outcomes compared to individual baseline.. Of the 55 patients who met inclusion criteria, 10 received protocol eradication. Baseline characteristics were similar between eradication and control groups except more eradication patients were on ivacaftor (30% vs 4%; P = .037). Two eradication patients did not receive rifampin due to ivacaftor use. Eradication did not significantly increase the percent of MRSA-negative cultures at 3 months (P = .122), 6 months (P = .058), or 12 months (P = .108); however, did increase culture negativity at greater than 12 months (P = .008). Eradication resulted in no significant differences in clinical outcomes compared to control.. An extensive eradication protocol may lead to an increased clearance rate of long-term CF respiratory cultures but does not appear to affect clinical outcomes. Eradication may be reasonable to attempt; however, more data is needed before routine recommendation in all patients.

Topics: Adolescent; Aminophenols; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Quinolones; Retrospective Studies; Rifampin; Staphylococcal Infections

Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored

Topics: Anti-Bacterial Agents; Daptomycin; DNA-Directed RNA Polymerases; Drug Resistance, Microbial; Drug Therapy, Combination; Evolution, Molecular; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mutation; Polymorphism, Single Nucleotide; Rifampin; Staphylococcal Infections; Vancomycin

For management of osteoarticular infections, rifampicin appears to be the key antibiotic. We aimed to evaluate the actual rifampicin dosing regimens using a population pharmacokinetic model of rifampicin in patients with osteoarticular infections. A Monte Carlo simulation study was performed to simulate steady-state plasma concentrations for 1000 randomly sampled subjects using a total daily dose between 600 and 1200 mg (600 and 900 mg once daily, 450 and 600 mg twice daily, or 300 mg 3 times daily). When rifampicin was administered with fusidic acid, the pharmacokinetic/pharmacodynamic (PK/PD) target (area under the curve/minimum inhibitory concentration ≥952) was achieved with all tested dosing regimen, except 600 mg once daily for Staphylococcus epidermidis infections. Without coadministration of fusidic acid, none of tested dosing regimens achieved this PK/PD target. Most recommended drug-dosing regimens allow attaining the fixed area under the curve/minimum inhibitory concentration target for Staphylococcus aureus and coagulase-negative staphylococcal osteoarticular infections. In future studies, PK/PD target for osteoarticular infections in human should also be confirmed.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Rifampin; Staphylococcal Infections

To investigate whether Staphylococcus aureus bloodstream infection (SAB) patients at high risk for complications or relapse benefit from combination therapy with adjunctive rifampicin or fosfomycin.. In this post hoc analysis, SAB patients with native valve infective endocarditis, osteoarticular infections or implanted foreign devices were included. The co-primary endpoints were all-cause 90 day mortality and death or SAB-related late complications within 180 days. To overcome treatment selection bias and account for its time dependence, inverse probability of treatment weights were calculated and included in marginal structural Cox proportional hazard models (MSCMs).. A total of 578 patients were included in the analysis, of which 313 (54%) received combination therapy with either rifampicin (n = 242) or fosfomycin (n = 58). In the multivariable MSCM, combination therapy was associated with a better outcome, that is, a lower rate of death or SAB-related late complications within 180 days (HR 0.65, 95% CI 0.46-0.92). This beneficial effect was primarily seen in patients with implanted foreign devices, in which combination therapy was associated with a lower rate of death or SAB-related late complications within 180 days (HR 0.53, 95% CI 0.35-0.79) and a lower 90 day mortality (HR 0.57, 95% CI 0.36-0.91). Upon agent-specific stratification, we found no significant differences in outcomes between combination therapy containing rifampicin and fosfomycin; however, the number of patients in most subgroups was not large enough to draw firm conclusions.. In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome. Larger prospective studies are needed to validate these findings.

Topics: Anti-Bacterial Agents; Bacteremia; Fosfomycin; Humans; Prospective Studies; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Central to the regulation of bacterial gene expression is the multisubunit enzyme RNA polymerase (RNAP), which is responsible for catalyzing transcription. As all adaptive processes are underpinned by changes in gene expression, the RNAP can be considered the major mediator of any adaptive response in the bacterial cell. In bacterial pathogens, theoretically, single nucleotide polymorphisms (SNPs) in genes that encode subunits of the RNAP and associated factors could mediate adaptation and confer a selective advantage to cope with biotic and abiotic stresses. We investigated this possibility by undertaking a systematic survey of SNPs in genes encoding the RNAP and associated factors in a collection of 1,429 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. We present evidence for the existence of several, hitherto unreported, nonsynonymous SNPs in genes encoding the RNAP and associated factors of MRSA ST22 clinical isolates and propose that the acquisition of amino acid substitutions in the RNAP could represent an adaptive strategy that contributes to the pathogenic success of MRSA.

Topics: Adaptation, Physiological; Amino Acid Substitution; Anti-Bacterial Agents; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Polymorphism, Single Nucleotide; Rifampin; Staphylococcal Infections

Copolymers synthesized from acrylic acid and methacrylic acid used as gastroprotective and mucoadhesive enteric coatings have been used to prepare micro- (∼2 μm), submicro- (∼200 nm), and nanoparticles (∼20 nm) containing rifampicin (Rif) to obtain time-controlled drug release kinetics. Different particle sizes and drug release kinetics have been obtained using different synthesis conditions and fabrication techniques including the use of an electrosprayer and an interdigital microfabricated micromixer. The antimicrobial action of the encapsulated Rif has been demonstrated against

Topics: Administration, Oral; Anti-Bacterial Agents; Caco-2 Cells; Cell Line, Tumor; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Excipients; Humans; Hydrogen-Ion Concentration; Kinetics; Methacrylates; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Polymers; Polymethacrylic Acids; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Osteomyelitis carries a high risk of recurrence even after extended, aggressive antibiotic therapy. One of the key challenges is to eradicate the reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) inside the host bone cells and their biofilms. Our goal is to develop rifampicin loaded lipid-polymer hybrid nanocarriers (Rf-LPN) and evaluate if they can achieve enhanced rifampicin delivery to eradicate these intracellular and biofilm-residing MRSA. After optimization of the composition, Rf-LPN demonstrated size around 110 nm in diameter that remained stable in serum-supplemented medium, drug payload up to 11.7% and sustained rifampicin release for 2 weeks. When comparing Rf-LPN with free rifampicin, moderate but significant (p < 0.05) improvement of the activities against three osteomyelitis-causing bacteria (USA300-0114, CDC-587, RP-62A) in planktonic form were observed. In comparison, the enhancements in the activities against the biofilms and intracellular MRSA by Rf-LPN were even more substantial. The MBEC50 values against USA300-0114, CDC-587, and RP-62A were 42 vs 155, 70 vs 388, and 265 ng/ml vs over 400 ng/ml, respectively, and up to 18.5-fold reduction in the intracellular MRSA counts in osteoblasts was obtained. Confocal microscope images confirmed extensive accumulation of Rf-LPN inside the biofilm matrix and MRSA-infected osteoblasts. Overall, in this proof-of-concept study we have developed and validated the strategy to exploit the nanoparticle-cell and nanoparticle-biofilm interactions with a new rifampicin nanoformulation for prevention of osteomyelitis recurrence and chronicity caused by the elusive MRSA.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nanoparticles; Rifampin; Staphylococcal Infections

Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis.. Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively.. Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group.. Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Therapy, Combination; Foreign Bodies; Male; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Rats; Rats, Wistar; Rifabutin; Rifampin; Staphylococcal Infections; Vancomycin

Rifampicin resistance is a major therapeutic challenge, particularly in tuberculosis, leprosy, P. aeruginosa and S. aureus infections, where it develops via missense mutations in gene rpoB. Previously we have highlighted that these mutations reduce protein affinities within the RNA polymerase complex, subsequently reducing nucleic acid affinity. Here, we have used these insights to develop a computational rifampicin resistance predictor capable of identifying resistant mutations even outside the well-defined rifampicin resistance determining region (RRDR), using clinical M. tuberculosis sequencing information. Our tool successfully identified up to 90.9% of M. tuberculosis rpoB variants correctly, with sensitivity of 92.2%, specificity of 83.6% and MCC of 0.69, outperforming the current gold-standard GeneXpert-MTB/RIF. We show our model can be translated to other clinically relevant organisms: M. leprae, P. aeruginosa and S. aureus, despite weak sequence identity. Our method was implemented as an interactive tool, SUSPECT-RIF (StrUctural Susceptibility PrEdiCTion for RIFampicin), freely available at https://biosig.unimelb.edu.au/suspect_rif/ .

Topics: Antitubercular Agents; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Leprosy; Machine Learning; Mutation, Missense; Mycobacterium leprae; Mycobacterium tuberculosis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Blood Culture; Daptomycin; Epidural Abscess; Female; Humans; Linezolid; Lumbar Vertebrae; Magnetic Resonance Imaging; Methicillin-Resistant Staphylococcus aureus; Rifampin; Sacrum; Staphylococcal Infections; Temporomandibular Joint; Tomography, X-Ray Computed

Adjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors.. A post-hoc exploratory analysis using competing risks models was conducted to identify sub-groups which might benefit from rifampicin. A points-based recurrence risk score was developed and used to compare rifampicin's benefits.. Recurrence was strongly associated with liver and renal failure, diabetes and immune-suppressive drugs (p < 0.005); in contrast, failure and S. aureus-attributed mortality were associated with older age and higher neutrophil counts. Higher SOFA scores predicted mortality; higher Charlson scores and deep-seated initial infection focus predicted failure. Unexpectedly, recurrence risk increased with increasing BMI in placebo (p = 0.04) but not rifampicin (p = 0.60) participants (p. Rifampicin reduces recurrences overall; those with greatest absolute risk reductions were identified using a simple risk score. Source control and adequate duration of antibiotic therapy remain essential to prevent recurrence and improve outcomes.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Middle Aged; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.

Topics: Animals; Antibiotics, Antitubercular; Cytochrome P-450 CYP3A; Drug Interactions; Humans; Linezolid; Liver; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

We aimed to determine the evolutionary pathways of rifampicin resistance in Staphylococcus aureus, and the impact of resistance mutations in the rpoB gene on fitness.. Three clinical strains and one reference strain were used to select for rifampicin-resistant S. aureus variants. The mutations responsible for rifampicin resistance in all of the selected isolates in vitro were investigated by polymerase chain reaction (PCR) and DNA sequencing. To compare the fitness cost of rpoB mutations against their corresponding original isolates, we performed bacterial growth curve assays, static biofilm assays, in vitro competition experiments and an infection model of Galleria mellonella larvae.. We obtained four rifampicin-resistant S. aureus isolates that showed high levels of resistance to rifampicin with a minimal inhibitory concentration (MIC) of 128 mg/L, and all isolates had a mutation at position 481 (H481F/Y) in RpoB. A broth microdilution assay indicated that mutation of H481F/Y did not affect susceptibility to common antibacterial drugs but slightly increased the vancomycin MIC. To identify the pathways involved in the development of rifampicin resistance, 32 variants (eight mutants for each strain) and four original isolates were selected for gene sequencing. Different generations of isolates were found to harbor various mutations sites. Compared with the corresponding original isolates, an in vitro fitness assay of the variant isolates showed that growth and virulence were reduced, with a statistically significantly decreased fitness, whereas the capacity for biofilm formation was elevated.. Our findings suggested that the acquisition of rifampicin resistance in S. aureus was dynamic and was associated with a significant fitness cost.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Biological Evolution; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Genetic Fitness; Humans; Microbial Sensitivity Tests; Moths; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Virulence

Topics: Aneurysm, Infected; Anti-Bacterial Agents; Bacteremia; Clindamycin; Conservative Treatment; Drug Combinations; Drug Therapy, Combination; Echocardiography; Female; Heart Septal Defects, Ventricular; Humans; Infant; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pulmonary Artery; Radiography; Rifampin; Staphylococcal Infections; Sulfamethizole; Trimethoprim

Staphylococcus aureus causes a variety of symptoms and diseases and has been associated with high morbidity and mortality. A global population drift in clinical S. aureus isolates towards reduced antimicrobial susceptibility is being reported. In this study, the antimicrobial susceptibility profile and minimum inhibitory concentration (MIC) creep of vancomycin, linezolid, teicoplanin and rifampicin against clinical S. aureus isolates at an Indian tertiary centre from January 2012 to December 2016 were investigated.. All consecutive, non-duplicate S. aureus isolates (n=1466) recovered from hospitalised patients identified by VITEK. S. aureus isolates recovered from all clinical samples demonstrated high resistance to ampicillin, ciprofloxacin and penicillin (75-100%) and low resistance to amikacin, linezolid, netilmicin, nitrofurantoin, teicoplanin and vancomycin (0-13%). The MIC. Despite remaining susceptible, S. aureus is not inert to antibiotic pressure. Implementation of preventive measures in healthcare settings is required worldwide to combat the increasing number of infections by this pathogen.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Hospitalization; Humans; India; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Tertiary Care Centers; Vancomycin

Topics: Animals; Anti-Bacterial Agents; Cornea; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Humans; Keratitis; Mice; Mice, Inbred BALB C; Moxifloxacin; Ophthalmic Solutions; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Trimethoprim

Bone infection is a devastating condition resulting from implant or orthopaedic surgery. Therapeutic strategies are extremely complicated and may result in serious side effects or disabilities. The development of enhanced 3D scaffolds, able to promote efficient bone regeneration, combined with targeted antibiotic release to prevent bacterial colonization, is a promising tool for the successful repair of bone defects. Herein, polymeric electrospun scaffolds composed of polycaprolactone (PCL) nanofibres decorated with poly(lactic-co-glycolic acid) (PLGA) particles loaded with rifampicin were fabricated to achieve local and sustained drug release for more efficient prevention and treatment of infection. The release profile showed an initial burst of rifampicin in the first six hours, enabling complete elimination of bacteria. Sustained and long-term release was observed until the end of the experiments (28 days), facilitating a prolonged effect on the inhibition of bacterial growth, which is in agreement with the common knowledge concerning the acidic degradation of the microparticles. In addition, bactericidal effects against gram negative (Escherichia coli) and gram positive (Staphylococcus aureus) bacteria were demonstrated at concentrations of released rifampicin up to 58 ppm after 24 h, with greater efficacy against S. aureus (13 ppm vs 58 ppm for E. coli). Cell morphology and cytocompatibility studies highlighted the suitability of the fabricated scaffolds to support cell growth, as well as their promising clinical application for bone regeneration combined with prevention or treatment of bacterial infection.

Topics: Anti-Bacterial Agents; Bone Regeneration; Cell Proliferation; Cells, Cultured; Drug Delivery Systems; Escherichia coli; Escherichia coli Infections; Humans; Hydrodynamics; Nanofibers; Osteoblasts; Polylactic Acid-Polyglycolic Acid Copolymer; Rifampin; Staphylococcal Infections; Staphylococcus aureus

In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating.. A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens.. In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 10 ± 2.1 × 10 CFUs; p < 0.001), bone (6.9 × 10 ± 3.1 × 10 CFUs; p < 0.05), and implant (5.1 × 10 ± 2.2 × 10 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source.. By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating.. The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.

Topics: Analysis of Variance; Animals; Anti-Bacterial Agents; Delayed-Action Preparations; Disease Models, Animal; Drug Combinations; Linezolid; Luminescent Measurements; Male; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

The aim of this study was to investigate the antibacterial activity of a synthetic aryl isonitrile compound (35) that was developed as part of a compound library to identify new antibacterial agents effective against methicillin-resistant Staphylococcus aureus (MRSA).. Compound 35 was evaluated against MRSA isolates by the broth microdilution assay and for toxicity to mammalian keratinocytes using the MTS assay. A multistep resistance selection assay was conducted to investigate MRSA resistance development to 35. A Caco-2 bidirectional permeability assay was employed to evaluate the ability of 35 to permeate across the gastrointestinal tract, and compound 35 was incubated with human liver microsomes to determine susceptibility to hepatic metabolism. Finally, compound 35 was evaluated in an uncomplicated MRSA skin infection mouse model and an MRSA neutropenic thigh infection mouse model.. Compound 35 inhibited the growth of MRSA clinical isolates at 2-4μM and was non-toxic to human keratinocytes. No resistance formation was observed with MRSA against compound 35 after 10 serial passages. In a murine skin wound model, compound 35 significantly reduced the burden of MRSA, similar to the antibiotic fusidic acid. Compound 35 exhibited a marked improvement both in permeability and stability to hepatic metabolism (half-life >11h) relative to the first-generation lead compound. In a neutropenic thigh infection mouse model, compound 35 successfully reduced the burden of MRSA in immunocompromised mice.. In summary, compound 35 was identified as a new lead aryl isonitrile compound that warrants further investigation as a novel antibacterial agent.

Topics: Animals; Anti-Bacterial Agents; Caco-2 Cells; Disease Models, Animal; Female; Fusidic Acid; Humans; Keratinocytes; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microsomes, Liver; Nitriles; Rifampin; Skin; Staphylococcal Infections; Staphylococcal Skin Infections

Between July 2011 and May 2016, a total of 40

Topics: Animals; Anti-Bacterial Agents; Chloramphenicol; Chloramphenicol Resistance; Cross Infection; Disease Outbreaks; Genotype; Horses; Hungary; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Topics: Adenosine; Animals; Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; In Vitro Techniques; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Prosthesis-Related Infections; Pseudomonas aeruginosa; Purinergic P2Y Receptor Antagonists; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus agalactiae; Ticagrelor; Vancomycin; Vancomycin-Resistant Enterococci

A 56-year-old man sought care from a primary care physician (PCP) 5 days after lifting a heavy box produced acute, isolated lumbar pain. The PCP diagnosed a lumbar disc herniation and referred the patient to physical therapy without diagnostic imaging. Due to the presence of multiple red flags leading up to and during examination, the patient was transferred to the emergency department for further evaluation. Magnetic resonance imaging revealed a spinal epidural abscess with an associated multiloculated abscess within the adjacent left paraspinal muscles.

Topics: Abscess; Anti-Bacterial Agents; Diagnosis, Differential; Humans; Low Back Pain; Male; Middle Aged; Oxacillin; Paraspinal Muscles; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The mortality rate for Staphylococcus aureus endocarditis remains as high as 20-30% despite improvements in medical and surgical treatment. This study evaluated the efficiency and tolerance of a combination of intravenous trimethoprim-sulfamethoxazole and clindamycin (T&C) +/- rifampicin and gentamicin, with a rapid switch to oral administration of T&C.. This before-after intervention study compared the outcomes of 170 control patients before introduction of the T&C protocol (2001-2011) with the outcomes of 171 patients in the T&C group (2012-2016). All patients diagnosed with S. aureus infective endocarditis and referred to the study centre between 2001 and 2016 were included. Between 2001 and 2011, the patients received a standardized antibiotic treatment: oxacillin or vancomycin for 6 weeks, plus gentamicin for 5 days. Since February 2012, the antibiotic protocol has included a high dose of T&C (intravenous, switched to oral administration on day 7). Rifampicin and gentamicin are also given in cases of cardiac abscess or persistent bacteraemia.. The two groups were slightly different. On intention-to-treat analysis, global mortality (19% vs 30%, P=0.024), in-hospital mortality (10% vs 18%, P=0.03) and 30-day mortality (7% vs 14%, P=0.05) were lower in the T&C group. The mean duration of hospital stay was significantly shorter in the T&C group (30 vs 39 days; P=0.005).. The management of S. aureus infective endocarditis using a rapid shift to oral administration of T&C reduced the length of hospital stay and the mortality rate.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Gentamicins; Humans; Male; Middle Aged; Prospective Studies; Rifampin; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection.. All regimes led to a significant decrease in CFU count compared with controls (1-2 log. Levofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.

Topics: Anti-Bacterial Agents; Cell Line; Colony Count, Microbial; Humans; Levofloxacin; Microbial Sensitivity Tests; Microbial Viability; Models, Theoretical; Osteoarthritis; Osteoblasts; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Bacterial keratitis causes significant blindness, yet antimicrobial resistance has rendered current treatments ineffective. Polymyxin B-trimethoprim (PT) plus rifampin has potent

Topics: Animals; Anti-Bacterial Agents; Cornea; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Keratitis; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim

Infections to the peritoneal catheter are common in Peritoneal Dialysis (PD). We report the clinical case of a 49-year-old male patient in PD, who showed an atypical manifestation of tunnel infection caused by Staphylococcus aureus. The infection was characterized by a little abscess, on the left pararectal abdominal line, 6 cm far from exit-site of the peritoneal catheter. The diagnosis was made using ultrasonography (US), which showed a fistulous communication from subcutaneous cuff to the skin. We treated the infection conservatively by performing cuff-shaving and drainage of the abscess, associated to antibiotic therapy (teicoplanin). Due to the persistence of the infection, we added oral and topical rifampicin, and advanced medication with freez-dried collagen plant impregnated with extended-release gentamicin. The complete resolution of the infection allowed us to avoid removing the catheter.

Topics: Abdominal Wall; Abscess; Anti-Bacterial Agents; Catheter-Related Infections; Combined Modality Therapy; Drainage; Gentamicins; Humans; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Polycystic Kidney, Autosomal Dominant; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Ultrasonography

A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Caco-2 Cells; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rats, Sprague-Dawley; Staphylococcal Infections; Thiazoles

Methicillin and vancomycin resistant Staphylococcus aureus infections are an emerging global health concern leading to increasing morbidity and mortality. Continuous increase in drug resistance has underlined the need for discovery and development of new antibacterial agents acting via novel mechanisms to overcome this pressing issue. In this context, a number of 1,2,3-triazole linked 4(3H)-quinazolinone derivatives were designed and synthesized as potent antibacterial agents. When evaluated against ESKAP pathogen panel, compounds 7a, 7b, 7c, 7e, 7f, 7g, 7h, 7i, 9a, 9c, 9d and 9e exhibited significantly selective inhibitory activities towards Staphylococcus aureus (MIC = 0.5-4 μg/mL). To understand and confirm the specificity of these compounds, the compounds 7a and 9a were tested against E. coli and A. baumannii in combination with sub-lethal concentrations of Polymyxin B nonapeptide (PMBN) and were found to be inactive. This clearly indicated that these compounds possess specific and potent activity towards S. aureus and are inactive against gram-negative pathogens. Encouragingly, the compounds were also found to be non toxic to Vero cells and displayed favourable selectivity index (SI = 40 to 80). Furthermore, 7a and 9a were found to possess potent inhibitory activity when tested against multidrug resistant S. aureus including strains resistant to vancomycin (MIC values 0.5-32 μg/mL), indicating that the compounds are able to escape current drug-resistance mechanisms. With the potent anti-bacterial activity exhibited the new series of 1,2,3-triazole linked 4(3H)-quinazolinones have emerged as promising candidates for treating multidrug resistant Staphylococcus aureus infections.

Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Quinazolinones; Staphylococcal Infections; Structure-Activity Relationship; Triazoles

The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin.. Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up.. Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains.. Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA.

Topics: Aged; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Moxifloxacin; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus.. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used.. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients.. Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not associated with increased resistance of S. aureus isolates to rifampin or tetracyclines.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Drug Resistance, Bacterial; Hospitals, Teaching; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Urban Population

The long-term impact of treatment strategies proposed by the IDSA guidelines for patients presenting with methicillin-susceptible S. aureus (MSSA) prosthetic joint infection (PJI) is not well-known.. Retrospective (2000-2010) cohort study including patients presenting with MSSA hip or knee PJI. A univariate Cox analysis was performed to determine if the non-compliance with IDSA surgical guidelines was a risk factor for treatment failure.. Eighty-nine patients with a mean follow-up of 2.8 years were included. Non-compliance with IDSA surgical guidelines was associated with treatment failure (hazard ratio 2.157; 95% CI [1.022-4.7]). The American Society of Anesthesiologists score, inadequate antimicrobial therapy, and a rifampicin-based regimen did not significantly influence patient outcome.. Based on the IDSA guidelines, if a patient presenting with MSSA PJI is not eligible for implant retention, complete implant removal is needed to limit treatment failure.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Biofilms; Combined Modality Therapy; Conservative Treatment; Debridement; Device Removal; Drug Therapy, Combination; Female; Follow-Up Studies; Guideline Adherence; Hip Prosthesis; Humans; Infusions, Intravenous; Knee Prosthesis; Male; Methicillin; Middle Aged; Practice Guidelines as Topic; Proportional Hazards Models; Prosthesis-Related Infections; Recurrence; Retrospective Studies; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

The goal of this study was to determine the effectiveness of antibiotics on Staphylococcus epidermidis biofilms with different proportions of dormant bacteria, using clinical and commensal isolates.. The ability of S. epidermidis isolates to develop a dormant state was determined. The susceptibility of biofilms with prevented or induced dormancy to antibiotics was evaluated by enumeration of viable and cultivable cells, and confocal microscopy.. Dormancy was observed in the majority of tested strains. Tetracycline and rifampicin enhanced the development of a viable but noncultivable biofilm state.. Biofilms with induced dormancy were more likely to survive rifampicin. Furthermore, we found that the reduction of cultivable cells was not sufficient to reach definite conclusions on antimicrobial effectiveness.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tetracycline

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Rifampin; Staphylococcal Infections; Staphylococcus aureus

A deep sternal wound infection (DSWI) can become a severe complication after cardiac surgery, with in-hospital mortality rates reaching up to 35%. Staphylococci, particularly methicillin resistant Staphylococcus aureus (MRSA), play important roles in its etiology.. This case report presents a patient who underwent coronary artery bypass surgery, and suffered postoperatively from a DSWI caused by MRSA. The pathogen was susceptible to vancomycin and rifampicin in vitro; however, this therapy was clinically ineffective. Both clinical improvement and MRSA eradication were achieved after surgical debridement of the wound and the intravenous administration of dalbavancin.. We decided to administer dalbavancin because of its convenient pharmacological profile. The patient's tolerance of the antimicrobial was good, the biochemical markers of inflammation returned to the normal ranges, and the microbiological results one week after the dalbavancin administration were negative. A good clinical outcome was achieved with both the surgery and antimicrobial administration. In this case, dalbavancin was more effective in the treatment of the sternal and surrounding tissue infections caused by MRSA, when compared to vancomycin.

Topics: Anti-Bacterial Agents; Coronary Artery Bypass; Debridement; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; ST Elevation Myocardial Infarction; Staphylococcal Infections; Sternum; Surgical Wound Infection; Teicoplanin; Vancomycin

In individuals with cystic fibrosis (CF), colonization with methicillin-resistant Staphylococcus aureus (MRSA) was reported to be associated with a deterioration of pulmonary disease as reflected by an accelerated decline in lung function. Thus, an early eradication of MRSA could be beneficial in these patients. Here, we report on an intensified MRSA eradication protocol.. Since 2012 a protocol for the eradication of newly acquired MRSA has been used in our CF Clinic, combining oral rifampicin and fusidic acid, inhaled vancomycin, nasal mupirocin, local antiseptic treatment and hygienic directives all of which are applied for only 7 days during an inpatient hospital stay.. Since 2012 seven patients (3 male, 4 female; age range 4 to 30 years) newly acquired MRSA. In 6 of the 7 patients (86%) successful eradication of MRSA was achieved upon first treatment using the protocol described above. In one patient a second course of treatment was performed which, however, also failed to eliminate the colonizing MRSA.. Our protocol led to an eradication rate of 86%. The impact of each individual component of the protocol remains to be determined.

Topics: Administration, Inhalation; Administration, Intranasal; Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Baths; Child; Child, Preschool; Cystic Fibrosis; Drug Therapy, Combination; Female; Fusidic Acid; Hand Disinfection; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Retrospective Studies; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin; Young Adult

Spontaneous methicillin-resistant Staphylococcus aureus (MRSA) meningitis is extremely rare and has a high mortality rate. We report a case of MRSA meningitis in an otherwise healthy young adult female with no recent trauma or neurosurgical interventions. Despite antibiotics she suffered a vasculitis-induced cerebral vascular ischemic event.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Aspirin; Cerebellum; Female; Humans; Meningitis, Bacterial; Methicillin-Resistant Staphylococcus aureus; Prednisone; Rifampin; Risk Factors; Severity of Illness Index; Staphylococcal Infections; Vancomycin; Young Adult

The CFTR potentiator ivacaftor is responsible for significant clinical improvements among a subset of patients with cystic fibrosis. Because it is a substrate of the cytochrome P450 system, specifically CYP3A4/5, ivacaftor is subject to significant drug-drug interactions, including due to commonly used antimicrobials such as rifampin. While the interaction of rifampin and ivacaftor has been examined in vitro, severe adverse events resulting from this interaction have not been reported in the literature. In this report, we describe the termination of steady, long-term improvement in a patient taking ivacaftor, resulting from the use of rifampin and precipitating a significant pulmonary exacerbation.

Topics: Adult; Aminophenols; Anti-Bacterial Agents; Chloride Channel Agonists; Cystic Fibrosis; Cytochrome P-450 CYP3A; Drug Interactions; Female; Humans; Medication Adherence; Methicillin-Resistant Staphylococcus aureus; Quinolones; Rifampin; Staphylococcal Infections; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Double-Blind Method; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE).. From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin.. Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis.. The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Topics: Aged; Anti-Bacterial Agents; Cloxacillin; Endocarditis, Bacterial; Female; Gentamicins; Heart Failure; Heart Valve Prosthesis; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Prosthesis-Related Infections; Renal Insufficiency; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Open fractures become infected despite meticulous debridement and care. Locally applied antibiotics, commonly embedded in polymethylmethacrylate, deliver high doses of drug directly to the fracture site. Direct application of antibiotic powder, which is being applied prophylactically in spine surgery, is a recent interest in the trauma sector, where bacterial biofilms are more prevalent. Traditional antibiotics, such as vancomycin, are poor performers against bacterial biofilms thus are ineffective in delayed treatment. Rifampin is an effective eradicator of Staphylococcal biofilms. Here, a rat model of musculoskeletal trauma was used to evaluate the utility of locally applied rifampin powder for reducing established orthopedic Staphylococcal infections in a delayed treatment scenario that previously indicated the limited use of local vancomycin. By applying rifampin powder directly to the contaminated segmental defect, the number of bacteria, as well as clinical indications of infection, were significantly reduced compared to vancomycin and daptomycin. Considering the Infectious Disease Society of America's recommendation to use rifampin in combination with another antibiotic to reduce the onset of rifampin resistance, rifampin powder was also applied in combination with vancomycin or daptomycin with insignificant changes in eradication performance. No indications of rifampin resistance were identified. Clinical Significance: The use of locally applied rifampin is a promising therapy for mature and tolerant musculoskeletal infections. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:3136-3141, 2018.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Biofilms; Disease Models, Animal; Musculoskeletal System; Polymethyl Methacrylate; Powders; Rats; Rats, Inbred Lew; Rifampin; Staphylococcal Infections; Time-to-Treatment; Vancomycin

The chloramphenicol/florfenicol resistance gene cfr, which mediates cross-resistance to linezolid and other classes of antimicrobial agents, represents a global therapeutic challenge due to its dissemination among MDR nosocomial pathogens, including MRSA. This study aimed to compare the efficacy of the linezolid/rifampicin combination in a murine pneumonia model caused by cfr-positive and cfr-negative clinical MRSA strains.. Synergistic activity between linezolid and rifampicin was evaluated by chequerboard and time-kill assays. Pharmacokinetic profiles in plasma and epithelial lining fluid (ELF) as well as the therapeutic efficacy of linezolid alone and in combination with rifampicin were investigated in a murine pneumonia model. The Emax Hill equation was used to model the dose-response relationship.. Increased susceptibility of the study MRSA strains to linezolid was observed with the rifampicin combination (MIC decreased 2- to 16-fold versus linezolid alone). The combination had synergistic activity (fractional inhibitory concentration index ≤0.5) against all cfr-positive MRSA isolates. Linezolid demonstrated excellent pulmonary penetration with an ELF/fplasma AUC ratio of 2.68 ± 0.17. The addition of rifampicin significantly improved the efficacy of linezolid in the pneumonia model due to cfr-positive and cfr-negative MRSA strains. The fAUC/MIC targets of linezolid associated with stasis, 1 log10 kill and 2 log10 kill were 15.9, 38.8 and 175 in plasma, and 43.5, 108 and 415 in ELF, respectively. Importantly, the linezolid fAUC/MIC targets in both plasma and ELF were 2.4-6.7 times lower in combined linezolid/rifampicin therapy versus linezolid monotherapy (P < 0.005).. Combination of linezolid with rifampicin significantly improved the efficacy of linezolid in the murine pneumonia model caused by MRSA strains in the presence and absence of the cfr gene.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Linezolid; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections

To evaluate factors associated with failure in patients treated with DAIR (debridement, antibiotic therapy, and implant retention) for Staphylococcus aureus prosthetic joint infections (PJIs). We retrospectively analyzed consecutive patients with stable PJI due to S. aureus treated with DAIR at six hospitals between 2010 and 2014. Cox proportional hazards regression was used to study factors associated with treatment failure at 2 years. Of 154 eligible patients, 137 were included (mean age 73 ± 13 years; male 56%). The estimated success rate according to the Kaplan-Meier method was 76.2 [95% CI 68-83] at 2 years of follow-up. In multivariate analysis, longer duration of treatment (hazard ratio (HR) 0.78 [0.69-0.88]; p < 0.001) and combination therapy including rifampin (HR 0.08 [0.018-0.36]; p = 0.001) were independently associated with success, whereas active smoking was independently associated with failure (HR 3.6 [1.09-11.84]; p = 0.036). When the analysis was restricted to patients with early infection onset (< 3 months), early acute infection was also predictive of a better prognosis (HR 0.25 [0.09-0.7]; p = 0.009). Failure was not associated with time from prosthesis insertion to debridement, nor with duration of symptoms > 3 weeks and type of prosthesis (hip or knee). These results remained unchanged when the 14 patients under immunosuppressive therapy were removed from analysis. These data suggest that DAIR can be performed even if infection and symptoms are delayed but reserved to patients who are able to follow rifampin-based combination therapy for a prolonged duration that should not be different for hip and knee PJI.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Debridement; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.

Topics: Anti-Bacterial Agents; Biological Coevolution; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genome, Bacterial; Mutation; Phylogeny; Prevalence; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Purulent pericarditis occurs rarely in the current antibiotic era. We describe clinical and echocardiographic features of purulent pericarditis in a previously healthy child with influenza and community-acquired methicillin-resistant Staphylococcus aureus co-infection. The child was already on appropriate antibiotics and had a very subtle clinical presentation, with prominent abdominal symptoms. Timely surgical drainage led to complete recovery.

Topics: Anti-Bacterial Agents; Child, Preschool; Community-Acquired Infections; Humans; Influenza B virus; Influenza, Human; Male; Methicillin-Resistant Staphylococcus aureus; Pericarditis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The aim of our study was to determine whether rifampin resistance emerges in human skin staphylococci after oral intake of rifaximin for surgical prophylaxis. Rifampin-resistant staphylococci appeared on the skin of 32 out of 74 patients (43.2%) two weeks after prophylactic treatment with rifaximin. In all cases, the resistant strains were coagulase-negative staphylococci. The resistance completely reverted after three months. This study shows the emergence of transient resistance to rifampin after rifaximin intake.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Colorectal Surgery; Drug Resistance, Multiple, Bacterial; Elective Surgical Procedures; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Rifampin; Rifaximin; Staphylococcal Infections; Staphylococcus

Spinal implant infection is a rare but significant complication of spinal fusion surgery, and the most common pathogen is Staphylococcus aureus. It is difficult to treat due to this pathogen's biofilm-forming ability and antibiotic resistance. We evaluated the therapeutic outcome of treatments for S aureus spinal implant infections. We retrospectively reviewed all patients with S aureus spinal implant infections at 11 tertiary-care hospitals over a 9-year period. Parameters predictive of treatment failure and recurrence were analyzed by Cox regression. Of the 102 patients with infections, 76 (75%) were caused by methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In all, 83 (81%) patients were managed by debridement, antibiotics, and implant retention (DAIR) and 19 (19%) had their implants removed. The median duration of all antibiotic therapies was 52 days. During a median follow-up period of 32 months, treatment failure occurred in 37 (36%) cases. The median time to treatment failure was 113 days, being <1 year in 30 (81%) patients. DAIR (adjusted hazard ratio [aHR], 6.27; P = .01) and MRSA infection (aHR, 4.07; P = .009) were independently associated with treatment failure. Rifampin-based combination treatments exhibited independent protective effects on recurrence (aHR, 0.23; P = .02). In conclusion, among patients with S aureus spinal implant infections, MRSA and DAIR were independent risk factors for treatment failure, and these risk factors were present in the majority of patients. In this difficult-to-treat population, the overall treatment failure rate was 36%; rifampin may improve the outcomes of patients with S aureus spinal implant infections.

Topics: Aged; Anti-Bacterial Agents; Debridement; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Risk Factors; Spinal Fusion; Staphylococcal Infections; Staphylococcus aureus; Tertiary Care Centers

The aim of the present study was to investigate potential predictive factors of an unfavorable outcome in patients with prosthetic joint infection (PJI) undergoing 2-stage exchange.. Patients with PJI undergoing 2-stage exchange and observed over a 5-year period (2009-2013) were included. Cure was defined by the disappearance of infection after a 96-week follow-up period. Statistical analysis was performed using the Mann-Whitney U test, the Fisher exact test, and the multivariate analysis.. One-hundred twenty-two patients with PJI were included (median age, 69 years [range, 36-80 years]; 48% males, 47 hip PJI, and 75 knee PJI). Known comorbidities related to an increased risk of infection were reported in 43 patients (35%). Microbiological definition was obtained in 101 (83%) patients, and Staphylococcus aureus was isolated in 44 (36%) patients. Coagulase-negative staphylococci were isolated in 41 (34%) patients. A favorable outcome was obtained in 102 of 122 patients (84%). After univariate analysis, bacterial growth from operative specimens (P = .007), growth of Gram-positive bacteria (P < .001), use of oral therapy (P = .01), and absence of known comorbidities (P = .02) were associated with favorable outcome. Administration of rifampin (P = .99) and results of blood analysis were not predictive of outcome. After multivariate analysis was applied, infection sustained by Gram-positive bacteria, administration of oral antibiotics, and absence of known comorbidities frequently resulted in favorable outcome.. A favorable outcome in patients with PJI undergoing 2-stage procedure was associated with an infection sustained by Gram-positive bacteria, absence of known comorbidities, and administration of oral therapy. Therefore, failure rate can be reduced with appropriate treatment choices.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Comorbidity; Female; Hip Prosthesis; Humans; Italy; Joint Diseases; Knee Joint; Knee Prosthesis; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prostheses and Implants; Prosthesis-Related Infections; Reoperation; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Topics: Anti-Bacterial Agents; Drug Interactions; Fusidic Acid; Humans; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses, often with suboptimal clinical outcomes including increased morbidity and health-care costs. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI.. Oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment were administered at human-exposure doses for 6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and reactive bone changes were evaluated with radiographs and micro-computed tomography (μCT) imaging.. Oral-only linezolid-rifampin and all intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria and minimized reactive bone changes. Although oral linezolid was the most effective monotherapy, all oral and intravenous antibiotic monotherapies failed to clear infection or prevent reactive bone changes.. Combination antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the newer ceftaroline-rifampin combinations, were highly effective and more efficacious than monotherapies when used against a preclinical MRSA PJI.. This study provides important preclinical evidence to better optimize future antibiotic therapy against PJIs. In particular, the oral-only linezolid-rifampin option might reduce venous access complications and health-care costs.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Daptomycin; Disease Models, Animal; Doxycycline; Drug Combinations; Linezolid; Methicillin-Resistant Staphylococcus aureus; Mice; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Bone and Bones; Drug Administration Routes; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Humans; Joints; Malaria Vaccines; Plasmids; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Rifampin; Staphylococcal Infections

Catheter-related bloodstream infections (CRBSIs) are among the most common hospital-acquired infections. We aimed to survey methicillin resistance, biofilm production and susceptibility to vancomycin, linezolid and other antibiotics for staphylococci isolated from CRBSIs.. Fifty-eight isolates [20 S. aureus and 38 coagulase-negative staphylococci (CoNS; 20 Staphylococcusepidermidis, nine Staphylococcushaemolyticus, three Staphylococcusschleiferi, two Staphylococcuswarneri and four Staphylococcuslugdunensis)] were tested for methicillin resistance by cefoxitin disk diffusion and detection of the mecA gene by PCR; biofilm-forming ability using Congo red agar and tissue culture plate methods; susceptibility to ciprofloxacin, clindamycin, cotrimoxazole, erythromycin, gentamicin, linezolid, rifampicin and tetracycline; and MIC determination for vancomycin.Results/Key findings. Cefoxitin resistance was detected among 40 % (8/20) S. aureus isolates, 70 % (14/20) S. epidermidis isolates and 16.7 % (3/18) of other CoNS, although the mecA gene was detected in 45 % (9/20) S. aureus isolates, 35 % (7/20) S. epidermidis isolates and 16.7 % (3/18) of other CoNS. Biofilm-forming ability ranged from 45 to 75 %. Methicillin-resistant S. aureus and other CoNS were considered to be more virulent than methicillin-resistant S. epidermidis due to the higher biofilm forming abilities of the former. All tested isolates exhibited 100 % sensitivity to vancomycin and linezolid, irrespective of their methicillin resistance or biofilm-forming ability. Rifampicin showed overall sensitivity of 75.9 %. Varying degrees of multi-resistance were found for the other antibiotics.. Vancomycin, linezolid and rifampicin could be used effectively against methicillin-resistant staphylococci isolated from CRBSIs.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Biofilms; Catheter-Related Infections; Catheters; Drug Resistance, Bacterial; Egypt; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Polymerase Chain Reaction; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Tertiary Care Centers; Vancomycin

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Daptomycin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Joint Prosthesis; Male; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Salvage Therapy; Staphylococcal Infections; Treatment Outcome

Staphylococcus aureus is one of the most frequent pathogens responsible for biofilm-associated infections. Among current clinical antibiotics, very few enable long-term successful treatment. Thus, it becomes necessary to better understand antibiotic failures and successes in treating infections in order to master the use of proper antibiotic therapies. In this context, we took benefit from a set of fluorescence spectroscopy and imaging methods, with the support of conventional microbiological tools to better understand the vancomycin-rifampin combination (in)efficiency against S. aureus biofilms. It was shown that both antibiotics interacted by forming a complex. This latter allowed a faster penetration of the drugs before dissociating from each other to interact with their respective biological targets. However, sufficiently high concentrations of free vancomycin should be maintained, either by increasing the vancomycin concentration or by applying repetitive doses of the two drugs, in order to eradicate rifampin-resistant mutants.

Topics: Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Optical Imaging; Rifampin; Spectrometry, Fluorescence; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Although new antimicrobial agents designed to treat infections with limited therapeutic options have been introduced in the past few years, resistant Gram positive cocci have continued to emerge and spread. Daptomycin is a cyclic lipopeptide antibiotic that has rapid bactericidal activity against broad spectrum of Gram positive bacteria, including methicillin resistant Staphylococcus aureus (MRSA). Antibiotics are sometimes used in combination in an attempt to prevent or delay the in vivo emergence of drug-resistant subpopulations of pathogenic organisms. The aim of the study was to evaluate in vitro activity of daptomycin combinations with rifampicin, gentamicin, fosfomycin, and fusidic acid against MRSA strains.. In total, 25 strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using a microbroth dilution assay. The in vitro activities of antibiotics in combination were assessed using the microbroth checkerboard technique. With this method, the fractional inhibitory concentration index was interpreted as follows: synergism ≤0.5; additive/indifference >0.5-≤4; antagonism >4.. According to the MIC values, all strains (100%) were susceptible to daptomycin, 16% (4/25) to rifampicin, 20% (5/25) to gentamicin, 44% (11/25) to fosfomycin, and 72% (18/25) to fusidic acid. Synergistic interaction of daptomycin in combinations with rifampicin, gentamicin, fosfomycin, and fusidic acid were found as 12%, 68%, 100% and 16%, respectively. No antagonism was observed.. The combination of daptomycin with fosfomycin may be a promising alternative therapy of MRSA infections.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Fusidic Acid; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

Open fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model.. PMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance.. There was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed.. Although higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Carriers; Fractures, Open; Polymethyl Methacrylate; Rats; Rats, Inbred Lew; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Wound Infection

Indiscriminate use of antibiotics globally has lead to an increase in emergence of drug-resistant pathogens under both nosocomial, as well as more worryingly, in community setting as well. Further, a decrease in the corporate interest and financial commitment has exerted increasing pressure on a rapidly dwindling antimicrobial drug discovery and developmental program. In this context, we have screened the Library of Pharmacologically Active Compounds (LOPAC, Sigma) against Staphylococcus aureus and Mycobacterium tuberculosis to identify potent novel antimicrobial molecules amongst non-antibiotic molecules. Microplate-based whole cell growth assay was performed to analyze the antimicrobial potency of the compounds against Staphylococcus aureus and Mycobacterium tuberculosis. We identified diphenyleneiodonium chloride, a potent inhibitor of NADH/NADPH oxidase, as a broad-spectrum antibiotic potently active against drug resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis. Intriguingly, the diphenyleneiodonium chloride was also very effective against slow-growing non-replicating Mtb persisters. FIC index demonstrated a strongly synergistic interaction between diphenyleneiodonium chloride and Rifampicin while it did not interact with INH. The antimicrobial property of the diphenyleneiodonium chloride was further validated in vivo murine neutropenic thigh S. aureus infection model. Taken together, these findings suggest that Diphenyleneiodonium chloride can be potentially repurposed for the treatment of tuberculosis and staphylococcal infections.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Repositioning; Drug Synergism; Enzyme Inhibitors; Mice; Microbial Viability; Mycobacterium tuberculosis; NADH, NADPH Oxidoreductases; Onium Compounds; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Tuberculosis

Polypropylene mesh implants are routinely used to repair abdominal wall defects or incisional hernia. However, complications associated with mesh implantation, such as mesh-related infections, can cause serious problems and may require complete surgical removal. Hence, the aim of the present study was the development of a safe and efficient coating to reduce postoperative mesh infections. Biodegradable poly(lactide-co-glycolide acid) microspheres loaded with rifampicin as an antibacterial agent were prepared through single emulsion evaporation method. The particle size distribution (67.93±3.39 μm for rifampicin-loaded microspheres and 64.43±3.61 μm for unloaded microspheres) was measured by laser diffraction. Furthermore, the encapsulation efficiency of rifampicin (61.5%±2.58%) was detected via ultraviolet-visible (UV/Vis) spectroscopy. The drug release of rifampicin-loaded microspheres was detected by UV/Vis spectroscopy over a period of 60 days. After 60 days, 92.40%±3.54% of the encapsulated rifampicin has been continuously released. The viability of BJ fibroblasts after incubation with unloaded and rifampicin-loaded microspheres was investigated using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, which showed no adverse effects on the cells. Furthermore, the antibacterial impact of rifampicin-loaded microspheres and mesh implants, coated with the antibacterial microspheres, was investigated using an agar diffusion model with

Topics: Animals; Anti-Bacterial Agents; Coated Materials, Biocompatible; Delayed-Action Preparations; Drug Liberation; Female; Lactic Acid; Mice; Mice, Inbred C57BL; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polypropylenes; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Mesh; Surgical Wound Infection; Time Factors

Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3-12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16-18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug-drug interactions.

Topics: Adult; Drug Interactions; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Rifampin; Sirolimus; Staphylococcal Infections; Voriconazole

Methicillin resistance among staphylococci isolated from patients in northern Egypt has escalated alarmingly in the past decade. Data about the prevalence of fusidic acid (FA) resistance in Egyptian clinical isolates are limited. This work investigates the prevalence and mechanism of FA resistance among 81 methicillin-resistant staphylococcal isolates from major hospitals of Alexandria, Egypt. Some combinations for treating infections due to resistant isolates were studied. Twenty-six isolates (32.1%) were FA resistant (minimum inhibitory concentrations [MICs] = 2-1,024 μg/ml), and fusB and fusC genes coding for FA resistance were detected in 30.77% and 34.62% of the FA-resistant strains, respectively. One highly resistant isolate, S502 (MIC = 1,024 μg/ml), possessed both genes. Plasmid curing resulted in fusB loss and MIC decrease by 16-64 folds. Conjugation caused acquisition of FA resistance among susceptible isolates. Serial passages in subinhibitory FA concentrations produced mutants with increased MIC by 4-32 folds. The combination of FA with rifampin, gentamicin, or ampicillin/sulbactam, in a subinhibitory concentration, was synergistic against the isolates, including serial passage mutants, decreasing number of survivors by an average of 2-4 logs. A relatively moderate rate of FA resistance was detected in Alexandria hospitals. Combination therapy with gentamicin, rifampin, or ampicillin/sulbactam is crucial to preserve the effectiveness of FA.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Proteins; Conjugation, Genetic; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Egypt; Fusidic Acid; Gene Expression Regulation, Bacterial; Gentamicins; Humans; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Plasmids; Rifampin; Staphylococcal Infections; Sulbactam

Using a tissue cage infection rat model, we test the anti-biofilm effect of clarithromycin on the efficacy of daptomycin and a daptomycin + rifampicin combination against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro: kill curves, daptomycin exposure studies and clarithromycin activity against biofilm were studied. In vivo: the efficacies of clarithromycin, daptomycin or daptomycin + clarithromycin, daptomycin + rifampicin and daptomycin + rifampicin + clarithromycin combinations were evaluated. In vitro: the addition of clarithromycin to daptomycin improved its activity only against one MRSA strain. Changes in daptomycin MIC values appeared more quickly in MSSA than in MRSA strain, and this was not modified by clarithromycin. Clarithromycin prevented biofilm formation but did not eradicate it. In vivo: the daptomycin + rifampicin combination was the most effective treatment and was not improved by the addition of clarithromycin. Daptomycin and daptomycin + clarithromycin had similar effectiveness; the combination protected against the appearance of daptomycin resistance only in one MRSA strain. Using a staphylococcal foreign-body infection model, we observed a slight effect with the addition of clarithromycin to daptomycin, which resulted in protection against the appearance of daptomycin-resistant strains. However, efficacy was not improved. Overall, our findings do not support a relevant clinical role for macrolides in treating device-related staphylococcal infections based on their anti-biofilm effect.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Clarithromycin; Daptomycin; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Foreign Bodies; Microbial Sensitivity Tests; Microbial Viability; Rats; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Topics: Anti-Bacterial Agents; Biofilms; Humans; Orthopedics; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

To explore if combinations of linezolid (L) with rifampicin (R) are able to restrict Staphylococcus aureus resistance, the enrichment of L- and R-resistant mutants was studied in an in vitro dynamic model. L- and R-resistant mutants were enriched in all single drug treatments. In contrast, L-resistant mutants were not enriched and R-resistant mutants were similar to baseline amounts with only minimal regrowth at the end of the combination treatments. These effects appear to be explained by lowering the mutant prevention concentration (MPC) for L+R combinations (MPC

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; In Vitro Techniques; Linezolid; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tissue Distribution

Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Drug Therapy, Combination; Foreign Bodies; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rats, Wistar; Rifampin; Staphylococcal Infections; Vancomycin

Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is poorly described for surgeons, despite the increased exposure to nosocomial pathogens and at-risk patients. This study investigated the molecular epidemiology and antimicrobial resistance of 26 MRSA isolates cultured from the nares of an international cross-sectional study of 1166 human and 60 veterinary surgeons.. All isolates were subjected to agr, spa and multilocus sequence typing, and the presence of 22 virulence factors was screened for by PCR. Additionally, biofilm-forming ability, haemolytic activity, staphyloxanthin production and antibiotic resistance were determined. The genome of a rifampicin-resistant MRSA was sequenced.. Approximately half of the isolates belonged to well-described clonal lineages, ST1, ST5, ST8, ST45 and ST59, that have previously been associated with severe infections and increased patient mortality. Two of the three veterinarian MRSA belonged to epidemic livestock-associated MRSA clonal lineages (ST398 and ST8) previously associated with high transmission potential between animals and humans. The isolates did not display any consistent virulence gene pattern, and 35 % of the isolates carried at least one of the Panton-Valentine leukocidin (lukFS-PV), exfoliative toxin (eta) or toxic shock syndrome (tst) genes. Resistance to rifampicin was detected in one veterinarian isolate and was found to be due to three mutations in the rpoB gene.. Surgeons occupy a critical position in the healthcare profession due to their close contact with patients. In this study, surgeons were found to be colonized with MRSA at low rates, similar to those of the general population, and the colonizing strains were often common clonal lineages.

Topics: Bacterial Toxins; Biofilms; Cross Infection; Cross-Sectional Studies; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Genome, Bacterial; Genotype; Humans; Internationality; Male; Methicillin-Resistant Staphylococcus aureus; Molecular Epidemiology; Multilocus Sequence Typing; Nose; Phenotype; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; Staphylococcal Infections; Surgeons; Veterinarians; Virulence Factors

Rifampicin has received increased interest in veterinary dermatology because of its activity against multidrug-resistant meticillin-resistant staphylococci (MRS). There is limited knowledge about the efficacy and safety of rifampicin in dogs.. To provide information on response to treatment and adverse effects in dogs treated with rifampicin for multidrug-resistant MRS pyoderma.. Thirty two dogs treated with rifampicin for rifampicin-susceptible multidrug-resistant MRS pyoderma.. Retrospective review of medical records, including alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum activity levels and total bilirubin concentrations, obtained before and throughout the treatment, was performed.. Oral rifampicin as sole systemic antimicrobial therapy (median dose 5 mg/kg twice daily) was effective in 71.88% of cases. Topical antimicrobials were used in most cases. Median duration of rifampicin treatment was five weeks for superficial pyoderma and four weeks for deep pyoderma. Gastrointestinal signs were reported in 15% of treated dogs. Statistically significant increases of ALT (P = 0.045) and ALP (P = 0.0002) values after 3-4 weeks of treatment was observed. The median increase was equal to 0.3 and ×1.5 the upper limit of the reference ranges for ALT and ALP, respectively.. Oral rifampicin combined with topical antimicrobials can be considered an effective therapeutic option for canine superficial and deep pyoderma caused by rifampicin-susceptible multidrug-resistant MRS. Liver enzyme induction might be the most important cause of ALT and ALP increase associated with rifampicin therapy in dogs.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Bacterial Agents; Dog Diseases; Dogs; Drug Resistance, Multiple, Bacterial; Female; Male; Methicillin Resistance; Pyoderma; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus

Tedizolid is an orally bioavailable oxazolidinone with once-daily dosing and broad-spectrum Gram-positive activity. Combination therapy is commonly indicated to improve efficacy against difficult-to-treat pathogens and biofilms. There are no studies describing the pharmacodynamic interactions between tedizolid and other orally bioavailable antimicrobials.. MICs of tedizolid, rifampicin, trimethoprim/sulfamethoxazole, doxycycline and moxifloxacin were determined by broth microdilution against a convenience sample of 45 staphylococcal isolates. Seven MRSA isolates and three Staphylococcus epidermidis were evaluated by time-kill using concentrations equal to 0.5× the MIC. These strains had variable susceptibility to the investigated antimicrobials. Synergy was defined as a ≥2 log 10 cfu/mL reduction of the combination over the most active single agent, antagonism was defined as ≥1 log 10 cfu/mL growth compared with the most active single agent, and other interactions were indifferent.. Three of 45 strains tested were non-susceptible to tedizolid (MIC = 1 mg/L), but the MIC 90 was 0.5 mg/L. Interactions between tedizolid and other agents were largely indifferent (80%). Tedizolid was synergistic with doxycycline and rifampicin against 2/10 and 3/10 strains, respectively. Tedizolid was antagonistic with moxifloxacin against 3/10 strains. Other interactions were indifferent.. The addition of rifampicin to tedizolid appears to be the most likely to improve activity but synergy was not universal. The combination of tedizolid plus moxifloxacin should be avoided due to the risk of antagonism. The addition of other orally bioavailable anti-staphylococcal agents to tedizolid may be unlikely to improve killing but further research is warranted to assess the impact of these combinations on resistance prevention, or against biofilm-embedded organisms.

Topics: Acetamides; Administration, Oral; Anti-Bacterial Agents; Drug Interactions; Fluoroquinolones; Humans; Kinetics; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Tetrazoles; Trimethoprim, Sulfamethoxazole Drug Combination

Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection.. We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity.. Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin.. Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection.

Topics: Anti-Bacterial Agents; Cost-Benefit Analysis; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Biofilm formation leads to the failure of antimicrobial therapy. Thus, biofilm prevention is a desirable goal of antimicrobial research. In this study, the efficacy of antibiotics (doxycycline, oxacillin and rifampicin) in preventing Staphylococcus aureus biofilms was investigated using Microtiter Well Plates (MWP) and Drip Flow Reactors (DFR), two models characterized by the absence and the presence of a continuous flow of nutrients, respectively. Planktonic culture of S. aureus was exposed to antibiotics for one hour followed by 24 hours incubation with fresh nutrients in MWP or continuous flow of nutrients in DFR. The DFR grown biofilms were significantly more tolerant to the antibiotics than those grown in MWP without the continuous flow. The differences in log reductions (LR) between the two models could not be attributed to differences in the cell density, the planktonic inoculum concentration or the surface-area-to-volume ratios. However, eliminating the flow in the DFR significantly restored the antibiotic susceptibility. These findings demonstrate the importance of considering differences between experimental conditions in different model systems, particularly the flow of nutrients, when performing anti-biofilm efficacy evaluations. Biofilm antibiotic efficacy studies should be assessed using various models and more importantly, in a model mimicking conditions of its clinical application.

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Biofilms; Doxycycline; Humans; Microbial Sensitivity Tests; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus aureus

This study was conducted to compare the mutation rates of different rpoB sites and rifampin minimum inhibitory concentration (MIC) changes prior to and after rifampin therapy for biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) isolates.. The screening of rifampin-resistant MRSA isolates, from the biofilm at Day 5 with or without exposure to the susceptible breakpoint concentration of rifampin recommended by the Clinical and Laboratory Standards Institute (1 mg/L), was conducted using agar plates containing rifampin. A partial fragment of RNA polymerase B subunit gene (rpoB), including clusters I and II, was amplified and sequenced. The rifampin MIC values and mutation frequencies at different sites of rpoB were measured and evaluated in rifampicin-resistant isolates.. Rifampin-resistant mutants could be selected from all of 39 randomly selected rifampin-susceptible MRSA isolates in the biofilm model. The spontaneous mutation frequency ranged from 1.00 × 10(-4) to 3.85 × 10(-7). Mutation at codon 481 was most commonly found at 35 (89.7%) of 39 MRSA isolates. Without rifampin induction, the MIC ranged between 0.125 mg/L and1024 mg/L and mutation sites included cluster I 464, 466, 468, 471, 474, 477, 481, 484, 486 and cluster II 519, 527, 529 with the percentage of 471 (35.9%), 477 (33.3%), 481 (53.8%), and 484 (35.9%). Conversely, with the induction of rifampin, the MIC value ranged ∼256-1024 mg/L. The mutation sites that were more concentrated included 468 (17.9%), 477 (30.8%), 481 (89.7%), 484 (17.9%), and 486 (33.3%).. We documented high rifampin resistance induction activity when MRSA was engaged in biofilm with rifampin exposure. Monotherapy seems to be inadequate for MRSA in biofilm. There is an urgent need for developing effective combination therapies with less rifampin resistance-inducing activities for treating MRSA in biofilms.

Topics: Anti-Bacterial Agents; Base Sequence; Biofilms; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mutation; Rifampin; RNA Polymerase II; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Clindamycin; Female; Humans; Male; Osteoarthritis; Rifampin; Serum; Staphylococcal Infections

Hepatotoxicity due to anti tuberculosis drugs, rifampin and isoniazid, is a major problem in tuberculosis patients. Vitamin C, an antioxidant, and N-acetyl cysteine (NAC), a scavenger of active metabolites, reduce the hepatotoxicity. The aim of present study was to investigate the effect of vitamin C and NAC individually on the antibacterial activity of anti tuberculosis drugs against Mycobacterium tuberculosis and Staphylococcus aureus strains.. The MICs of each compound against all strains were determined in 96 wells plate. Rifampin was tested at serial two fold concentrations alone or in combination with NAC or vitamin C.. The MIC of rifampin against different strains of S. aureus was 0.008-0.032 μg/ml. The MIC of rifampin and isoniazid against M. tuberculosis strains were 40 and 0.2 μg/ml, respectively. Vitamin C and NAC had no antibacterial activity against all strains. MIC of rifampin was reduced two fold by combination with vitamin C for all S. aureus strains, while NAC did not affect the antibacterial activity of rifampin. Vitamin C and NAC had remarkable effects on the antibacterial activity of anti-tuberculosis drugs against M. tuberculosis.. Synergistic effects were observed between rifampin or isoniazid and vitamin C against all tested strains. However, combination therapy of rifampin and isoniazid with NAC was not being effective. This study highlighted the advantages of combination of anti-tuberculosis drugs and vitamin C to eradicate the microbial infections.

Topics: Acetylcysteine; Antitubercular Agents; Ascorbic Acid; Drug Synergism; Drug Therapy, Combination; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Previously, we investigated a locally developed technique of bonding arterial grafts with three antimicrobials to protect against early (within 2 weeks) perioperative bacterial contamination encountered occasionally during aortic graft prosthetic reconstruction. Vascular graft infections are classified by their appearance time (early [<4 months] vs late [>4 months] after graft implantation), degree of incorporation into the surrounding vessel wall, connectivity to the postoperative wound, and extent of graft involvement. In the current phase of testing, we evaluated the ability of our novel triple antimicrobial-bonded graft to prevent infection in the first 8 weeks after implantation.. At week 9, all of the grafts were explanted. All S aureus-inoculated bonded grafts (n = 5) showed no bacterial growth. The unbonded, uninoculated graft (n = 1) showed low-level bacterial growth (<1.2 × 10. Our triple-bonded aortic graft prevented perioperative aortic graft infection for at least 8 weeks in a porcine model. The synergistic antimicrobial activity of this graft was sufficient to prevent and/or eradicate infection during that period. Further studies are needed to assess the graft's ability to combat early-onset vascular graft infection for up to 4 months.

Topics: Animals; Anti-Infective Agents; Aorta, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chlorhexidine; Coated Materials, Biocompatible; Disease Models, Animal; Minocycline; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Swine; Swine, Miniature; Time Factors

Staphylococcus aureus small-colony variants (SCVs) emerge frequently during chronic infections and are often associated with worse disease outcomes. There are no standardized methods for SCV antibiotic susceptibility testing (AST) due to poor growth and reversion to normal-colony (NC) phenotypes on standard media. We sought to identify reproducible methods for AST of S. aureus SCVs and to determine whether SCV susceptibilities can be predicted on the basis of treatment history, SCV biochemical type (auxotrophy), or the susceptibilities of isogenic NC coisolates. We tested the growth and stability of SCV isolates on 11 agar media, selecting for AST 2 media that yielded optimal SCV growth and the lowest rates of reversion to NC phenotypes. We then performed disk diffusion AST on 86 S. aureus SCVs and 28 isogenic NCs and Etest for a subset of 26 SCVs and 24 isogenic NCs. Growth and reversion were optimal on brain heart infusion agar and Mueller-Hinton agar supplemented with compounds for which most clinical SCVs are auxotrophic: hemin, menadione, and thymidine. SCVs were typically nonsusceptible to either trimethoprim-sulfamethoxazole or aminoglycosides, in accordance with the auxotrophy type. In contrast, SCVs were variably nonsusceptible to fluoroquinolones, macrolides, lincosamides, fusidic acid, and rifampin; mecA-positive SCVs were invariably resistant to cefoxitin. All isolates (both SCVs and NCs) were susceptible to quinupristin-dalfopristin, vancomycin, minocycline, linezolid, chloramphenicol, and tigecycline. Analysis of SCV auxotrophy type, isogenic NC antibiograms, and antibiotic treatment history had limited utility in predicting SCV susceptibilities. With clinical correlation, this AST method and these results may prove useful in directing treatment for SCV infections.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Fluoroquinolones; Fusidic Acid; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.

Topics: Aged; Anti-Bacterial Agents; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Knee; Linezolid; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Patella; Rifampin; Staphylococcal Infections

There is increasing clinical evidence from observational studies, that combination therapy of daptomycin with rifampin is a valuable treatment option for biofilm-associated difficult to treat Staphylococcus aureus infections such as osteomyelitis, prosthetic joint infection and endocarditis. However, two studies analyzing a limited number of S. aureus isolates reported an antagonism of those two drugs questioning the benefit of this combination.. To estimate the frequency of this possible antagonism, we performed in vitro checkerboard assays on 58 consecutive clinical isolates of S. aureus (MSSA n = 9, MRSA n = 49). We determined the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). All isolates were characterized by a microprobe array detecting 336 different genes/alleles to ensure their non-clonal origin.. For all isolates, the FICI was between 1.00 and 1.25 indicating additive effects for the daptomycin/rifampin combination. Neither antagonism nor synergism as defined by the FICI was found for any of the isolates.. Based on these data, there is no evidence to advise against the daptomycin/rifampin combination therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child, Preschool; Daptomycin; Drug Antagonism; Female; Humans; Infant; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Young Adult

Prosthetic vascular graft infection (PVGI) is an emerging disease, mostly caused by staphylococci, with limited data regarding efficacy of current antistaphylococcal agents. We aimed to assess the efficacy of different antibiotic regimens.. Six different strains of MSSA and MRSA were used. We compared results of minimal biofilm inhibitory and eradicating concentrations (MBICs and MBECs) obtained with a Calgary Biofilm Pin Lid Device (CBPD) with those yielded by an original Dacron(®)-related minimal inhibitory and eradicating concentration measure model. We then used a murine model of Staphylococcus aureus vascular prosthetic material infection to evaluate efficacy of different antibiotic regimens: vancomycin and daptomycin combined or not with rifampicin for MRSA and the same groups with cloxacillin and cloxacillin combined with rifampicin for MSSA.. We demonstrated that classical measures of MBICs and MBECs obtained with a CPBD could overestimate the decrease in antibiotic susceptibility in material-related infections and that the nature of the support used might influence the measure of biofilm susceptibility, since results yielded by our Dacron(®)-related minimal eradicating assay were lower than those found with a plastic device. In our in vivo model, we showed that daptomycin was significantly more bactericidal than comparators for some strains of MRSA or MSSA but not for all. For the majority of strains, it was as efficient as comparators. The addition of rifampicin to daptomycin did not enhance daptomycin efficacy.. Despite the heterogeneity of results according to bacterial strains, these innovative models represent an option to better evaluate the in vitro efficacy of antibiotics on Dacron(®)-related biofilm S. aureus infections, and to screen different antibiotic regimens in a mouse model of PVGIs.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Models, Biological; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

The aim of the present study was to assess the in vitro anti-biofilm activities of solid lipid nanoparticles (SLN) loaded with rifampin against biofilm-producing Staphylococcus epidermidis.. SLN were prepared and characterized for size, zeta potentials and encapsulation efficacy. The morphological and thermal properties of formulation were evaluated by TEM imagining and DSC analysis. The anti-biofilm activity of different formulations was assessed at different incubation times and concentrations by crystal violet (CV) and viable biofilm count methods.. The zeta potentials, particle sizes and encapsulation efficiencies of final formulations were 17 ± 0.7 mV, 101 ± 4.7 nm and approximately 70%; respectively. Rifampin-SLN was able to reduce the biomass of biofilm at time- and concentration-dependent manner. According to biofilm count results, the Rifampin-SLN was more effective for removal of the bacteria with respect to free rifampin.. The results of this study highlight the advantages and efficiency of Rifampin-SLN in biofilm eradication.

Topics: Anti-Bacterial Agents; Biofilms; Drug Carriers; Drug Compounding; Humans; Lipids; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Rifampin is recommended as adjunctive treatment for staphylococcal prosthetic valve endocarditis (PVE). It is unclear whether this should hold for surgically treated patients. The purpose of this study was to examine whether adjunctive rifampin treatment in addition to cell wall active antimicrobial agents in patients with surgically treated staphylococcal infective endocarditis (IE) results in better outcomes.. Patients operated on for staphylococcal IE from April 1, 2008, to July 1, 2014, were identified from our institution's IE registry. Rifampin treatment was defined as 3 or more days of rifampin postoperatively. Cox proportional hazards regression was used to compare a composite outcome of death or reoperation for IE relapse, between patients treated and not treated with rifampin, adjusted for propensity to be treated with rifampin, methicillin resistance, all-purpose refined diagnosis related group (APR-DRG) severity score, and APR-DRG mortality risk.. In all, 273 patients were identified. The mean age was 56 years, 66% were male, 50% had PVE, 60% had S. aureus or S. lugdunensis infection, 89% had left side involvement, and 57% had invasive disease. Fifty-one (27%) received 3 or more days of rifampin postoperatively. Ninety-two patients died or underwent reoperation for IE relapse at a median of 205 days (interquartile range 56 to 718 days). In a multivariable model, patients treated with rifampin had a similar hazard of death or reoperation for IE relapse as those not treated (hazard ratio 0.76, 95% confidence interval 0.44 to 1.32, p value 0.34). The results were robust to varying definitions of rifampin treatment.. Among patients with surgically treated staphylococcal IE there was insufficient evidence to claim a reoperation-free survival benefit from treatment with rifampin. Rifampin should not be used as adjunctive therapy for staphylococcal IE in patients who have undergone surgical procedures for its treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Drug Evaluation; Endocarditis, Bacterial; Female; Follow-Up Studies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Practice Guidelines as Topic; Propensity Score; Proportional Hazards Models; Recurrence; Reoperation; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus lugdunensis; Treatment Failure

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Osteomyelitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important pathogens in the hospital environment. Monitoring of this pathogen by molecular characterization and phenotypic methods is important for the development of suitable infection control measures and proper therapy design. In this study, our aim was to investigate the molecular epidemiological characteristics of MRSA bloodstream isolates obtained from patients hospitalized at Ankara University Ibn-i Sina Hospital in a 10-year period (2002-2012) and monitor the possible changes. A total of 134 isolates were characterized according to their antimicrobial susceptibility profiles, biofilm formation capabilities, accessory gene regulator (agr) locus types, presence of genes encoding Panton-Valentine leukocidin (PVL), staphylococcal enterotoxins A-J (SEs A-J), toxic shock syndrome toxin, sasX, and genes associated with biofilm formation (icaD, icaA, IS256) by polymerase chain reaction. The staphylococcal cassette chromosome mec (SCCmec) types of isolates were also defined and their clonal relationships were investigated by pulsed-field gel electrophoresis (PFGE) analysis and multilocus sequence typing was performed for representative isolates obtained by PFGE.. The majority of the isolates were resistant to rifampin (100%), ciprofloxacin (97%), tetracycline (97.7%), and gentamicin (94.7%); 100% carried type-III SCCmec and 89.5% were agr type-1. All the isolates were negative for PVL, and sasX genes while all of them carried the icaD, icaA, and IS256 genes. The most common SE was enterotoxin A (97%). Four major PFGE patterns with the dominance of one pattern and seven unique patterns were obtained. All the representative PFGE isolates (n = 11) belonged to sequence type 239.. We have documented the characteristics of the dominant MRSA clone in our hospital, which was a PVL (-), sasX (-) ST239 clone carrying sea (+) with type-III SCCmec, and type-1 agr locus.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Chromosomes, Bacterial; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Genetic Loci; Gentamicins; Hospitals, University; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Epidemiology; Phylogeny; Retrospective Studies; Rifampin; Staphylococcal Infections; Tetracycline; Turkey

Rifampicin encapsulated microparticles were designed for intraocular injection after cataract surgery to prevent postoperative endophthalmitis. Microparticles were formulated by emulsification diffusion method using poly(lactic acid-co-glycolic acid) (PLGA) as polymer in order to propose a new form of rifampicin that overcome its limitations in intraocular delivery. Depending on processing formulation, different types of microparticles were prepared, characterized and evaluated by in vitro release studies. Two types of microparticles were selected to get a burst release of rifampicin, to reach minimal inhibitory concentrations to inhibit 90% of Staphylococcus epidermidis mainly involved in postoperative endophthalmitis, combined with a sustained release to maintain rifampicin concentration over 24h. The antibacterial activity and antiadhesive property on intraocular lenses were evaluated on S. epidermidis. Microparticles, with a rapid rifampicin release profile, showed an effect towards bacteria development similar to free rifampicin over 48h. However, slow-release profile microparticles exhibited a similar antibacterial effect during the first 24h, and were able to destroy all the S epidermidis in the medium after 30h. The association of the two formulations allowed obtaining interesting antibacterial profile. Moreover, rifampicin-loaded microparticles have shown a very efficient anti-adherent effect of S. epidermidis on intraocular lenses at 24h. These results propose rifampicin microparticles as suitable for antibioprophylaxis of the postoperative endophthalmitis.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Liberation; Endophthalmitis; Lactic Acid; Microbial Sensitivity Tests; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Time Factors

The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model.. Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density. A maximum effect model was used to determine the PK/PD index that best described the dose-response data.. The area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96; Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose fractionation-response study did not show significantly different antimicrobial activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA) with MIC of 128 μg/mL or more.. Rifampicin demonstrated concentration-dependent killing. The AUC/MIC was a predictive PK/PD index.

Topics: Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred ICR; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Thigh

Susceptibility to antibiotics is dramatically reduced when bacteria form biofilms. In clinical settings this has a profound impact on treatment of implant-associated infections, as these are characterized by biofilm formation. Current routine susceptibility testing of microorganisms from infected implants does not reflect the actual susceptibility, and the optimal antibiotic strategy for treating implant-associated infections is not established. In this study of biofilm formation in implant-associated osteomyelitis, we compared thein vitroandin vivoefficacy of selected antibiotics alone and in combination againstStaphylococcus aureus.We tested vancomycin, linezolid, daptomycin and tigecycline alone and in combination with rifampicin, vancomycin, linezolid and daptomycin againstS. aureusIn vitro, biofilm formation dramatically reduced susceptibility by a factor of 500-2000.In vivo, antibiotic combinations were tested in a murine model of implant-associated osteomyelitis. Mice were infected by inserting implants colonized withS. aureustrough their tibia. After 11 days, the animals were divided into different groups (five animals/group) and given 14 days of antibiotic therapy. All antibiotics resulted in a reduced bacterial load in the infected bone surrounding the implant. Overall, the most effective antibiotic combinations contained rifampicin. Combinations containing two non-rifampicin antibiotics were not more active than single drugs.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Daptomycin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Linezolid; Mice; Microbial Sensitivity Tests; Osteomyelitis; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Linezolid is a valuable treatment option for treating infections caused by multi-resistant gram-positive pathogens. Lack of effective linezolid levels due to the co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this potential drug interaction (DI) for critically ill patients is still unclear. This was a retrospective analysis of 3 critically ill patients with the combination therapy of linezolid and rifampicin or rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority of observed linezolid trough concentrations in all 3 patients were below 2 mg/l. Furthermore, linezolid trough concentrations remained below 2 mg/l after discontinuation of rifampicin. This potential DI between linezolid and rifampicin could lead to treatment failure. Therefore, we strongly recommend that linezolid serum concentrations be monitored in patients with rifampicin co-administration or rifampicin pretreatment.

Topics: Aged; Anti-Bacterial Agents; Critical Illness; Drug Interactions; Drug Therapy, Combination; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

We report the successful use of daptomycin in a child with methicillin-resistant Staphylococcus aureus endocarditis with persistent bacteremia and clinical deterioration, despite treatment with vancomycin and rifampicin. She had acute kidney injury, requiring daptomycin dosage adjustment.

Topics: Anti-Bacterial Agents; Bacteremia; Child, Preschool; Daptomycin; Endocarditis, Bacterial; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf).. Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001-2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf.. A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P <0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 - 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf.. The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions.

Topics: Adult; Anti-Bacterial Agents; Australia; Cross Infection; Cross-Sectional Studies; Cystic Fibrosis; Female; Fusidic Acid; Health Personnel; Humans; Incidence; Linezolid; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Multivariate Analysis; Retrospective Studies; Rifampin; Staphylococcal Infections; Treatment Outcome; Young Adult

Staphylococcus aureus is one of the main etiologies of bone and device-related infections. Treatment of these orthopedic infections combines mostly rifampicin with other antibiotics. The recurrence or failure rate after fusidic acid/rifampicin treatment remains low (<10%). We discuss here a case of antibiotic treatment failure for Staphylococcus aureus bone infection with in vivo selection of rifampicin and fusidic acid resistance. We also report a new mutation in fusA gene involved in fusidic acid resistance.

Topics: Adolescent; Anti-Bacterial Agents; Bone Diseases, Infectious; Drug Resistance, Bacterial; Fusidic Acid; Humans; Male; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coronary Restenosis; Drainage; Drug Therapy, Combination; Emergencies; Humans; Male; Middle Aged; Myocardial Infarction; Pericardial Effusion; Pericarditis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Stents; Teicoplanin

We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bone Wires; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Foreign Bodies; Injections, Intraperitoneal; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Organophosphates; Osteomyelitis; Oxazoles; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tibia; Vancomycin

The aim of this study was to assess the characteristics of periprosthetic joint infection (PJI) due to Staphylococcus lugdunensis and to compare these to the characteristics of PJI due to Staphylococcus aureus and Staphylococcus epidermidis.. A retrospective multicentre study including all consecutive cases of S. lugdunensis PJI (2000-2014) was performed. Eighty-eight cases of staphylococcal PJI were recorded: 28 due to S. lugdunensis, 30 to S. aureus, and 30 to S. epidermidis, as identified by Vitek 2 or API Staph (bioMérieux).. Clinical symptoms were more often reported in the S. lugdunensis group, and the median delay between surgery and infection was shorter for the S. lugdunensis group than for the S. aureus and S. epidermidis groups. Regarding antibiotic susceptibility, the S. lugdunensis strains were susceptible to antibiotics and 61% of the patients could be treated with levofloxacin + rifampicin. The outcome of the PJI was favourable for 89% of patients with S. lugdunensis, 83% with S. aureus, and 97% with S. epidermidis.. S. lugdunensis is an emerging pathogen with a pathogenicity quite similar to that of S. aureus. This coagulase-negative Staphylococcus must be identified precisely in PJI, in order to select the appropriate surgical treatment and antibiotics .

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Joint Prosthesis; Levofloxacin; Male; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus lugdunensis; Treatment Outcome

Ustekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so far.. Here, we report the case of a 64-year old woman presenting with chills, pain and swelling of her right foot with dark maculae at the sole, and elevated inflammatory markers. She had received a third dose of ustekinumab due to psoriatic arthritis three days before admission. Blood cultures revealed growth of Staphylococcus aureus and imaging showed a thickening of the aortic wall ventral the bifurcation above the right internal iliac artery, resembling an acute bacterial endarteritis. Without the evidence of aneurysms and in absence of foreign bodies, the decision for conservative management was made. The patient received four weeks of antibiotic therapy with intravenous flucloxacillin, followed by an oral regime with levofloxacin and rifampicin for an additional four weeks. Inflammatory markers resolved promptly and the patient was discharged in good health.. To our knowledge, this is the first report of a severe S. aureus infection in a patient receiving ustekinumab. Albeit ustekinumab is generally regarded as a safe drug, severe bacterial infections should always be included in the differential diagnosis of elevated inflammatory markers in patients receiving biologicals as these might present with nonspecific symptoms and fever might be absent. Any effort to detect deep-seated or metastatic infections should be made to prevent complications and to secure appropriate treatment. Although other risk factors for an invasive staphylococcal infection like psoriasis, recent corticosteroid injection, or prior hospitalisations were present, and therefore a directive causative link between the S. aureus bacteraemia and ustekinumab can not be drawn, we considered the reporting of this case worthwhile to alert clinicians as we believe that ongoing pharmacovigilance to detect increased risks for rare but severe infections beyond phase II and phase III trials in patients treated with biologicals is essential.

Topics: Administration, Intravenous; Administration, Oral; Arthritis, Psoriatic; Bacteremia; Dermatologic Agents; Endarteritis; Female; Floxacillin; Humans; Iliac Artery; Levofloxacin; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Ustekinumab

The objective of this study was to evaluate the antimicrobial performance of a rifampin/minocycline-coated, non-cross-linked, acellular porcine dermal matrix (XenMatrix AB) compared to an uncoated, non-cross-linked, acellular porcine dermal matrix (Strattice) after implantation/inoculation with methicillin-resistant Staphylococcus aureus or Escherichia coli in a dorsal rabbit model.. Forty male New Zealand White rabbits were bilaterally implanted with XenMatrix AB or Strattice grafts and inoculated with clinically isolated methicillin-resistant S. aureus (5 × 10 colony-forming units/ml) or E. coli (1 × 10 colony-forming units/ml). At 2 and 8 weeks, sites were analyzed for viable methicillin-resistant S. aureus/E. coli colony-forming units, abscess formation, and histologic response (n = 5 rabbits per group per bacterium per time point).. XenMatrix AB completely inhibited bacterial colonization of the graft, inhibited abscess formation, reduced inflammation and encapsulation, and improved neovascularization compared with Strattice. XenMatrix AB implants exhibited significantly fewer colony-forming units compared with Strattice implants at 2 weeks (methicillin-resistant S. aureus) (p < 0.01) and at 2 and 8 weeks (E. coli) (p < 0.05). In addition, XenMatrix AB implants demonstrated a significantly lower abscess score at 2 weeks (methicillin-resistant S. aureus) and 8 weeks (E. coli) (p < 0.01 in both cases). For both types of bacteria and both time points evaluated, XenMatrix AB implants exhibited minimal inflammation and encapsulation and a lack of neutrophils. In contrast, Strattice implants displayed marked inflammatory and neutrophilic responses and moderate encapsulation.. This study demonstrated the antimicrobial performance of a rifampin/minocycline-coated bioprosthetic (XenMatrix AB) in a rabbit inoculation model. XenMatrix AB completely inhibited bacterial colonization of the graft, with minimal host inflammation and encapsulation, and improved neovascularization compared with Strattice.

Topics: Acellular Dermis; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Escherichia coli Infections; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Rabbits; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Swine; Treatment Outcome

Coagulase-negative staphylococci (CoNS) are opportunistic pathogens that particularly cause infections in patients with implanted medical devices. The present research was performed to study the virulence potential of 53 clinical isolates of Staphylococcus capitis, Staphylococcus auricularis, Staphylococcus lugdunensis, Staphylococcus simulans, Staphylococcus cohnii and Staphylococcus caprae. All clinical strains were clonally unrelated. Isolates carried genes encoding resistance to β-lactam (mecA) (15 %), aminoglycoside [aac(6')/aph(2″)(11 %), aph (3')-IIIa (15 %), ant(4')-Ia (19 %)] and macrolide, lincosamide and streptogramin B (MLSB) [erm(A) (4 %), erm(B) (13 %), erm(C) (41 %), msr(A) (11 %)] antibiotics. CoNS isolates (64 %) were able to form biofilms. Confocal laser scanning microscopy revealed that these biofilms formed a three-dimensional structure composed mainly of living cells. All biofilm-positive strains carried the ica operon. In vitro studies demonstrated that a combination treatment with tigecycline and rifampicin was more effective against biofilms than one with ciprofloxacin and rifampicin. The minimum biofilm eradication concentration values were 0.062-0.5 µg ml-1 for tigecycline/rifampicin and 0.250-2 µg ml-1 for ciprofloxacin/rifampicin. All CoNS strains adhered to the human epithelial cell line HeLa, and more than half of the isolates were able to invade the HeLa cells, although most invaded relatively poorly. The virulence of CoNS is also attributed to their cytotoxic effects on HeLa cells. Incubation of HeLa cells with culture supernatant of the CoNS isolates resulted in cell death. The results indicate that the pathogenicity of S. capitis, S. auricularis, S. lugdunensis, S. cohnii and S. caprae is multi-factorial, involving the ability of these bacteria to adhere to human epithelial cells, form biofilms and invade and destroy human cells.

Topics: Aminoglycosides; Anti-Bacterial Agents; Biofilms; Coagulase; Drug Resistance, Multiple, Bacterial; HeLa Cells; Humans; Lincosamides; Microbial Sensitivity Tests; Operon; Rifampin; Staphylococcal Infections; Staphylococcus; Virulence

Complications associated with the lacrimal Lester Jones tube have been reported. The infections associated with the tube and proper treatment are not well known. The authors have introduced a successful treatment regimen for persistent methicillin-resistant Staphylococcus aureus (MRSA) periocular infection associated with the lacrimal Lester Jones tube without tube removal.. Retrospective case series.. Six patients with MRSA infection associated with the Lester Jones tube without tube removal.. Four patients had improper tube position with total regurgitation and 2 patients had relative normal tube position with a partial to normal passage, but the tube tip irritated the nasal mucosa wound persistently. In all 6 cases, development of a biofilm on the tube was observed. All cultures were positive for MRSA.. All patients were prescribed a combination therapy of topical ocular vancomycin and oral rifampicin before or after the dislocated tube reposition. Periocular symptoms resolved within 1 week, and the biofilm on the tube was gradually reduced during combination therapy. Signs of recurrence of infection were not noted during the follow-up visits.. Patients showing infection signs associated with the Jones tube need to be examined before complete removal of the infected tube. Medical treatment with vancomycin eye drops combined with oral rifampicin for persistent MRSA infection associated with the Lester Jones tube produced a successful result. Removal of the biofilm on the tube at follow-up visits is important to prevent micro-organisms from dispersing around the tissue. If the Jones tube is dislocated, repositioning is highly recommended to prevent periocular MRSA infection recurrence.

Topics: Aged; Anti-Bacterial Agents; Biofilms; Dacryocystorhinostomy; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Humans; Intubation; Lacrimal Duct Obstruction; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Ophthalmic Solutions; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Effective microbiogical eradication of methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) can be obtained, but its effect is not always clear-cut in terms of spirometric indices. The aim of this observational prospective cohort study was to study the potential effect of eradication of chronic MRSA infection on lung function including ventilation distribution. Six CF patients, chronically colonized with MRSA (median age: 21 years (range 14-46); median FEV1: 76 (95%CI 58-98)%pred) were successfully eradicated using oral rifampicin and fusidic acid in combination with topical decolonization measures. Lung function and multiple breath washout test were performed at the start and at the end of the eradication protocol and after an average follow-up period of 7·5±1·5(SD) months. One patient cultured MRSA again 4 months after successful eradication. All patients reported reduced sputum production and viscosity. By the end of the follow-up period, there was an increase in ventilated FRCMBW and no change in plethysmographic FRCPL. This resulted in a significant decrease of trapped air by half a litre (from 579 to 40 ml; P = 0·013). Lung clearance index (LCI) also showed a small but significant decrease (from 7·2 to 6·7; P = 0·014) after eradication of MRSA. We conclude that MRSA eradication can be successful, also in terms of recruitment of previously unventilated air spaces, potentially due to reduced sputum production and/or viscosity.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cystic Fibrosis; Fusidic Acid; Humans; Lung; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prospective Studies; Respiratory Function Tests; Rifampin; Staphylococcal Infections; Young Adult

The purpose of this study was to characterize the utilization of antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations (PEx).. An anonymous national cross-sectional survey of CF Foundation accredited care programs was performed using an electronic survey tool.. Fifty-eight percent (152/261) CF Foundation accredited programs completed the survey. Ninety-eight percent (149/152) of respondents reported using antibiotics (oral or intravenous) against MRSA. Variability exists in the use of antibiotics amongst the programs and in the dosages utilized. For oral outpatient treatment, sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten percent of reported to use it in combination with rifampin. For inpatient treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized in both pediatric (IV 35/224, 16%; oral 41/224, 18%), and adult (IV 44/235, 19%; oral 38/235, 16%) respondents for inpatient treatment. IV vancomycin was the second most commonly utilized antibiotic by pediatric (70/224, 31%) and adult (71/235, 30%) respondents. Most respondents reported dose titration to achieve a vancomycin trough level of 15-20 mg/L (150/179, 84%). Topical or inhaled antibiotic utilization was reported to be an uncommon practice with approximately 70% of pediatric and adult respondents reporting to use them either rarely or never. The concomitant use of anti-MRSA and anti-pseudomonal antibiotics was common with 96% of pediatric and 99% of adult respondents answering in the affirmative.. We conclude that anti-MRSA antibiotics are utilized via various dosage regimens by a majority of CF Foundation accredited care programs for the treatment of chronic MRSA in PEx, and there is no consensus on the best treatment approach.

Topics: Adult; Anti-Bacterial Agents; Child; Cross-Sectional Studies; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Health Care Surveys; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Practice Patterns, Physicians'; Rifampin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement.. MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50 mg/kg every 12 h, tigecycline 14 mg/kg every 12 h, rifampin 25 mg/kg every 12 h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days.. MRSA was cultured from all tibias in the control group (median, 6.06 log10 CFU/g bone). Median bacterial counts (log10 CFU/g) at 48 h post-treatment were 6.16 for vancomycin (p = 0.753), 2.29 for vancomycin plus rifampin (p < 0.001), 5.90 for tigecycline (p = 0.270), 0.10 for tigecycline plus rifampin (p < 0.001), and 0.91 for rifampin (p = 0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment.. Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Male; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Osteomyelitis; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Vancomycin

Biofilm-associated bacteria display a decreased susceptibility towards antibiotics. Routine assessment of antibiotic susceptibility of planktonic bacteria therefore offers an insufficient prediction of the biofilm response. In this study, in vitro biofilms of eight clinical Staphylococcus epidermidis strains were subjected to treatment with vancomycin, teicoplanin, oxacillin, rifampicin and gentamicin. In addition, the biofilms were subjected to combinations of an antibiotic with rifampicin. The effects on the biofilms were assessed by crystal violet staining to determine the total biofilm biomass, staining with XTT to determine bacterial cell viability, and microscopy. Combining these methods showed that treatment of S. epidermidis biofilms with glycopeptides increased the total biofilm biomass and that these antibiotics were not effective in killing bacteria embedded in biofilms. The decreased killing efficacy was more pronounced in biofilms produced by strains that were classified as 'strong' biofilm producers. Rifampicin, oxacillin and gentamicin effectively killed biofilm-associated bacteria of all tested strains. Combining antibiotics with rifampicin increased the killing efficacy without influencing the total biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin, the increase in biofilm biomass was neutralised and also the killing efficacy was influenced in a positive way. We conclude that the combined methodology used in this study showed that glycopeptides were not effective in eradicating S. epidermidis biofilms but that combination with rifampicin improved the killing efficacy in vitro.

Topics: Anti-Bacterial Agents; Biofilms; Drug Interactions; Gentamicins; Humans; Microbial Viability; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin; Vancomycin

The 'soak and smear' regimen is a highly effective method for localised topical therapy employed by dermatologists for widespread inflammatory skin conditions. The regimen involves application of topical medication under occlusion after soaking in water. Complications from this treatment method are rare. We present a case of multiple, generalised methicillin-resistant Staphylococcus aureus (MRSA)-positive furuncles arising in a patient as an unexpected consequence of therapy. The case highlights an unanticipated risk of a commonly employed treatment amid an epidemic of MRSA in the community.

Topics: Aged; Anti-Bacterial Agents; Chlorhexidine; Clobetasol; Diagnosis, Differential; Doxycycline; Eczema; Furunculosis; Glucocorticoids; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Water

Mycotic thoracic aortic aneurysms are a life-threatening diagnosis and carry a high risk of morbidity and mortality in the perioperative setting. Traditional open repair consists of debridement, drainage, and either in situ or extra-anatomic bypass. Acute rupture portends a dismal prognosis; however, emergent endovascular repair of ruptured mycotic aneurysms has been described in the literature and we present a case of successful endovascular treatment of a ruptured mycotic descending thoracic aortic aneurysm.. We report the case of a 42-year-old male with hypertension and active intravenous drug use who presented with 3 weeks of chest pain, dyspnea, and hemoptysis, and on computed tomography scan was found to have a contained 4.1-cm ruptured mycotic thoracic aortic aneurysm. Blood cultures were positive for methicillin-resistant Staphylococcus aureus. Emergent repair was recommended because of likelihood of further rupture and death. Thoracic endovascular aortic repair (TEVAR) was performed using a rifampin-soaked stent graft without complication. At 2-year follow-up, the patient was asymptomatic and imaging demonstrated the stent graft in excellent position, without endoleak, and complete resolution of the aneurysm sac.. TEVAR can be safely employed to treat a ruptured mycotic thoracic aneurysm when open repair is not possible because of patient's comorbidity or complex rupture, as these patients face imminent death. Long-term follow-up is necessary for detection of endoleak, recurrence, or propagation of the aneurysm, and persistent bacterial infections.

Topics: Adult; Aneurysm, Infected; Anti-Bacterial Agents; Aortic Aneurysm, Thoracic; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Emergencies; Endovascular Procedures; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Prosthesis Design; Rifampin; Staphylococcal Infections; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

High-level methicillin-resistant Staphylococcus aureus (MRSA) isolates show rapid evolution of rifampicin resistance, forcing reliance upon expensive and often inferior antibiotics to manage these infections. Accordingly, this study was conducted to: 1) evaluate the level of multidrug resistance among hospital-associated MRSA isolates from Chennai, India; 2) determine their rifampicin resistance and molecular characterization; and 3) analyze the identified rpoB gene mutations for predominant high-level rifampicin resistance-associated nucleotide changes. Conventional laboratory techniques and antibiogram evaluation by disc diffusion were utilized for isolate phenotypic identification. Among the 54 isolates obtained, 74% (42) were found to be MRSA. All the isolates exhibited complete susceptibility to linezolid and vancomycin, and variable resistance to conventional antibiotics; the MAR index value calculated was 0.64. Genotypic identification of the high-level rifampicin-resistant isolate S. aureus KM05 was established through rpoB amplification and sequencing. The evolutionary relationship of KM05 to other isolates and its rpoB gene mutation status was determined to understand the genetic basis of its high rifampicin resistance. The S. aureus KM05 rpoB gene yielded ≥ 98% sequence similarity and a close phylogenetic relationship with other known reference database organisms. It also showed mutational changes in three rpoB codon positions encoding amino acids at positions 455, 481, and 529. These results have established the prevalence of rifampicin resistance among Chennai hospital MRSA isolates, and suggest that the predominant high-level resistance nucleotide changes would serve to form a basis for their diagnosis and control of rifampicin-resistant MRSA.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genotype; Humans; India; Methicillin-Resistant Staphylococcus aureus; Molecular Sequence Data; Mutation; Phylogeny; Rifampin; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Staphylococcal Infections; Vancomycin

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection.. Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality.. Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up.. Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ciprofloxacin; Cloxacillin; Drug Therapy, Combination; Female; Finland; Humans; Male; Methicillin; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Rifampin; Secondary Prevention; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis; Time-to-Treatment; Treatment Outcome

We hypothesized that systemic ceftriaxone and high concentration local antibiotics might eradicate peri-implant sepsis. Experiment 1: Eighty-four implants inoculated with biofilm-forming Staphylococcus aureus were treated in vitro with gentamicin, vancomycin, gentamicin + rifampin, or vancomycin + rifampin for 2, 4, or 8 days. Experiment 2: Forty-five implants were wired in vivo to rat femurs and inoculated with 1 × 10(6) CFU S. aureus. After 48 h, rats were treated once daily for 5 days with systemic ceftriaxone, local tobramycin or ceftriaxone, and tobramycin. Experiment 3: Forty implants with established S. aureus biofilms were wired in vivo to rat femurs. After 48 h, rats were treated with systemic ceftriaxone alone or in combination with local gentamicin, gentamicin and rifampin, or vancomycin. Experiment 1: 100% of implants treated in vitro with gentamicin were sterile after 48 h. The other treatments did not become sterile until 4 days. Experiment 2: No implant was culture negative. The combination of systemic ceftriaxone and local tobramycin was significantly better than others (p < 0.008). Experiment 3: Systemic ceftriaxone alone was ineffective. All implants treated with systemic ceftriaxone and local gentamicin were sterile (p < 0.001), the other groups were less effective.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Ceftriaxone; Female; Femur; Gentamicins; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Rifampin; Sepsis; Staphylococcal Infections; Stem Cells; Time Factors; Tobramycin; Vancomycin

Staphylococcus haemolyticus is of increasing concern as a cause of several biofilm-associated infections, and today, it represents the second most common organism among clinical isolates of coagulase-negative staphylococci. However, little is known regarding the treatment of infections caused by these bacteria. In this study, we characterize the biofilm formed by S. haemolyticus strains isolated from bloodstream infections and assess in vitro the activity of rifampicin combined with daptomycin or tigecycline against bacteria growing in a biofilm. The results of our studies indicated that the majority (78 %) of methicillin-resistant Staphylococcus haemolyticus strains have the ability to form a biofilm in vitro. None of these strains carried icaADBC genes indicating that they form biofilm via ica-independent mechanisms. The molecular characterization of the biofilm showed that proteins are the predominant matrix component and play a major role in biofilm structure. Extracellular DNA and polysaccharides, other than polysaccharide intercellular adhesin, are also present in the biofilm matrix, but they play a minor role. The images obtained by confocal laser scanning microscopy showed that most S. haemolyticus strains formed a dense biofilm with a low number of dead cells. In vitro study demonstrated excellent activity of tigecycline in combination with rifampicin against cell growth in the proteinous biofilm. The BIC (biofilm inhibitory concentration) value for tigecycline/rifampicin ranged from 0.062 to 1 µg/ml, whereas for daptomycin/rifampicin from 0.125 to 2 µg/ml. These results indicated that the tigecycline/rifampicin combination was more effective against ica-independent biofilm, formed by S. haemolyticus strains, than the daptomycin/rifampicin combination.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus haemolyticus; Tigecycline

Bacterial infection of subcutaneous "pockets" housing cardiovascular implantable electronic devices is a significant clinical complication. In this study, pacemakers encapsulated in a blood plasma-based material (PBM) composited with antibiotics were investigated for use as prophylactics against such infections. PBMs, which are made from pooled allogeneic plasma and platelets, are off-the-shelf biomaterials that can be manufactured in the form of complex 3D shapes, extrudable putties, or injectable pastes. In vitro studies with PBM pastes formulated with rifampicin and minocycline demonstrated antibiotic release over 6 days, activity against Escherichia coli, and reduced cytotoxic effects of the antibiotics on fibroblasts. The materials were also evaluated in vivo in a rabbit model in which pacemaker pockets were inoculated with methicillin-resistant Staphylococcus aureus (S. aureus) strain and examined 1 week later. The pockets containing the pacemaker plus S. aureus were grossly purulent and culture positive, whereas pockets into which PBM with antibiotics were injected around the pacemaker were free of purulence and culture negative (p < 0.001). None of the pockets into which PBM without antibiotics were placed demonstrated purulence, but 60% were culture positive. These results demonstrate the potential of PBMs to deliver antibiotics to diminish the incidence of pocket infections for pacemakers and other implantable devices.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Escherichia coli; Escherichia coli Infections; Methicillin-Resistant Staphylococcus aureus; Minocycline; Pacemaker, Artificial; Plasma; Prostheses and Implants; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone in vitro or in vivo demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P = 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P = 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Foreign Bodies; Male; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections

Staphylococcus pseudintermedius is an opportunistic pathogen recognized as the leading cause of skin, ear, and post-operative bacterial infections in dogs and cats. Zoonotic infections have also recently been reported causing endocarditis, infection of surgical wounds, rhinosinusitis, and catheter-related bacteremia. The aim of the present study is to evaluate, for the first time, the pathogenic potential of S. pseudintermedius isolated from a human infection. To this end, strain DSM 25713, which was recently isolated from a wound of a leukemic patient who underwent a bone marrow transplantation, was investigated for biofilm formation and antibiotic-resistance under conditions relevant for wound infection.. The effect of pH (5.5, 7.1, and 8.7) and the presence of serum (diluted at 1:2, 1:10, and 1:100) on biofilm formation was assessed through a crystal violet assay. The presence of serum significantly reduced the ability to form biofilm, regardless of the pH value tested. In vitro activity of eight antibiotics against biofilm formation and mature 48 h-old biofilms was comparatively assessed by crystal violet assay and viable cell count, respectively. Antibiotics at sub-inhibitory concentrations reduced biofilm formation in a dose-dependent manner, although cefoxitin was the most active, causing a significant reduction already at 1/8xMIC. Rifampicin showed the highest activity against preformed biofilms (MBEC90: 2xMIC). None of the antibiotics completely eradicated the preformed biofilms, regardless of tested concentrations. Confocal and electron microscopy analyses of mature biofilm revealed a complex "mushroom-like" architecture consisting of microcolonies embedded in a fibrillar extracellular matrix.. For the first time, our results show that human wound-associated S. pseudintermedius is able to form inherently antibiotic-resistant biofilms, suggestive of its pathogenic potential, and consistent with recent reports of zoonotic infections.

Topics: Anti-Bacterial Agents; Biofilms; Cefoxitin; Drug Resistance, Multiple, Bacterial; Humans; Hydrogen-Ion Concentration; Rifampin; Staphylococcal Infections; Staphylococcus; Surgical Wound Infection

Whilst levofloxacin (LVX) in combination with rifampicin (RIF) is considered the optimal treatment for prosthetic joint infection (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA), no therapeutic alternatives have been accurately evaluated. Based on the high effectiveness of the combination of daptomycin (DAP) plus RIF against meticillin-resistant S. aureus (MRSA) in this setting, in this study the efficacy of DAP+RIF and DAP+LVX combinations was tested as alternative therapies for foreign-body infections (FBIs) caused by MSSA. A tissue-cage infection model was performed using an MSSA strain. Male Wistar rats were treated for 7 days with LVX, DAP, RIF or the combinations LVX+RIF, DAP+RIF and DAP+LVX. Antibiotic efficacy was evaluated by bacterial counts from tissue cage fluid (TCF) and the cure rate was determined from adhered bacteria. Resistance was screened. Monotherapies were less effective than combinations (P<0.05), and resistance to DAP and RIF emerged. DAP+RIF (decrease in bacterial counts in TCF, -4.9logCFU/mL; cure rate, 92%) was the most effective therapy (P<0.05). There were no differences between LVX+RIF (-3.4logCFU/mL; 11%) and DAP+LVX (-3.3logCFU/mL; 47%). No resistant strains appeared with combined therapies. In conclusion, the combinations DAP+RIF and DAP+LVX showed good efficacy and prevented resistance. DAP+RIF provided higher efficacy than LVX+RIF. These DAP combinations were efficacious alternatives therapies for MSSA FBI. Further studies should confirm whether DAP+RIF may be useful as a first-line therapy in the setting of PJI caused by MSSA.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Complementary Therapies; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Foreign Bodies; Levofloxacin; Male; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Staphylococcus pseudintermedius is a commensal organism of companion animals that is a significant source of opportunistic infections in dogs. With the emergence of clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown to possess potent antibacterial activity against multidrug-resistant strains of Staphylococcus aureus of human and animal concern. Given the genetic similarity between S. aureus and S. pseudintermedius, this study explores the potential use of thiazole compounds as novel antibacterial agents against methicillin-sensitive S. pseudintermedius (MSSP) and MRSP. A broth microdilution assay confirmed these compounds exhibit potent bactericidal activity (at sub-microgram/mL concentrations) against both MSSA and MRSP clinical isolates while the MTS assay confirmed three compounds (at 10 μg/mL) were not toxic to mammalian cells. A time-kill assay revealed two derivatives rapidly kill MRSP within two hours. However, this rapid bactericidal activity was not due to disruption of the bacterial cell membrane indicating an alternative mechanism of action for these compounds against MRSP. A multi-step resistance selection analysis revealed compounds 4 and 5 exhibited a modest (two-fold) shift in activity over ten passages. Furthermore, all six compounds (at a subinihibitory concentration) demonstrated the ability to re-sensitize MRSP to oxacillin, indicating these compounds have potential use for extending the therapeutic utility of β-lactam antibiotics against MRSP. Metabolic stability analysis with dog liver microsomes revealed compound 3 exhibited an improved physicochemical profile compared to the lead compound. In addition to this, all six thiazole compounds possessed a long post-antibiotic effect (at least 8 hours) against MRSP. Collectively the present study demonstrates these synthetic thiazole compounds possess potent antibacterial activity against both MSSP and MRSP and warrant further investigation into their use as novel antimicrobial agents.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Cell Survival; Dog Diseases; Dogs; Lysostaphin; Methicillin; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus; Thiazoles; Vancomycin

This case report describes the treatment of a rare infection caused by Staphylococcus lugdunensis with cefazolin and rifampin.. A 48-year-old man with significant comorbidities was admitted to our institution with complaints of malaise, shortness of breath, and vague persistent pain. He was diagnosed with S. lugdunensis infective endocarditis and was treated with cefazolin continuous infusion for 10 days without resolution of bacteremia. As surgical intervention was deemed inappropriate, rifampin was added to the treatment regimen for its antibiofilm activity. After rifampin initiation, resolution of bacteremia was rapidly achieved. Subsequent blood cultures remained negative, and the patient was discharged home in stable condition to complete six weeks of i.v. cefazolin and rifampin therapy. The patient continued treatment, as documented by the infusion center, weekly for five weeks. The patient was rehospitalized during his sixth week of treatment due to impending respiratory failure, whereupon he was intubated and admitted to the intensive care unit. The patient's cardiac status gradually worsened over the following days, and he ultimately died. Blood cultures from days 1 and 2 of hospitalization revealed no bacterial growth at five days.. Cefazolin and rifampin therapy in a hospitalized patient with bacteremia and aortic valve endocarditis caused by S. lugdunensis resulted in rapid eradication of the bacteremia. After more than five weeks of cefazolin-rifampin treatment, the patient was rehospitalized with worsening cardiac function and died. Blood cultures during the second admission were negative.

Topics: Anti-Bacterial Agents; Bacteremia; Cefazolin; Drug Therapy, Combination; Endocarditis, Bacterial; Fatal Outcome; Humans; Infusions, Intravenous; Liver Function Tests; Male; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis

The purpose of this study was to investigate the curative effect of bone-like hydroxyapatite/poly amino acid (BHA/PAA) as a carrier for poly(lactic-co-glycolic acid)-coated rifapentine microsphere (RPM) in the treatment of rabbit chronic osteomyelitis induced by Staphylococcus aureus.. RPM was prepared through an oil-in-water emulsion solvent evaporation method, and RPM was combined with BHA/PAA to obtain drug-loaded, slow-releasing materials. Twenty-six New Zealand white rabbits were induced to establish the animal model of chronic osteomyelitis. After debridement, the animals were randomly divided into three groups (n=8): the experimental group (with RPM-loaded BHA/PAA), the control group (with BHA/PAA), and the blank group. The RPM-loaded BHA/PAA was evaluated for antibacterial activity, dynamics of drug release, and osteogenic ability through in vitro and in vivo experiments.. In vitro, RPM-loaded BHA/PAA released the antibiotics slowly, inhibiting the bacterial growth of S. aureus for up to 5 weeks. In vivo, at week 4, the bacterial colony count was significantly lower in the experimental group than in the control and blank groups (P<0.01). At week 12, the chronic osteomyelitis was cured and the bone defect was repaired in the experimental group, whereas the infection and bone defect persisted in the control and blank groups.. In vitro and in vivo experiments demonstrated that RPM-loaded BHA/PAA effectively cured S. aureus-induced chronic osteomyelitis. Therefore, BHA/PAA has potential value as a slow-releasing material in clinical setting. Further investigation is needed to determine the optimal dosage for loading rifapentine.

Topics: Amino Acids; Animals; Anti-Bacterial Agents; Chronic Disease; Delayed-Action Preparations; Drug Carriers; Durapatite; Lactic Acid; Microspheres; Osteomyelitis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Abscess; Adolescent; Allografts; Aorta; Aortic Rupture; Aortic Valve; Aortic Valve Insufficiency; Bicuspid Aortic Valve Disease; Cardiac Surgical Procedures; Chest Pain; Drug Resistance, Bacterial; Dyspnea; Endocarditis; Gentamicins; Heart Murmurs; Heart Valve Diseases; Humans; Male; Nafcillin; Pericardial Effusion; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis; Vancomycin; Vascular Grafting

Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Coagulase; Drug Resistance, Multiple, Bacterial; France; Fusidic Acid; Gentamicins; Hospitals; Humans; Levofloxacin; Linezolid; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prospective Studies; Rifampin; RNA, Ribosomal, 23S; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staphylococcal Infections; Staphylococcus epidermidis

In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.

Topics: Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Clindamycin; Cross Infection; Doxycycline; Drug Resistance, Multiple, Bacterial; Fusidic Acid; Humans; Joint Prosthesis; Linezolid; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues were synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and screened for their in vitro anti-tubercular and antibacterial activity. Many of these compounds exhibited MIC values in the range 7.32-136.10 μM against Mycobacterium tuberculosis H37Rv. Eight compounds were further subjected to cytotoxic studies. Furthermore, the title compounds were screened for antibacterial activity against Staphylococcus aureus ATCC 29213 (gram positive) and Escherichia coli ATCC 25922 (gram negative) bacteria. Many of these compounds exhibited MIC values in the range 0.44-34.02 μM. Compound 3f was found to be the most active with an MIC of 0.44 and 0.8 μM respectively against both the strains. In general, the antibacterial activity of title compounds was more prominent.

Topics: Anti-Bacterial Agents; Carboxylic Acids; Escherichia coli; Escherichia coli Infections; Halogenation; Humans; Mycobacterium tuberculosis; Quinolines; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship; Tuberculosis

Prolonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960; P = 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P = 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P = 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Arthritis, Infectious; Bone and Bones; Discitis; Female; Fluoroquinolones; Humans; Hypokalemia; Inflammation; Jaundice, Obstructive; Joints; Male; Middle Aged; Osteomyelitis; Penicillins; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

Acute ethmoiditis is a rare infection of ethmoidal cells. The pathognomonic sign is an edema of the internal corner of the eye. Imaging may be necessary to verify the absence of orbital or endocranial complications. Thrombophlebitis of the cavernous sinus is a serious complication of this infectious process. We report the case of an 11-year-old boy who presented with ethmoiditis complicated with thrombophlebitis of the cavernous sinus, with right hemiplegia and left Bell palsy sequelae. Early diagnosis of this disorder and urgent therapy are essential. Treatment is based on the antibiotic therapy.

Topics: Acute Disease; Cavernous Sinus; Cavernous Sinus Thrombosis; Combined Modality Therapy; Drug Therapy, Combination; Early Diagnosis; Ethmoid Sinus; Ethmoid Sinusitis; Facial Paralysis; Hemiplegia; Humans; Magnetic Resonance Imaging; Methicillin-Resistant Staphylococcus aureus; Physical Therapy Modalities; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Vancomycin

The prevalence of resistance to rifampicin and fusidic acid among Malaysian strains of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. This study aimed to determine the mechanisms of rifampicin and fusidic acid resistance and the genetic diversity of MRSA strains from a Malaysian tertiary hospital.. Minimum inhibitory concentrations (MIC) for 21 MRSA strains were determined by agar dilution test and Etest. The resistance genes, staphylococcal chromosome cassette mec (SCCmec) types, multilocus-sequence typing (MLST) types and spa types, were determined by PCR and DNA sequencing.. MIC for rifampicin and fusidic acid resistance ranged from <1 to 8 µg/ml and from <1 to 256 µg/ml, respectively. A double mutation (484Arg/His and 517Glu/Gln) in rpoB causes high rifampicin resistance while a mutational change (461Leu/Lys) in fusA was observed in seven strains highly resistant to fusidic acid. Five of the seven were also resistant to rifampicin (MIC 8 µg/ml) and carried a mutated rpoB gene (484Arg/His). No other acquired fusidic acid resistance gene (fusB, fusC or fusD) was detected. Most (14/21) of the strains belonged to clone ST239-III-t037. Three belonged to ST22-IV-t1378 and the remaining four to ST239-III-t2029, ST239-III-t421, ST1178-IV-t1107 and ST241-III-t363, respectively.. The study showed that both rifampicin and fusidic acid resistance was associated with mutational change in rpoB and fusA, respectively. All rifampicin-resistant strains were from the same clone ST239-III-t037 whereas strains resistant to fusidic acid were genetically more diverse.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Fusidic Acid; Malaysia; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Peptide Elongation Factor G; Rifampin; Staphylococcal Infections

Staphylococcus epidermidis is a commensal inhabitant of the healthy human skin, but in the recent years, it has been recognized as a nosocomial pathogen especially in immunocompromised patients. The pathogenesis of S. epidermidis is thought to be based on its capacity to form biofilms on the surface of medical devices, where bacterial cells may persist, protected from host defence and antimicrobial agents. Rifampin has been shown to be one of the most active antimicrobial agents in the eradication of the staphylococcal biofilm. However, this antibiotic should not be used in monotherapy. Therefore, one of the objectives of our research was to study the efficacy of the tigecycline/rifampin combination against methicillin-resistant S. epidermidis embedded in biofilms. Of the 80 clinically significant S. epidermidis isolates, 75 strains possess the ability to form a biofilm. These bacteria formed the biofilm via ica-dependent mechanisms. However, other biofilm-associated genes, including aap (encoding accumulation-associated protein) and bhp (coding cell wall-associated protein), were present in 85 and 29 % of isolates, respectively. The biofilm structures of S. epidermidis strains were also analyzed in confocal laser scanning microscopy (CLSM) and the obtained image demonstrated differences in their architecture. In vitro studies showed that the MIC value for tigecycline against S. epidermidis growing in the biofilm ranged from 0.125 to 2 μg/mL. Tigecycline in combination with rifampin demonstrated higher activity against bacteria embedded in biofilms than tigecycline alone.

Topics: Anti-Infective Agents; Biofilms; DNA, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Microscopy, Confocal; Minocycline; Polymerase Chain Reaction; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline

Topics: Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Arthritis, Infectious; Arthroplasty, Replacement; Humans; Postoperative Care; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections

The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.

Topics: Animals; Anti-Bacterial Agents; Cefazolin; Male; Mice; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 μg/ml; daptomycin, 0.125 μg/ml; vancomycin, 1 μg/ml; rifampin, 0.04 μg/ml; and tigecycline, 0.125 μg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log10 CFU/ml at 128 × the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by <1 log10 CFU/ml with fosfomycin and tigecycline, 1.7 log10 with daptomycin, 2.2 log10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log10 with fosfomycin-daptomycin, and >6.0 log10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cage-associated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 μg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cage-associated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-associated infections, but it cannot replace rifampin as an antibiofilm agent.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Fosfomycin; Guinea Pigs; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

Coagulase-negative Staphylococci, including Staphylococcus epidermidis, are common pathogens in orthopedic prosthesis infections. Operation and prolonged treatment with rifampicin in combination with another antibiotic is often required. Coagulase-negative Staph-ylococci are frequently multi-resistant, but resistance to vancomycin is rare in Sweden. Linezolid is an alternative, however it is only recommended for up to 4 weeks treatment due to risk of hematological side effects. We have successfully used prolonged treatment with linezolid and rifampicin in a patient suffering from a complicated prosthetic joint infection caused by a vancomycin resistant Staphyloccous epidermidis strain.

Topics: Acetamides; Anti-Bacterial Agents; Humans; Knee Prosthesis; Linezolid; Male; Middle Aged; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Outcome; Vancomycin; Vancomycin Resistance

Orthopaedic implants are highly susceptible to infection. The aims of treatment of infection associated with internal fixation devices are fracture consolidation and prevention of chronic osteomyelitis. Complete biofilm eradication is not the primary goal, as remaining adherent microorganisms can be removed with the device after fracture consolidation. By contrast, in periprosthetic joint infection (PJI), biofilm elimination is required. Surgical treatment of PJI includes debridement with retention, one- or two-stage exchange and removal without reimplantation. In addition, prolonged antibiotic treatment, preferably with an agent that is effective against biofilm bacteria, is required. Rifampicin is an example of an antibiotic with these properties against staphylococci. However, to avoid the emergence of resistance, rifampicin must always be combined with another antimicrobial agent. With this novel treatment approach, orthopaedic implant-associated infection is likely to be eradicated in up to 80-90% of patients. Because most antibiotics have a limited effect against biofilm infections, novel prophylactic and therapeutic options are needed. Surface coating with antimicrobial peptides that reduce bacterial attachment and biofilm formation can potentially prevent implant-associated infection. In addition, quorum-sensing inhibitors are a novel therapeutic option against biofilm infections.

Topics: Anti-Bacterial Agents; Coated Materials, Biocompatible; Debridement; Fractures, Bone; Humans; Internal Fixators; Male; Middle Aged; Osteomyelitis; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

There exists considerable debate concerning management of prosthetic vascular graft infection (PVGI), especially in terms of antimicrobial treatment. This report studies factors associated with treatment failure in a cohort of patients with staphylococcal PVGI, along with the impact of rifampin (RIF).. All data on patients with PVGI between 2006 and 2010 were reviewed. Cure was defined as the absence of evidence of infection during the entire post-treatment follow-up for a minimum of one year. Failure was defined as any other outcome.. 84 patients (72 M/12 F, median age 64.5 ± 11 y) with diabetes mellitus (n = 25), obesity (n = 48), coronary artery disease (n = 48), renal failure (n = 24) or COPD (n = 22) were treated for PVGI (median follow-up was 470 ± 469 d). PVGI was primarily intracavitary (n = 47). Staphylococcus aureus (n = 65; including 17 methicillin-resistant S. aureus) and coagulase-negative Staphylocococcus (n = 22) were identified. Surgical treatment was performed in 71 patients. In univariate analysis, significant risk factors associated with failure were renal failure (p = 0.04), aortic aneurysm (p = 0.03), fever (p = 0.009), aneurysm disruption (p = 0.02), septic shock in the peri-operative period (p = 0.005) and antibiotic treatment containing RIF (p = 0.03). In multivariate analysis, 2 variables were independently associated with failure:septic shock [OR 4.98: CI 95% 1.45-16.99; p=0.01] and antibiotic containing rifampin [OR: 0.32: CI95% 0.10-0.96; p=0.04].. Results of the present study suggest that fever, septic shock and non-use of antibiotic treatment containing RIF are associated with poor outcome.

Topics: Aged; Anti-Bacterial Agents; Blood Vessel Prosthesis Implantation; Cohort Studies; Female; France; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Multivariate Analysis; Prospective Studies; Prosthesis-Related Infections; Rifampin; Risk Factors; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Rifampin; Rifamycins; Rifaximin; Staphylococcal Infections

The aim of this study was to determine the prevalence, SCCmec types, presence of the Panton-Valentine leukocidin (PVL) gene, and susceptibility to antibiotics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from hospitalized children.. From August 2009 to September 2011, 291 S. aureus strains were isolated from normally sterile body sites, of which 190 (65%) were MRSA. One hundred and two of the MRSA strains were genetically evaluated. SCCmec genotypes were identified by M-PCR and the PVL gene (pvl) by end-point PCR. Resistance to erythromycin, rifampicin, clindamycin, and trimethoprim-sulfamethoxazole (SXT) was assessed by Kirby-Bauer disk diffusion method in accordance with the Clinical and Laboratory Standards Institute guidelines of 2012.. Of the 102 strains evaluated, 97 (95%) were SCCmec type II, 5 (5%) were SCCmec type IVa, and all (100%) were pvl-negative. Resistance to erythromycin, clindamycin, rifampicin, and SXT was 97%, 95%, 0%, and 0%, respectively.. The prevalence of hospital-acquired MRSA was high. SCCmec type II was predominant and the pvl gene appeared not to play any role in the virulence of the MRSA strains from hospitalized children.

Topics: Anti-Bacterial Agents; Child; Clindamycin; Cross Infection; Disk Diffusion Antimicrobial Tests; Erythromycin; Genes, Bacterial; Hospitalization; Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Mexico; Molecular Typing; Prevalence; Rifampin; Staphylococcal Infections; Tertiary Healthcare; Trimethoprim, Sulfamethoxazole Drug Combination

New strategies to decrease infection rates in cementless arthroplasty are needed, especially in the context of the growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections. The purpose of this study was to investigate the antimicrobial activity of a rifampicin-fosfomycin coating against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA in a rabbit infection prophylaxis model. Uncoated or rifampicin-fosfomycin-coated K-wires were inserted into the intramedullary canal of the tibia in rabbits and contaminated with an inoculation dose of 10(5) or 10(6) colony-forming units of MSSA EDCC 5055 in study 1 and MRSA T6625930 in study 2, respectively. After 28days the animals were killed and clinical, histological and microbiological assessment, including pulse-field gel electrophoresis, was conducted. Positive culture growth in agar plate testing and/or clinical signs and/or histological signs were defined positive for infection. Statistical evaluation was performed using Fisher's exact test. Both studies showed a statistically significant reduction of infection rates for rifampicin-fosfomycin-coated implants compared to uncoated K-wires (P=0.015). In both studies none of the 12 animals that were treated with a rifampicin-fosfomycin-coated implant showed clinical signs of infection or a positive agar plate testing result. In both studies, one animal of the coating group showed the presence of sporadic bacteria with concomitant inflammatory signs in histology. The control groups in both studies exhibited an infection rate of 100% with clear clinical signs of infection and positive culture growth in all animals. In summary, the rifampicin-fosfomycin-coating showed excellent antimicrobial activity against both MSSA and MRSA, and therefore warrants further clinical testing.

Topics: Animals; Antibiotics, Antitubercular; Bone Wires; Coated Materials, Biocompatible; Fosfomycin; Materials Testing; Methicillin-Resistant Staphylococcus aureus; Prostheses and Implants; Rabbits; Rifampin; Staphylococcal Infections

We compared the efficacies of daptomycin (doses equivalent to 8 to 10 mg/kg of body weight/day in humans) and cloxacillin alone with those of cloxacillin-rifampin and cloxacillin-daptomycin combinations, using a tissue cage methicillin-susceptible Staphylococcus aureus (MSSA) infection model. Monotherapies were less effective than combinations (P<0.05), and daptomycin resistance emerged. Cloxacillin-daptomycin proved as effective as cloxacillin-rifampin and prevented the appearance of resistance; this combination may be an alternative anti-MSSA therapy, which may offer greater benefits in the early treatment of prosthetic joint infections (PJI).

Topics: Animals; Anti-Bacterial Agents; Cloxacillin; Daptomycin; Drug Combinations; Microbial Sensitivity Tests; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To evaluate in vitro and in vivo efficacies of linezolid, vancomycin, and the combination of linezolid and rifampicin against two Staphylococcus aureus strains with reduced susceptibility to beta-lactams and one of them also to glycopeptides.. In vitro killing curves and a rabbit model: Meningitis was induced by intracisternal inoculation of 10(8) CFU/ml of each strain. Five hours later (0 h), rabbits were randomly assigned to control or to therapeutic groups. CSF bacterial counts, lactate and protein concentrations, and pharmacokinetic parameters were determined.. In vivo: linezolid and its combination with rifampicin reduced bacterial concentrations at 24 h, median cfu/mL 4.85 vs 3.87 (p < 0.05) for linezolid and 5.02 vs 4.21 (p < 0.05) for linezolid + rifampicin, against the glycopeptide intermediate S. aureus (GISA) strain and improved inflammatory parameters.. Despite the need for more experimental data, our results suggest that linezolid and its combinations could be considered as a potential alternative in difficult-to-treat CNS infections and especially in those due to GISA strains and deserve more studies.

Topics: Acetamides; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Glycopeptides; Linezolid; Meningitis, Bacterial; Microbial Sensitivity Tests; Oxazolidinones; Rabbits; Random Allocation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10 + R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010-2012) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: 2 (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58-90). Clinical failure was observed in 9 (50%) patients: in 5 cases, staphylococci were recovered (28% of microbiological failures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rate was similar, but whereas in the historical series, failure occurred fundamentally during therapy, in the present series, it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Sequence type 72 methicillin-resistant Staphylococcus aureus (MRSA) SCCmec type IV (ST72-MRSA-IV) is the most common community-acquired MRSA clone in Korea. Resistance to daptomycin or vancomycin among community-acquired MRSA clones is not well described in the literature. We herein report the first case of vancomycin-intermediate, daptomycin-nonsusceptible ST72-MRSA-IV.. A 45-year-old Japanese man underwent aortic arch prosthesis implantation for treatment of a dissecting aortic aneurysm. Fourteen months later, he developed a prosthetic graft infection of the aortic arch and an anterior mediastinal abscess caused by ST72-MRSA-IV. First-line treatment with vancomycin and rifampicin failed, and daptomycin was thus administered. After several days, the treatment was changed to linezolid because of the re-emergence of fever. The patient's condition resolved and no recurrence or other problems were seen for 1 year post-treatment. The infectious agent was definitively identified as vancomycin-intermediate, daptomycin-nonsusceptible, rifampicin-resistant ST72-MRSA-IV based on culture results and minimum inhibitory concentration testing.. This case report illustrates the importance of fully understanding the changing epidemiology of infectious agents and the risk factors for the development of antibiotic resistance. Such information will help to minimize the emergence and spread of antibiotic-resistant strains. This report concerns one particular bacterial strain; however, the basic concepts involved in this case translate to all infectious disease fields.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Vancomycin

A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [(18)F]fluoro-deoxyglucose-MicroPET ([(18)F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [(18)F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [(18)F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Catheters, Indwelling; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Mice; Microbial Sensitivity Tests; Positron-Emission Tomography; Radiopharmaceuticals; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Staphylococcal biofilms are a major concern in both clinical and food settings because they are an important source of contamination. The efficacy of established cleaning procedures is often hindered due to the ability of some antimicrobial compounds to induce biofilm formation, and to the presence of persister cells, a small bacterial subpopulation that exhibits multidrug tolerance. Phage lytic enzymes have demonstrated antimicrobial activity against planktonic and sessile bacteria. However, their ability to lyse and/or select persister cells remains largely unexplored so far. In this work, the lytic activity of the endolysin LysH5 against Staphylococcus aureus and Staphylococcus epidermidis biofilms was confirmed. LysH5 reduced staphylococcal sessile cell counts by 1-3 log units, compared with the untreated control, and sub-inhibitory concentrations of this protein did not induce biofilm formation. LysH5-surviving cells were not resistant to the lytic activity of this protein, suggesting that no persister cells were selected. Moreover, to prove the lytic ability of LysH5 against this subpopulation, both S. aureus exponential cultures and persister cells obtained after treatment with rifampicin and ciprofloxacin were subsequently treated with LysH5. The results demonstrated that besides the notable activity of endolysin LysH5 against staphylococcal biofilms, persister cells were also inhibited, which raises new opportunities as an adjuvant for some antibiotics.

Topics: Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Endopeptidases; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus Phages

We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate.

Topics: Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacteremia; Daptomycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Central venous catheters (CVC) removal and reinsertion of a new CVC in the setting of central line associated bloodstream infections (CLABSI) is not always possible in septic patients. The purpose of this study was to evaluate the outcome of patients with Staphylococcus aureus-CLABSI (SA-CLABSI) who had their CVCs exchanged over guidewire for minocycline/rifampin-coated (M/R)-CVC within seven days of bacteremia.. Each case was matched with two control patients who had SA-CLABSI and had their CVC removed within seven days and two control patients who had their CVC retained beyond seven days. In addition, an in vitro model was developed for exchange of catheters.. We identified 40 patients with SA-CLABSI. Eight patients had their CVC exchanged over guidewire with M/R-CVC and were compared to 16 patients who had their CVC removed and 16 other patients who had their CVC retained. Patients who had their CVC exchanged over guidewire had a similar clinical response and relapse rates compared to patients whose CVC was removed or retained. However the rate of overall mortality was higher in patients who retained their CVC compared to those whose CVC was exchanged or removed (p = 0.034). The in vitro catheter exchange model showed that catheter exchange over guidewire using M/R-CVC completely prevented biofilm colonization compared to exchange using uncoated CVC (p < 0.0001).. In the setting of SA-CLABSI, exchanging the CVC over guidewire with M/R-CVC could be an alternative to removing the CVC and reinserting another CVC at a different site and may be associated with a lower rate of overall mortality. Further large prospective randomized clinical trials are warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Minocycline; Recurrence; Retrospective Studies; Rifampin; Staphylococcal Infections; Young Adult

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Chest Pain; Confusion; Cough; Diagnosis, Differential; Dyspnea; Dysuria; Female; Floxacillin; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Risk Factors; Staphylococcal Infections; Treatment Outcome

Septic cavernous sinus thrombosis is a rare clinical condition. Although Staphylococcus aureus is the most common pathogen causing septic cavernous sinus thrombosis [CST], it is an uncommon cause of meningitis. We report the first case of CST with meningitis in Hyderabad, Andhra Pradesh, caused by community acquired epidemic strain of Methicillin resistant staphylococcus aureus [MRSA], in a previously healthy individual with no risk factors. The patient recovered completely following treatment with Vancomycin. We consecutively reviewed all cases of community acquired staphylococcus aureus [CA-MRSA] with central nervous system involvement available in literature.

Topics: Adolescent; Basal Ganglia Cerebrovascular Disease; Brain; Cavernous Sinus Thrombosis; Cerebral Infarction; Community-Acquired Infections; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Meningitis, Bacterial; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Staphylococcus aureus is the main causal pathogen of infective endocarditis (IE), which may have distinct origins, namely, community, nosocomial, or non-nosocomial healthcare-associated (NNHCA). We report the first case of NNHCA-IE caused by methicillin-resistant S. aureus strain USA400/SCCmec IV in which the combination therapy of rifampin and vancomycin had a favorable outcome for the patient.

Topics: Adult; Anti-Bacterial Agents; Brazil; Echocardiography, Transesophageal; Endocarditis; Genotype; Health Facilities; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Molecular Typing; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Meticillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen of humans and many animal species, and has become established as a veterinary pathogen.. In this case report we describe an MRSA infection in a dwarf rabbit, treatment of the infection and, subsequently, the genetic analysis of the isolated strain. The pet rabbit was presented to an animal hospital due to recurrent swellings on the head and on the neck. Bacteriological examination yielded Staphylococcus aureus, which was resistant to β-lactam antibiotics. The isolate was confirmed as an MRSA by mecA PCR, Panton-Valentine leukocidin (PVL) negative, and typed as multilocus sequence type (ST)398/staphylococcal protein A (spa) type t011/staphylococcal cassette chromosome mec (SCCmec) type SCCmecIVa. The rabbit was treated with rifampicin for 2 weeks. After 2.5 weeks the rabbit was clinically normal and control swabs were negative for MRSA.. This study is the first to report MRSA in a rabbit in Austria. This study contributes to the growing evidence that MRSA ST398 could be isolated from a variety of animals.

Topics: Animals; Anti-Bacterial Agents; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Pets; Rabbits; Rifampin; Staphylococcal Infections

A 67-year-old gentleman developed persistent Staphylococcus epidermidis bacteraemia following transjugular intrahepatic portal shunting. 'Endotipsitis' was diagnosed. Conventional therapy with a vancomycin infusion, amikacin and rifampicin failed after 17 days. He was cured with a 6-week course of high-dose (8 mg/kg) daptomycin monotherapy.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters; Daptomycin; Drug Resistance, Multiple, Bacterial; Humans; Male; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Failure; Vancomycin

We report the findings of a study examining the relationship between in vitro daptomycin-rifampin synergy and the therapeutic outcome of 12 patients with complex deep methicillin-resistant Staphylococcus aureus (MRSA) infections treated for prolonged periods with this combination. Checkerboard synergy was found in nine cases and was 100% predictive of therapeutic success; absence of synergy was found in three cases, two of which were therapeutic failures (P = 0.045). No relationship was observed between synergy and outcome by time-kill assessment. Checkerboard synergy may predict clinical response to daptomycin plus rifampin for complex invasive MRSA infections requiring prolonged treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Daptomycin; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Treatment Outcome; Young Adult

Chronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures.. Eleven CF patients, (median age: 9 years (range 1-43); median FEV1: 91%pred (95%CI 74%-100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation.. Chronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Disease Eradication; Female; Forced Expiratory Volume; Humans; Infant; Male; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Nasal Mucosa; Nucleic Acid Synthesis Inhibitors; Ointments; Prospective Studies; Rifampin; Staphylococcal Infections; Young Adult

Received 29 November 2012; returned 20 February 2013; revised 16 May 2013; accepted 18 May 2013 OBJECTIVES: Raised vancomycin MICs have been associated with poor outcomes for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in the USA and mainland Europe. We investigated if this also applies in the UK, where EMRSA-15 (clonal complex 22) dominates.. Isolates from UK patients receiving vancomycin therapy for MRSA bacteraemia in 2008-10 were collected, along with clinical details. Outcomes (i.e. patient survival or bacteraemia resolution) were reported 28 days after vancomycin therapy ended. The relationship between clinical outcome and MIC--as determined by CLSI and BSAC agar dilution methods--was assessed.. Among 228 MRSA bacteraemias, 82% were caused by EMRSA-15; 65% of the patients were male and the median age was 70.5 years. MICs correlated between methods, but CLSI agar dilution testing gave a mode at 1 mg/L with only 12% of results either side, whereas the BSAC method gave a mode straddling 0.7-1 mg/L with <4% outliers. Twenty-three percent of patients died, with MRSA contributory in half; another 17% had unresolved bacteraemia at 28 days. Neither death nor unresolved bacteraemia was significantly associated with higher vancomycin MICs by either method. Rifampicin co-therapy had no quantifiable effect on outcome. The patient's age was the only significant correlate of patient outcome (P < 0.01); the underlying medical condition of the patient was important for the resolution of bacteraemia (P < 0.01), though not for overall mortality.. Subtle vancomycin MIC differences did not correlate with worse outcomes for vancomycin monotherapy or for vancomycin/rifampicin co-therapy in MRSA bacteraemia. Regardless of the exact MIC-outcome relationship, detecting such small MIC differences seems unlikely to be reliable in routine laboratories.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Prognosis; Rifampin; Staphylococcal Infections; Treatment Outcome; United Kingdom; Vancomycin; Young Adult

The activity of dalbavancin, a representative of the lipoglycopeptide antibiotics, alone and in combination with rifampicin, was investigated against meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBC(log)) and stationary (MBC(stat)) growth phases. The pharmacokinetic profile of dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal dalbavancin (40, 60 or 80 mg/kg as a single dose), rifampicin (12.5 mg/kg/12 h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of dalbavancin was 0.078 mg/L; MBC(log) and MBC(stat) were both >128× MIC. In time-kill studies, bacterial reduction of 3log(10)CFU/mL was achieved after 48 h at ≥32× MIC (logarithmic growth) and at ≥1× MIC (stationary growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin, and prevented the emergence of rifampicin resistance in vitro. The half-life of dalbavancin in cage fluid was 35.8-45.4 h and the concentration remained above the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60 mg/kg and 80 mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80 mg/kg cured 36% of infected cages, and emergence of rifampicin resistance was completely prevented. Dalbavancin at 80 mg/kg and in combination with rifampicin eradicated approximately one-third of cage-associated MRSA infections and prevented emergence of rifampicin resistance.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Drug Resistance, Bacterial; Drug Therapy, Combination; Guinea Pigs; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prostheses and Implants; Rifampin; Staphylococcal Infections; Teicoplanin

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Communicable Diseases, Emerging; Community-Acquired Infections; Endocarditis, Bacterial; Female; Gastrectomy; Genes, Bacterial; Gentamicins; Humans; Lymphoma, B-Cell, Marginal Zone; Methicillin-Resistant Staphylococcus aureus; Mitral Valve Insufficiency; Multiple Sclerosis; Neoplasms, Second Primary; Ovarian Neoplasms; Postoperative Complications; Rifampin; Staphylococcal Infections; Stomach Neoplasms; Vancomycin

Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Male; Mice; Mice, Inbred C57BL; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

No mutant-prevention concentration (MPC) with methicillin-resistant Staphylococcus epidermidis (MRSE) has been reported. The study aimed to evaluate the propensity of vancomycin individually and in combination to prevent MRSE from mutation. A total of 10 MRSE clinical isolates were included in the study. Susceptibility testing demonstrated that the susceptibility rates to vancomycin, rifampicin, levofloxacin and fosfomycin were 100, 100, 50 and 90%, respectively. The fractional inhibition concentration indices (FICI) for vancomycin combined with rifampicin, levofloxacin or fosfomycin were ≥1.5 but ≤2, ≥1.5 but ≤2, and >0.5 but ≤1.5, respectively, implying indifferent interactivity. The MPC with susceptible strains was determined to be the lowest antibiotic concentration inhibiting visible growth among 10(10) CFU on four agar plates (9 cm in diameter) after a 72-h incubation at 37°C. The MPCs were 16~32, >64, ≥64 and 4~16 μg ml(-1) for vancomycin, rifampicin, fosfomycin and levofloxacin, respectively. The vancomycin MPCs of combinations with fosfomycin (32 μg ml(-1)), levofloxacin (2 μg ml(-1)) and rifampicin (2 or 4 μg ml(-1)) were 1~4, 16~32 and 16~32 μg ml(-1), respectively. Against mutants selected by vancomycin, rifampicin, levofloxacin and fosfomycin individually, antibiotics had standard MICs of 2~4 μg ml(-1) for vancomycin, >64 μg ml(-1) for rifampicin, 4~8 μg ml(-1) for levofloxacin and 64 μg ml(-1) for fosfomycin. Thus single-step mutation can lead to resistance of MRSE to rifampicin, levofloxacin and fosfomycin, rather than non-susceptibility to vancomycin. Vancomycin-fosfomycin combination might be a superior alternative to vancomycin in blocking the growth of MRSE mutants, especially for high-organism-burden infections.

Topics: Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Genes, Bacterial; Humans; Levofloxacin; Methicillin Resistance; Microbial Sensitivity Tests; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Chronic infections are difficult to treat with antibiotics but are caused primarily by drug-sensitive pathogens. Dormant persister cells that are tolerant to killing by antibiotics are responsible for this apparent paradox. Persisters are phenotypic variants of normal cells and pathways leading to dormancy are redundant, making it challenging to develop anti-persister compounds. Biofilms shield persisters from the immune system, suggesting that an antibiotic for treating a chronic infection should be able to eradicate the infection on its own. We reasoned that a compound capable of corrupting a target in dormant cells will kill persisters. The acyldepsipeptide antibiotic (ADEP4) has been shown to activate the ClpP protease, resulting in death of growing cells. Here we show that ADEP4-activated ClpP becomes a fairly nonspecific protease and kills persisters by degrading over 400 proteins, forcing cells to self-digest. Null mutants of clpP arise with high probability, but combining ADEP4 with rifampicin produced complete eradication of Staphylococcus aureus biofilms in vitro and in a mouse model of a chronic infection. Our findings indicate a general principle for killing dormant cells-activation and corruption of a target, rather than conventional inhibition. Eradication of a biofilm in an animal model by activating a protease suggests a realistic path towards developing therapies to treat chronic infections.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Depsipeptides; Drug Resistance, Bacterial; Enzyme Activation; Female; Mice; Microbial Viability; Proteolysis; Proteomics; Rifampin; Serine Endopeptidases; Staphylococcal Infections; Staphylococcus aureus

As the number of CA-MRSA skin and soft tissue infections continues to grow, it's important to know which patients are at greatest risk and which evidence-based treatment protocols to turn to when needed.

Topics: Acetamides; Administration, Topical; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Continuity of Patient Care; Cross Infection; Ethnicity; Humans; Linezolid; Medical History Taking; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Oxazolidinones; Patient Education as Topic; Physical Examination; Practice Guidelines as Topic; Rifampin; Risk Factors; Secondary Prevention; Skin; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Primary pyomyositis is a rare bacterial infection of the skeletal muscle. Traditionally a tropical disease, it is increasingly described in westernised urban populations. The aetiology is due to transient bacteraemia in the presence of risk factors such as traumatised muscle, or immunocompromise. The condition presents in one of three stages, representing progression of disease severity. Intravenous antibiotic therapy is often sufficient for this disease at its early stage, but surgical drainage is necessary for advanced presentations. We report a severe case of stage 3 pyomyositis of the gluteus minimus, which led to Staphylococcus aureus sepsis, deranged liver function, acute kidney injury, autoanticoagulation and proximal femoral osteomyelitis in a healthy 64-year-old Caucasian man. This illustrates the potential severity of the disease, the life-threatening sequelae when diagnosis is delayed and the role of surgical drainage in averting the progression of systemic sepsis to end-organ dysfunction, disseminated intravascular coagulation and potentially death.

Topics: Anti-Bacterial Agents; Buttocks; Delayed Diagnosis; Drainage; Humans; Male; Middle Aged; Muscle, Skeletal; Osteomyelitis; Pyomyositis; Rifampin; Sepsis; Staphylococcal Infections; Vancomycin

Menstrual toxic shock syndrome (MTSS) is a rare and potentially life-threatening illness. We present a case of recurrent MTSS initially associated with tampon use that continued to recur when tampons were discontinued, which was successfully treated with rifampicin and clindamycin.

Topics: Adolescent; Anti-Bacterial Agents; Carrier State; Clindamycin; Female; Humans; Menstrual Hygiene Products; Recurrence; Rifampin; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus

Several series predicting the prognosis of staphylococcal prosthetic joint infection (PJI) managed with debridement, antibiotics, and implant retention (DAIR) have been published, but some of their conclusions are controversial. At present, little is known regarding the efficacy of the different antibiotics that are used or their ability to eliminate methicillin-resistant S. aureus (MRSA) infection.. This was a retrospective, multicenter, observational study of cases of PJI by S. aureus that were managed with DAIR (2003-2010). Cases were classified as failures when infection persistence/relapse, death, need for salvage therapy, or prosthesis removal occurred. The parameters that predicted failure were analyzed with logistic and Cox regression.. Out of 345 episodes (41% men, 73 years), 81 episodes were caused by MRSA. Fifty-two were hematogenous, with poorer prognoses, and 88% were caused by methicillin-susceptible S. aureus (MSSA). Antibiotics were used for a median of 93 days, with similar use of rifampin-based combinations in MSSA- and MRSA-PJI. Failure occurred in 45% of episodes, often early after debridement. The median survival time was 1257 days. There were no overall prognostic differences between MSSA- and MRSA-PJI, but there was a higher incidence of MRSA-PJI treatment failure during the period of treatment (HR 2.34), while there was a higher incidence of MSSA-PJI treatment failure after therapy. Rifampin-based combinations exhibited an independent protective effect. Other independent predictors of outcome were polymicrobial, inflammatory, and bacteremic infections requiring more than 1 debridement, immunosuppressive therapy, and the exchange of removable components of the prosthesis.. This is the largest series of PJI by S. aureus managed with DAIR reported to date. The success rate was 55%. The use of rifampin may have contributed to homogenizing MSSA and MRSA prognoses, although the specific rifampin combinations may have had different efficacies.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Prognosis; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure; Treatment Outcome

Rifampin combination therapy plays an important role in the management of staphylococcal periprosthetic joint infection (PJI). However, the emergence of rifampin resistance is a feared complication. We retrospectively analysed predetermined potential risk factors in patients with rifampin-resistant staphylococcal PJI in a multicentre case-control study.. Cases (n = 48) were defined as PJI caused by rifampin-resistant staphylococci. Rifampin-susceptible controls (n = 48) were matched for microorganism and type of prosthetic joint. Uni- and multivariable conditional logistic regression analyses were performed to estimate odds ratios (OR) with 95 % confidence intervals (95 % CI).. Forty-eight cases (31 men; median age 67 years; age range 39-88 years) with hip- (n = 29), knee- (n = 13), elbow- (n = 4), shoulder- (n = 1) or ankle-PJI (n = 1) were enrolled in the study. Staphylococcus aureus and coagulase-negative staphylococci were isolated in ten and 38 episodes, respectively. Most of the cases (n = 44, 92 %) had a previous PJI, and 93 % (n = 41) of these had been treated with rifampin. There was an independent association of emergence of rifampin resistance with male sex (OR 3.6, 95 % CI 1.2-11), ≥ 3 previous surgical revisions (OR 4.7, 95 % CI 1.6-14.2), PJI treatment with high initial bacterial load (inadequate surgical debridement, <2 weeks of intravenous treatment of the combination medication; OR 4.9, 95 % CI 1.6-15) and inadequate rifampin therapy (OR 5.4, 95 % CI 1.2-25).. Based on our results, extensive surgical debridement and adequate antibiotic therapy are needed to prevent the emergence of rifampin resistance.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Load; Case-Control Studies; Confidence Intervals; Drug Resistance, Bacterial; Female; Humans; Joint Diseases; Joint Prosthesis; Logistic Models; Male; Middle Aged; Odds Ratio; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Risk Factors; Staphylococcal Infections

The efficacy of daptomycin, imipenem, or rifampin with fosfomycin was evaluated and compared with that of daptomycin-rifampin in a tissue cage model infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Strain HUSA 304 was used. The study yielded the following results for MICs (in μg/ml): fosfomycin, 4; daptomycin, 1; imipenem, 0.25; and rifampin, 0.03. The study yielded the following results for minimum bactericidal concentration (MBC) (in μg/ml): fosfomycin, 8; daptomycin, 4; imipenem, 32; and rifampin, 0.5. Daptomycin-rifampin was confirmed as the most effective therapy against MRSA foreign-body infections. Fosfomycin combinations with high doses of daptomycin and rifampin were efficacious alternative therapies in this setting. Fosfomycin-imipenem was relatively ineffective and did not protect against resistance.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Daptomycin; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Foreign-Body Reaction; Fosfomycin; Imipenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections

The management of prosthetic joint infections remains a clinical challenge, particularly infections due to methicillin-resistant staphylococci. Previously, this infection was considered a contraindication to debridement and retention strategies. This retrospective cohort study examined the treatment and outcomes of patients with arthroplasty infection by methicillin-resistant staphylococci managed by debridement and retention in conjunction with rifampin-fusidic acid combination therapy. Over an 11-year period, there were 43 patients with infection by methicillin-resistant staphylococci managed with debridement and retention. This consisted of close-interval repeated arthrotomies with pulsatile lavage. Rifampin was combined with fusidic acid for the majority of patients (88%). Patients were monitored for a median of 33.5 months (interquartile range, 20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and 24-month estimates of infection-free survival of 86% (95% confidence interval [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors were associated with treatment failure: methicillin-resistant Staphylococcus aureus (MRSA) arthroplasty infection, a single surgical debridement or ≥4 debridements, and the receipt of less than 90 days of antibiotic therapy. Patients with infection by methicillin-resistant coagulase-negative staphylococci (MR-CNS) were less likely to fail treatment. The overall treatment success rate reported in this study is comparable to those of other treatment modalities for prosthetic joint infections by methicillin-resistant staphylococci. Therefore, the debridement and retention of the prosthesis and rifampin-based antibiotic therapy are a valid treatment option for carefully selected patients.

Topics: Aged; Anti-Bacterial Agents; Arthroplasty; Debridement; Disease-Free Survival; Drug Therapy, Combination; Female; Fusidic Acid; Humans; Joint Prosthesis; Male; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Treatment Failure

Topics: Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Combined Modality Therapy; Device Removal; Diagnosis, Differential; Drug Therapy, Combination; Dyspnea; Femoral Neck Fractures; Hip Prosthesis; Humans; Male; Ofloxacin; Pneumonia, Staphylococcal; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Tuberculosis, Miliary

The occurrence of mutations in methicillin-resistant Staphylococcus aureus (MRSA) during persistent infection leads to antimicrobial resistance but may also impact host-pathogen interactions. Here, we investigate the host-pathogen consequences of 2 mutations arising in clinical MRSA during persistent infection: RpoB H₄₈₁Y, which is linked to rifampicin resistance, and RelA F₁₂₈Y, which is associated with an active stringent response. Allelic exchange experiments showed that both mutations cause global transcriptional changes, leading to upregulation of capsule production, with attenuated virulence in a murine bacteremia model and reduced susceptibility to both antimicrobial peptides and whole-blood killing. Disruption of capsule biosynthesis reversed these impacts on innate immune function. These data clearly link MRSA persistence and reduced virulence to the same mechanisms that alter antimicrobial susceptibility. Our study highlights the wider consequences of suboptimal antimicrobial use, where drug resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.

Topics: alpha-Defensins; Animals; Bacterial Capsules; beta-Defensins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Female; Host-Pathogen Interactions; Humans; Immunity, Innate; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Phenotype; Polymorphism, Single Nucleotide; Rifampin; Staphylococcal Infections; Transcription Factor RelA; Transcription, Genetic; Up-Regulation; Virulence

Staphylococcus aureus is the main cause of diabetic foot infection with the patient's endogenous flora as the principal source. Nasal carriage of S. aureus has been identified as an important risk factor for the acquisition of diabetic foot infections.. The study assessment the associations of S. aureus with methicillin resistant S. aureus were isolation from diabetic foot infection and nasal carriage of the same patients and their antibiotic susceptibility profile.. Diagnosis of S. aureus and methicillin resistant S. aureus were carried out by using standard procedures. Antibiotic sensitivity profiles were determent by breakpoint dilution method.. Out of 222 S. aureus isolation, 139 (62.61%) were isolated from the diabetic foot and 83 (37.39%) from the nasal carriage. Seventy one (30.87%) of the patients were S. aureus infection diabetic foot with nasal carriage. Among diabetic foot infection and nasal carriage patients, 40.85% of S. aureus were considered as methicillin resistant S. aureus. Rifampicin (96.40%) and Levofloxacin (91.44%) were active against S. aureus.. Patients at strong risk for methicillin resistant S. aureus nasal carriage and subsequent diabetic foot infection with high resistance to antibiotics.

Topics: Adult; Aged; Anti-Bacterial Agents; Carrier State; Diabetic Foot; Female; Humans; Levofloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Nose; Ofloxacin; Rifampin; Risk Factors; Staphylococcal Infections

Infected wounds determined by cats' bites represent high costs to public health, and their adequate treatment relies on the knowledge of the antimicrobial susceptibility of bacterial agents found in the oral microbiota. Members of the genus Staphylococcus sp. belong to the microbiota of the oral mucosa of cats and are frequently involved in secondary infections of these wounds. This study aimed to evaluate the antimicrobial susceptibility of Staphylococcus species isolated from oral mucosa of cats. Samples were collected from 200 clinically healthy cats and processed by standard bacteriological methods and tested for susceptibility to a panel of 16 antimicrobials. A total of 212 staphylococci isolates were obtained from 141 of the 200 cats (70.5%), and more than one colony was recognized in 53 cases. Coagulase-negative species were most frequently found (89.6%) distributed among Staphylococcus xylosus (50.9%), Staphylococcus felis (27.4%), Staphylococcus simulans (6.1%) and Staphylococcus sciuri (5.2%). Coagulase-positive species (10.4%) were distributed among Staphylococcus aureus (4.7%) and Staphylococcus intermedius group (SIG) (5.7%). Regarding to antimicrobial resistance, 178 isolates (83.9%) were resistant to at least one antimicrobial, and rifampicin showed the best results with 100% of sensitive strains. Conversely, high rates of resistance were observed for penicillin and tetracycline (56.1%). The 212 staphylococci isolates and 30 (14.1%) strains were resistant to methicillin (on the disc susceptibility test) and may be preliminarily considered as methicilin-resistant staphylococci. In conclusion, this study reports important rates of antimicrobial resistance among the species of Staphylococcus isolated from clinical specimens of cats, which must be considered for the treating of cats' bites in humans.

Topics: Animals; Anti-Bacterial Agents; Bites and Stings; Brazil; Cats; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Mouth Mucosa; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus; Tetracycline

Staphylococcus lugdunensis is a coagulase-negative staphylococcus with aggressive and rapidly progressive infectious behavior. This organism has emerged as an important pathogen implicated in both community-acquired and nosocomial infections, including meningitis, brain abscess, catheter-related bacteremia, and ventriculoperitoneal shunt infection.. We report the first known case of Staphylococcus lugdunensis intracranial abscess in a pediatric hydranencephalic patient, caused by a ventriculoperitoneal shunt-related infection. Further magnetic resonance imaging (MRI) confirmed a large abscess within the cranium that demonstrated multiple loculations. The patient received externalization of the right occipital ventricular catheter with evacuation of the brain abscess. Medical management included one week of intrathecal antibiotic treatment, and she was discharged on long-term intravenous rifampin and vancomycin, leading to cure of the infection.. This case suggests that if Staphylococcus lugdunensis is identified, a virulent and prolonged clinical course with the production of destructive lesions, similar to those with S. aureus, should be expected. A course of antibiotic therapy and aggressive management that may include surgical treatment will be needed.

Topics: Anti-Bacterial Agents; Brain Abscess; Ceftriaxone; Child, Preschool; Female; Humans; Hydranencephaly; Injections, Spinal; Neurosurgical Procedures; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis; Vancomycin; Ventriculoperitoneal Shunt

Coagulase-negative staphylococci are the most common cause of late-onset sepsis in premature neonates. The optimal approach in persistent coagulase-negative staphylococcal bacteremia, despite adequate treatment with glycopeptides, is not well established. A retrospective study was conducted on preterm neonates with persistent coagulase-negative staphylococcal bacteremia treated with the combination of vancomycin-rifampicin. Ten cases were included, with a median gestational age of 26 weeks (range 24 weeks + 3 days-31 weeks + 4 days, interquartile range 25 weeks + 3 days-29 weeks + 3 days) and a median birth weight of 715 g (range 555-2,030). The median age at the onset of infection was 9 days (range 5-37). The most frequent clinical presentation was apnea or increased ventilatory support. Bacteremia persisted for a median of 9 (range 6-19) days until rifampicin initiation. Bacteremia was resolved in all cases on vancomycin-rifampicin with no serious side effects.. Our study provides data supporting the safety and efficacy of vancomycin-rifampicin combination for the treatment of persistent coagulase-negative staphylococcal bacteremia in preterm neonates.

Topics: Anti-Bacterial Agents; Bacteremia; Coagulase; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Infant, Premature; Male; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome; Vancomycin

The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-3-yl)methyl)guanidine} that targets the bacterial cell division protein FtsZ. In vitro studies with various bacterial FtsZ proteins reveal that the compound alters the dynamics of FtsZ self-polymerization via a stimulatory mechanism, while minimally impacting the polymerization of tubulin, the closest mammalian homologue of FtsZ. The FtsZ binding site of the compound is identified through a combination of computational and mutational approaches. The compound exhibits a broad spectrum of bactericidal activity, including activity against the multidrug-resistant pathogens methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), while also exhibiting a minimal potential to induce resistance. Taken together, our results highlight the compound as a promising new FtsZ-targeting bactericidal agent.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biphenyl Compounds; Cytoskeletal Proteins; Drug Resistance, Multiple; Enterococcus; Guanidines; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Polymerization; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship; Vancomycin Resistance

Topics: Adult; Amikacin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Cefuroxime; Cesarean Section; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Metronidazole; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Staphylococcal Infections; Teicoplanin; Trimethoprim; Wound Infection

Vancomycin is the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical complications like renal failure alters vancomycin pharmacokinetics, leading to drug accumulation and toxicity. This highlights the need to identify an effective substitute for treating MRSA infections when vancomycin cannot be used. We report the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis with septicaemia and a right upper lobe cavity caused by MRSA. The patient also presented with renal failure, which precluded the use of vancomycin for treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and the infection was successfully treated. This case report provides evidence of the effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia in situations where the use of vancomycin is contraindicated.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; India; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Renal Insufficiency; Rifampin; Sepsis; Staphylococcal Infections; Teicoplanin; Treatment Outcome

Methicillin-resistant Staphylococcus is a common cause of orthopaedic implant infections. In such cases, rifampicin is the antibiotic of choice, but it should not be administered alone to avoid the selection of resistant mutants. Linezolid has activity against resistant staphylococci and a high oral bioavailability; therefore, it could be a good option for combining with rifampicin. We describe 2 patients admitted to our hospital due to orthopaedic implant infections, who received combination therapy with linezolid and rifampicin. In both cases, the trough serum concentration of linezolid during rifampicin treatment was below the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC(90)) for staphylococci, but increased after rifampicin withdrawal. This finding suggests an interaction between rifampicin and linezolid, and a possible explanation is discussed.

Topics: Acetamides; Adult; Aged, 80 and over; Anti-Bacterial Agents; Drug Interactions; Female; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Serum; Staphylococcal Infections

To compare the efficacy of in situ replacement with rifampicin-soaked silver-coated polyester (RSSCP) to that of expanded polytetrafluoroethylene (ePTFE) graft replacements in a porcine model for early aortic prosthetic vascular graft infection (PVGI).. Sixty pigs received polyester or silver-coated grafts with an 8 mm diameter implanted end-to-end in the infrarenal aorta, and the grafts were inoculated with approximately 10(6)Staphylococcus aureus. All developed S. aureus PVGI. Two weeks later, the 52 surviving pigs were randomised to undergo in situ graft replacement with ePTFE or RSSCP grafts followed by oral administration of 300 mg rifampicin and 750 mg ciprofloxacin twice a day, postoperatively. After three weeks, all pigs were sacrificed. In situ perigraft swabs and graft material were analysed for S. aureus quantitatively.. Only one out of 25 RSSCP grafts were infected with S. aureus, whereas 15 of 27 ePTFE grafts were infected after 3 weeks (OR = 0.022, 95% CI: 0.002, 0.219, P = 0.001).. In situ replacement with RSSCP grafts and oral rifampicin plus ciprofloxacin is more efficiency in eradicating S. aureus PVGI than ePTFE grafts treated with same oral antibiotics in a porcine aortic PVGI model.

Topics: Animals; Anti-Bacterial Agents; Aorta, Abdominal; Biocompatible Materials; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Ciprofloxacin; Device Removal; Disease Models, Animal; Polyesters; Polymers; Polytetrafluoroethylene; Prosthesis-Related Infections; Reoperation; Rifampin; Silver Compounds; Staphylococcal Infections; Staphylococcus aureus; Swine

We compared the MBEC™-HTP assay plates made of polystyrene with metal discs composed of TMZF(®) and CrCo as substrates for biofilm formation.. Staphylococcus aureus was grown on polystyrene and on metal discs made of titanium and chrome-cobalt. Antibiotic susceptibility was assessed by examining the recovery of cells after antibiotic exposure and by measuring the biofilm inhibitory concentration (BIC). The minimal inhibitory concentration (MIC) was assessed with planktonic cells. Bacterial growth was examined by scanning electron microscopy. The antibiotic concentration for biofilm inhibition (BIC) was higher than the MIC for all antibiotics. Microscopic images showed the biofilm structure characterized by groups of cells covered by a film.. All models allowed biofilm formation and testing with several antibiotics in vitro. Gentamicin and rifampicin are the most effective inhibitors of Staph. aureus biofilm-related infections. We recommend MBEC™-HTP assay for rapid testing of multiple substances and TMZF(®) and CrCo discs for low-throughput testing of antibiotic susceptibility and for microscopic analysis.. In vitro assays can improve the understanding of biofilms and help developing methods to eliminate biofilms from implant surfaces. One advantage of the TMZF(®) and CrCo discs as biofilm in vitro assay is that these metals are commonly used for orthopaedic implants. These models are usable for future periprosthetic joint infection studies.

Topics: Anti-Bacterial Agents; Biofilms; Gentamicins; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Polystyrenes; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Since 2001, several studies have reported high rifampicin resistance rates (45 - 100%) among methicillin-resistant Staphylococcus aureus (MRSA) isolates from South Africa. The authors previously characterised 100 MRSA isolates from hospitals in Cape Town, South Africa; forty-five percent of these isolates were rifampicin-resistant. The majority (44/45) corresponded to ST612-MRSA-IV, which is prevalent in South Africa, but has not been reported frequently elsewhere. The remaining rifampicin-resistant isolate corresponded to ST5-MRSA-I. The aim of this study was to investigate further the prevalence and genetic basis of rifampicin-resistance in MRSA isolates from hospitals in Cape Town.. Between July 2007 and June 2011, the prevalence of rifampicin-resistant MRSA in hospitals in Cape Town ranged from 39.7% to 46.4%. Based on the results of the aforementioned study, nine ST612-MRSA-IV isolates, the rifampicin-resistant ST5-MRSA-I isolate, and two rifampicin-susceptible MRSA isolates were investigated. Four previously described ST612-MRSA-IV isolates, including two each from South Africa and Australia, were also included.The ST5-MRSA-I isolate carried a single mutational change, H481Y, commonly associated with high-level rifampicin resistance. All ST612-MRSA-IV isolates carried an uncommon double amino acid substitution in RpoB, H481N, I527M, whilst one of the Australian ST612-MRSA-IV isolates carried an additional mutation within rpoB, representing a novel rpoB genotype: H481N, I527M, K579R. All ST612-MRSA-IV isolates also shared a unique silent single nucleotide polymorphism (SNP) within rpoB.. That local ST612-MRSA-IV isolates described here share an uncommon rpoB genotype and a unique silent SNP suggests this clone may have undergone clonal expansion in hospitals in Cape Town. Further, the data suggest that these isolates may be related to rifampicin-resistant ST612-MRSA-IV previously described in South Africa and Australia.

Topics: Anti-Bacterial Agents; DNA Mutational Analysis; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genotype; Hospitals; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Rifampin; South Africa; Staphylococcal Infections

Staphylococcus aureus small-colony variants (SCVs) persist intracellularly, which may contribute to persistence/recurrence of infections and antibiotic failure. We have studied the intracellular fate of menD and hemB mutants (corresponding to menadione- and hemin-dependent SCVs, respectively) of the COL methicillin-resistant S. aureus (MRSA) strain and the antibiotic pharmacodynamic profile against extracellular (broth) and intracellular (human THP-1 monocytes) bacteria. Compared to the parental strain, SCVs showed slower extracellular growth (restored upon medium supplementation with menadione or hemin), reduced phagocytosis, and, for the menD SCV, lower intracellular counts at 24 h postinfection. Against extracellular bacteria, daptomycin, gentamicin, rifampin, moxifloxacin, and oritavancin showed similar profiles of activity against all strains, with a static effect obtained at concentrations close to their MICs and complete eradication as maximal effect. In contrast, vancomycin was not bactericidal against SCVs. Against intracellular bacteria, concentration-effect curves fitted sigmoidal regressions for vancomycin, daptomycin, gentamicin, and rifampin (with maximal effects lower than a 2-log decrease in CFU) but biphasic regressions (with a maximal effect greater than a 3-log decrease in CFU) for moxifloxacin and oritavancin, suggesting a dual mode of action against intracellular bacteria. For all antibiotics, these curves were indistinguishable between the strains investigated, except for the menD mutant, which systematically showed a lower amplitude of the concentration-effect response, with markedly reduced minimal efficacy (due to slower growth) but no change in maximal efficacy. The data therefore show that the maximal efficacies of antibiotics are similar against normal-phenotype and menadione- and hemin-dependent strains despite their different intracellular fates, with oritavancin, and to some extent moxifloxacin, being the most effective.

Topics: Anti-Bacterial Agents; Cell Line; Daptomycin; Gentamicins; Glycopeptides; Hemin; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Monocytes; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vitamin K 3

Perioperative infection of an aortic graft is one of the most devastating complications of vascular surgery, with a mortality rate of 10% to 30%. The rate of amputation of the lower limbs is generally >25%, depending on the graft material, the location of the graft and infection, and the bacterial virulence. In vitro studies suggest that an antibiotic-impregnated graft may help prevent perioperative graft infection. In a pilot animal study, we tested a locally developed technique of bonding Dacron aortic grafts with three antimicrobial agents to evaluate the ensuing synergistic preventive effect on direct perioperative bacterial contamination.. We surgically implanted a 6-mm vascular knitted Dacron graft in the infrarenal abdominal aorta of six Sinclair miniature pigs. Two pigs received unbonded, uninoculated grafts; two received unbonded, inoculated grafts; and two received inoculated grafts that were bonded with chlorhexidine, rifampin, and minocycline. Before implantation, the two bonded grafts and the two unbonded grafts were immersed for 15 minutes in a 2-mL bacterial solution containing 1 to 2 × 10(7) colony-forming units (CFU)/mL of Staphylococcus aureus (ATCC 29213). Two weeks after graft implantation, the pigs were euthanized, and the grafts were surgically excised for clinical, microbiologic, and histopathologic study.. The two bonded grafts treated with S aureus showed no bacterial growth upon explant, whereas the two unbonded grafts treated with S aureus had high bacterial counts (6.25 × 10(6) and 1.38 × 10(7) CFU/graft). The two control grafts (unbonded and untreated) showed bacterial growth (1.8 × 10(3) and 7.27 × 10(3) CFU/graft) that presumably reflected direct, accidental perioperative bacterial contamination; S cohnii ssp urealyticus and S chromogenes, but not S aureus, were isolated. The histopathologic and clinical data confirmed the microbiologic findings. Only pigs that received unbonded grafts showed histopathologic evidence of a perigraft abscess.. Our results suggest that bonding aortic grafts with this triple antimicrobial combination is a promising method of reducing graft infection resulting from direct postoperative bacterial contamination for at least 2 weeks. Further studies are needed to explore the ability of this novel graft to combat one of the most feared complications in vascular surgery.

Topics: Animals; Anti-Infective Agents; Aorta, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Chlorhexidine; Coated Materials, Biocompatible; Disease Models, Animal; Drug Therapy, Combination; Minocycline; Pilot Projects; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Swine; Swine, Miniature; Time Factors

To report a case of multidrug-resistant osteomyelitis successfully treated with telavancin, rifampin, and meropenem.. An 18-year-old male with spina bifida was treated primarily in the outpatient setting over the course of 133 days with multiple antimicrobials for a recurrent right calcaneal wound and osteomyelitis infection. Initial cultures were positive for methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus, which were treated with intravenous vancomycin 1 g every 12 hours, increased after 13 days to 1.5 g every 12 hours with addition of rifampin 300 mg twice daily, both of which were discontinued on day 22 due to leukopenia (white blood cell count 3.0 × 10(3)/μL) and neutropenia (absolute neutrophil count 0.2 × 10(3)/μL). Daptomycin 8 mg/kg/day was then initiated with rifampin 300 mg twice daily; treatment was discontinued after 49 days due to an elevated creatine kinase level of 1831 U/L (baseline 86). Intravenous meropenem 1 g every 8 hours was again initiated on day 83 following additional identification of quinolone-resistant Pseudomonas aeruginosa from the soft tissue of the right foot. Intravenous vancomycin 1 g every 12 hours was also restarted at this time for persistent coagulase-negative Staphylococcus and oral rifampin 300 mg twice daily was again added. Adverse events again required the discontinuation of vancomycin on day 91. The eventual drug therapy regimen consisted of telavancin 750 mg/day for 42 days, meropenem for 50 days, and oral rifampin for 50 days. At the end of treatment, the patient's right heel wound had almost completely closed. He was without recurrence or treatment-related adverse events at follow-up 1 year later.. Antimicrobial selection for osteomyelitis infections presents a challenge to the clinician due to patient intolerance, increasing antimicrobial resistance, and variable antimicrobial penetration at the site of infection. To our knowledge, this is the first case report of the successful use of a regimen including telavancin for the treatment of a recurrent, coagulase-negative Staphylococcus osteomyelitis infection.. In this complex case involving a polymicrobial infection of the right calcaneal bone and surrounding soft tissue, eventual drug therapy including telavancin, meropenem, and rifampin resulted in a successful clinical response.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Coinfection; Drug Therapy, Combination; Humans; Lipoglycopeptides; Male; Meropenem; Osteomyelitis; Rifampin; Staphylococcal Infections; Thienamycins; Treatment Outcome

Staphylococcus epidermidis is the most common pathogen associated with infections of surgical implants and other prosthetic devices owing to its adhesion and biofilm-forming ability on biomaterials surfaces. The objective of this study was to compare susceptibilities of biofilm-grown cells to single antibiotic and in combination with others to identify those that were effective against S. epidermidis biofilms.. Biofilms were grown in the MBEC™ assay system. The use of this methodology allowed a rapid testing of an array of antibiotics alone (eight) and in combination (25 double combinations). The antibacterial effect of all treatments tested was determined by colony forming units (cfu) enumeration method.. The MBEC™ assay system produced multiple and reproducible biofilms of S. epidermidis. Although none of the antibiotics tested have demonstrated an antimicrobial effect (log reduction >3) against all S. epidermidis isolates biofilms, but combinations containing rifampicin showed in general a broader spectrum namely rifampicin-gentamicin and rifampicin-clindamycin. Levofloxacin in combination with rifampicin showed a killing effect against three isolates but failed to attain a bactericidal action against the other two.. Our findings showed that rifampicin should be a part of any antibiotic therapy directed against S. epidermidis biofilms. However, the efficient antibiotics combination might be dependent on S. epidermidis isolate being tested.

Topics: Biofilms; Clindamycin; Drug Combinations; Gentamicins; Humans; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

The authors report a rare case of piriformis pyomyositis, in a teenage rugby player, who was initially feverish and presented to us with low back pain, sciatica and inability to mobilise due to pain. Subsequent imaging investigations (MRI scan) revealed abscess formation in the piriformis muscle with compression effect on the ipsilateral sciatic nerve. A course of intravenous antibiotic therapy followed by oral antibiotics fully resolved his symptoms and returned inflammatory markers back to normal.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Floxacillin; Football; Humans; Low Back Pain; Magnetic Resonance Imaging; Male; Meropenem; Pain; Piriformis Muscle Syndrome; Pyomyositis; Rifampin; Sciatica; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Vancomycin

The present study was carried out to assess the frequency of methicillin-resistant staphylococci (MRS) among racehorses (n=209) and veterinary personnel (n=13) as well as environmental surfaces (n=14) at an equine hospital in Adana, Turkey. In addition, species distribution, antimicrobial susceptibility, resistance genes, staphylococcal chromosomal cassette mec (SCCmec) type and clonality of these isolates were also investigated. MRS were identified by 16S rRNA sequencing, and typed by pulsed-field gel electrophoresis (PFGE). As a result, MRS was isolated in horses (48.3%), clinic staff (92.3%) and environmental samples (71.4%). Of the 123 MRS isolates, 118 isolates were identified as Staphylococcus lentus, and the remaining ones were found to be S. sciuri (n=3), S. intermedius (n=1) and S. fleuretti (n=1). All isolates were found to be susceptible against vancomycin, quinupristin-dalfopristin and rifampicin. Additionally, single or various combinations of resistance genes were detected among MRS isolates. SCCmec type II was identified in all isolates. Similar PFGE patterns were observed among MRS isolated from horses, humans, and environmental samples. Since MRS were concurrently isolated from horses and humans it is suggested that cross-transmission of MRS between horses and humans might occur. However, it cannot be ruled out that transmission is human to animal or animal to human.

Topics: Animal Technicians; Animals; Cross Infection; DNA Primers; Electrophoresis, Gel, Pulsed-Field; Genes, MDR; Horse Diseases; Horses; Humans; Methicillin Resistance; Polymerase Chain Reaction; Rifampin; Species Specificity; Staphylococcal Infections; Staphylococcus; Turkey; Vancomycin; Virginiamycin

We studied the pharmacokinetic and pharmacodynamic parameters of levofloxacin and rifampicin in bone and joint infections. The optimal dose regimen of these two antibiotics has not been documented yet.. We performed plasma dosage for each antibiotic in patients with a bone and joint infection requiring treatment with a levofloxacin and rifampicin combination. We then computed the 6 hours post dose area under the concentration-time curve (AUC(0-6h)), the peak plasma concentration (Cmax), the area under the inhibitory concentration curve (AUIC), and the peak-to-minimum-inhibitory-concentration ratio (Cmax/MIC). The pharmacodynamic results were then compared to the published thresholds of effectiveness. The doses used were levofloxacin 500 mg bid and rifampicin 20mg/kg per day.. The plasma of 17 patients was dosed. The average AUC(0-6h) for levofloxacin was 46.59 mg.h/l, the average Cmax 10.7 mg/l, the average AUIC 932, and the average Cmax/MIC 107.5. The averages for rifampicin were 42.2mg.h/l, 11.8 mg/l, 11,125 and 1514. Given that bone concentration of levofloxacin is 30% that of the plasma concentration, that concentration was divided by three to estimate bone concentration.. The optimal thresholds of pharmacodynamic effectiveness were obtained for most patients with levofloxacin at 500 mg bid. Additional studies are still required to determine the optimal rifampicin dose.

Topics: Adult; Aged; Anti-Bacterial Agents; Area Under Curve; Arthritis, Infectious; Body Mass Index; Discitis; Dose-Response Relationship, Drug; Female; Fracture Fixation, Internal; Gastrointestinal Diseases; Humans; Levofloxacin; Male; Middle Aged; Musculoskeletal Diseases; Ofloxacin; Osteitis; Prospective Studies; Prosthesis-Related Infections; Rifampin; Sacroiliitis; Staphylococcal Infections; Surgical Wound Infection

We report herein on a case with multiple MRSA prosthetic arthritis and osteomyelitis successfully treated medically. Our patient was a 64-year-old Japanese woman with a previous medical history of malignant rheumatoid arthritis and multiple surgical interventions with an atlantoaxial fixation in 2003, artificial joint replacement of both knee joints in 2006, and of the right hip joint in September, 2007. She was initially hospitalized due to MRSA arthritis in the right hip in October, 2007. Thereafter, multiple joint infections occurred sequentially in the right knee joint in January 2008 and the left hip joint in June 2008. More recently, the patient was re-admitted in January 2009 due to cervical osteomyelitis with MRSA infection. The patient had been treated with a combination of vancomycin and rifampin for 17 weeks and followed by sulfamethoxazole/trimetoprim in the out-patient setting up to the present. Although the complete resolution of multiple deep MRSA infections with prosthetic arthritis and osteomyelitis is not expected without removing the infectious sources, our patient was successfully treated with chronic antibiotic suppressive therapy. Therefore, we report on our case with a literature review.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Female; Humans; Knee Joint; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Linezolid is being increasingly used in the treatment of infections with gram-positive organisms especially methicillin resistant Staphylococcal isolates. Though resistance to this antimicrobial is emerging but it is extremely rare. Here we document first case of linezolid resistant Staphylococcus haemolyticus (S.haemolyticus) from India. This organism was isolated from pus oozing from a postsurgical site in 61 year old male hailing from an adjoining state of Haryana.

Topics: Acetamides; Anti-Bacterial Agents; Clindamycin; Drug Resistance, Multiple, Bacterial; Hip Fractures; Humans; India; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus haemolyticus; Surgical Wound Infection; Treatment Outcome

Staphylococcus aureus (S. aureus) is a major nosocomial pathogen that causes a variety of infections and toxicoses. In recent years, the percentage of rifampicin-resistant S. aureus has increased rapidly in China. The aims of this study were to analyze 1) the level of rifampicin resistance in S. aureus and its correlation with mutations in the rpoB gene, and 2) the molecular characterization of rifampicin-resistant S. aureus isolates.. 88 rifampicin-resistant S. aureus isolates were collected for this study. Of the 88 isolates, 83 (94.3%) were high-level rifampicin resistant (MIC≥8 mg/L) while the remaining 5 isolates (5.7%) had a low-level resistance to rifampicin (MIC, 2 to 4 mg/L). Four amino acid substitutions were found in the 88 isolates, which were 481His/Asn (95.5%), 466Leu/Ser (87.5%), 477Ala/Asp (6.8%) and 486Ser/Leu (4.5%) respectively. All mutations were found to be present in cluster I of the rpoB gene. The low-level resistant isolates were found to have only one mutation, while the high-level resistant isolates had at least two or more mutations. The most common multiple mutations were 481His/Asn+466Leu/Ser(92.8%,77/83). The other multiple mutations found were 481His/Asn+477Ala/Asp (6.0%,5/83), and 481His/Asn+466Leu/Ser+477Ala/Asp (1.2%,1/83). Out of 28 high-level rifampicin-resistant S. aureus isolates, three molecular types were found, namely, ST239-MRSA-III-spa t030 (25/28, 89.3%), ST239-MRSA-III-spa t021 (2/28, 7.1%), and ST239-MRSA-III-spa t045 (1/28, 3.6%).. Rifampicin resistance in S. aureus was closely associated with mutations in the rpoB gene. High-level rifampicin-resistant S. aureus is one of the most important features in Anhui Provincial Hospital, and high-level rifampicin resistance in S. aureus is associated with multiple mutations of rpoB gene. The prevalence of high-level rifampicin-resistant S. aureus in Anhui may be associated with the spread of the ST239-MRSA III-spa t030 clone.

Topics: Amino Acid Substitution; China; Cross Infection; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Mutation, Missense; Rifampin; Sequence Analysis, DNA; Staphylococcal Infections; Staphylococcus aureus

Farnesol is a sesquiterpenoid that has been described as impairing bacterial growth. Therefore, the goal of this study was to compare the in vitro postantimicrobial effect (PAE) of farnesol against Staphylococcus epidermidis with the corresponding values of most common practice antibiotics and also to evaluate the combined effect of farnesol with these antibiotics against planktonic and biofilm cells.. After exposure of S epidermidis cells to farnesol and antibiotics at minimum inhibitory concentration for 1 hour, the cells were regrown in medium without any antimicrobial agent. Cellular viability was assessed by colony-forming units, every hour for 12 hours, and then, the PAE was determined. The combined effect of farnesol (0, 30, 100 and 300 μM) with vancomycin, tetracycline and rifampicin was also evaluated, by using these antibiotics at peak serum concentration.. When PAE is concerned, it was found that cells grown in 100 μM of farnesol behaved similarly to cells that had never been in contact with farnesol, whereas a clear difference was obtained with cells exposed to 300 μM of farnesol, displaying a longer PAE. Farnesol showed a combined effect with the tested antibiotics against planktonic cells, although this was not so evident against biofilm cells.. Despite the reduced efficacy against biofilm cells, farnesol seems to be a potential adjuvant therapeutic agent to antibiotics against S epidermidis planktonic cells. Moreover, its long PAE makes farnesol a potential candidate in the prevention of biofilm formation because it showed to be very effective against planktonic cells alone as well.

Topics: Anti-Bacterial Agents; Biofilms; Drug Therapy, Combination; Farnesol; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Microbial Viability; Plankton; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Stem Cells; Tetracycline; Time Factors; Vancomycin

A combination of vancomycin and rifampicin (rifampin) is commonly used to treat staphylococcal infections but its efficacy against methicillin-resistant Staphylococcus aureus (MRSA) biofilm is controversial. The objective of this study was to use a recently developed quantitative methodology to characterise the killing effect of vancomycin and rifampin combination against MRSA biofilm.. MRSA biofilm was exposed to escalating concentrations of vancomycin and rifampin and the viability of the biofilm-ensconced bacteria was evaluated. ADAPT II was used to model the concentration-effect relationship and determine the optimal sampling concentrations. Combination experiments were then conducted and the observations were compared with a simulated response surface representing null interaction. Finally, the pharmacodynamic interaction index (PDI) was computed as the ratio of the volumes under the observed and simulated surfaces.. In the combination experiments, all observations showed an inferior antibacterial effect to what is expected under null interaction assumption and the PDI was estimated to be 3.36 (95% CI, 3.25 to 3.46).. The results of the study demonstrate in-vitro antagonism between vancomycin and rifampin against MRSA biofilm. The quantitative approach employed to quantify the antibacterial effect of the combination provides a scientific rationale for further in-vivo investigations that should allow a better understanding of the therapeutic potential of this combination in biofilm-associated MRSA infections.

Topics: Anti-Bacterial Agents; Biofilms; Drug Interactions; Drug Therapy, Combination; Methicillin-Resistant Staphylococcus aureus; Models, Theoretical; Rifampin; Staphylococcal Infections; Vancomycin

Many strategies have been developed with the aim of reducing external ventricular drain-related infections. Antibiotic-impregnated catheters are one of them.. We report 648 cases of external ventricular drain from a total of 534 patients treated at the Virgen del Rocío Hospital between 1995 and 2006. Three subgroups were considered: group 1 included patients treated between 1995 and 2000, as well as a total of 190 external ventricular drains and 59 cases of infection (31.05%); group 2, with patients treated between 2000 and 2004 and managed with a minimal handling protocol, included 210 external ventricular drains and nine cases of infection (4.29%); and group 3, treated between 2004 and 2006, with 248 external ventricular drains and six cases of infection (2.41%). This latter subgroup included patients managed with a minimal handling protocol and antibiotic-impregnated catheters.. Infection rate was 17% when non-antibiotic-impregnated catheters were employed and 2.41% when antibiotic-impregnated catheters were inserted (p < 0.001). This difference was statistically significant before and after the introduction of a minimal handling protocol, with percentages of 5.31% and 3.27%, respectively (p < 0.001; odds ratio 0.08; absolute risk reduction 27.26%). However, no statistically significant difference was observed in infection rate when the impact of a minimal handling protocol was considered: 4.29% when only the protocol was introduced and 2.41% when both the protocol and antibiotic-impregnated catheters were used (p > 0.05).. Minimal handling protocols constitute an essential strategy in the reduction of external ventricular drain-related infections. Besides that, the use of antibiotic-impregnated catheters may reduce infection-related hospital costs.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Catheters, Indwelling; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Clindamycin; Coated Materials, Biocompatible; Cross Infection; Equipment Contamination; Humans; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Wound Infection; Vancomycin

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Biofilms; Combined Modality Therapy; Device Removal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Electrodes, Implanted; Endocarditis, Bacterial; Equipment Failure; Female; Humans; Pacemaker, Artificial; Postoperative Complications; Radiography, Interventional; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ultrasonography; Vancomycin

To study the incidence of rifampicin-resistant Staphylococcus aureus in Gipuzkoa, Northern Spain, and to characterize representative resistant isolates and mutations associated with resistance.. For rifampicin-resistant isolates, the rpoB gene fragment that includes the most frequent mutations conferring rifampicin resistance in S. aureus was amplified and sequenced. The role of new mutations responsible for rifampicin resistance was confirmed by cloning and complementation in trans. Resistant isolates were characterized by multilocus sequence typing and PFGE.. Between 1999 and 2008, 0.59% (96/16 348) of S. aureus clinical isolates studied showed rifampicin resistance. Rifampicin resistance was higher in methicillin-resistant S. aureus (MRSA) than in methicillin-susceptible S. aureus (MSSA) (3.26% versus 0.26%; P < 0.001). Twenty-two randomly selected rifampicin-resistant isolates were studied in depth, 11 showing low-level and 11 showing high-level rifampicin resistance (rifampicin MICs of 2-4 mg/L and ≥8 mg/L, respectively). Overall, 12 different mutations in the rpoB gene were detected, including a newly described N474K mutation followed by the insertion of a glycine residue at position 475. Among the eight different sequence types (STs) found, the most frequent were ST8 and ST863, the latter being associated with respiratory infections. Ten of the 11 low-level rifampicin-resistant isolates were MRSA ST8 and had the same H481N mutation, while the 11 high-level rifampicin-resistant isolates, 6 MSSA and 5 MRSA, belonged to eight different STs and had distinct rpoB mutations.. Low-level rifampicin-resistant isolates were mainly clonal while high-level resistant isolates showed a high genetic diversity. Most mutations observed coincided with those found in other studies, but a new mutation conferring rifampicin resistance was detected.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Child; Cloning, Molecular; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance; Electrophoresis, Gel, Pulsed-Field; Female; Genetic Complementation Test; Genotype; Humans; Incidence; Male; Middle Aged; Multilocus Sequence Typing; Polymorphism, Genetic; Respiratory Tract Infections; Rifampin; Sequence Analysis, DNA; Spain; Staphylococcal Infections; Staphylococcus aureus; Wound Infection; Young Adult

Staphylococcus epidermidis have become important causes of nosocomial infections, as its pathogenesis is correlated with the ability to form biofilms on polymeric surfaces. Production of poly-N-acetylglucosamine (PNAG) is crucial for S. epidermidis biofilm formation and is synthesized by the gene products of the icaADBC gene cluster. Production of PNAG/polysaccharide intercellular adhesin and biofilm formation are regulated by the alternative sigma factor, σ(B), and is influenced by a variety of environmental conditions including disinfectants and other antimicrobial substances. The susceptibility of five S. epidermidis strains to antibiotics alone and in double combination was previously tested. Our results demonstrated that some combinations are active and present a general broad spectrum against S. epidermidis biofilms, namely rifampicin-clindamycin and rifampicin-gentamicin. In the present study, it was investigated whether the combination of rifampicin with clindamycin and gentamicin and these antibiotics alone influence the expression of specific genes (icaA and rsbU) of S. epidermidis within biofilms using real-time polymerase chain reaction. The data showed that in most cases the expression of both genes tested significantly increased after exposure to antimicrobial agents alone and in combination. Besides having a similar antimicrobial effect, rifampicin combined with clindamycin and gentamicin induced a lower expression of biofilm-related genes relatively to rifampicin alone. Associated with the advantage of combinatorial therapy in avoiding the emergence of antibiotic resistance, this study demonstrated that it can also cause a lower genetic expression of icaA and rsbU genes, which are responsible for PNAG/polysaccharide intercellular adhesin production, and consequently reduce biofilm formation recidivism, relatively to rifampicin alone.

Topics: Acetylglucosamine; Amidohydrolases; Anti-Bacterial Agents; Biofilms; Clindamycin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Gene Expression Regulation, Bacterial; Gentamicins; Humans; Phosphoric Monoester Hydrolases; Polysaccharides, Bacterial; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Virulence

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) often display resistance to almost all classes of antimicrobial agents used in veterinary medicine. In the present study, we investigated the emergence of rifampicin resistance in MRSP, the persistence of these isolates and identified the corresponding mutations in the rpoB gene.. In addition to two rifampicin-resistant MRSP isolates from a multicentre study, consecutive MRSP isolates collected prior to and after rifampicin therapy from nine dogs at five Dutch veterinary hospitals were included in this study. The isolates were tested for resistance to rifampicin and other antimicrobial agents. The rifampicin resistance-determining region (RRDR) within the rpoB gene of the rifampicin-resistant and -susceptible isolates was amplified by PCR and sequenced. PFGE served to determine the genetic relationships of the MRSP isolates.. Two MRSP isolates of the multicentre study showed mutations at position 513 or 522 in the RRDR of the rpoB gene. In contrast to the rifampicin-susceptible isolates, all rifampicin-resistant MRSP isolates showed mutations at one or two of the amino acid positions 508, 509, 513, 516, 522, 526 and 531. In most strains, a single amino acid exchange was observed. PFGE analysis confirmed that the rifampicin-resistant MRSP isolates were indistinguishable from or closely related to the rifampicin-susceptible isolate obtained from the same dog prior to rifampicin application.. Therapy of MRSP infections with rifampicin results in the rapid emergence of rifampicin resistance and these isolates can persist for months. As a consequence, single therapy with rifampicin is not recommended.

Topics: Animals; Bacterial Typing Techniques; DNA Mutational Analysis; DNA-Directed RNA Polymerases; DNA, Bacterial; Dog Diseases; Dogs; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Methicillin-Resistant Staphylococcus aureus; Molecular Typing; Mutation, Missense; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; Staphylococcal Infections; Staphylococcus

The aim of this study was to determine the rifampicin (RIF) resistance rate of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients with MRSA bacteraemia who have or have not been exposed to RIF-containing antituberculous (anti-TB) treatment. From 2000 to 2008, patients with MRSA bacteraemia and previous exposure to RIF-containing anti-TB therapy were selected. Patients matched for sex, age and time of culture of MRSA bacteraemia but without exposure to anti-TB therapy were selected as a control group. A total of 139 patients, comprising 49 with RIF exposure and 90 without RIF exposure, were analysed. The RIF resistance rate was higher in patients with previous RIF exposure (61.2% vs. 20.0%; P<0.001). The minimum inhibitory concentration of RIF that inhibited 50% of MRSA isolates (MIC(50)) for the study group was also higher (128 mg/L vs. 0.015 mg/L; P<0.001). The mortality rate was higher in the study group (59.2% vs. 41.1%; P=0.041). MRSA isolates recovered from patients with current usage of a RIF-containing anti-TB regimen were more likely to be resistant to RIF (87.5% vs. 36%; P=0.001), with higher MIC(50) values (256 mg/L vs. 1mg/L; P=0.002), and resulted in a higher mortality rate than isolates from patients with remote usage of an anti-TB regimen (79.2% vs. 40%; P=0.005). Multivariate analysis showed that current anti-TB drug usage was the only risk factor for RIF resistance [odds ratio (OR)=7.457, 95% confidence interval (CI) 1.581-35.167] and mortality (OR=7.201, 95% CI 1.583-32.766). Given the high rate of RIF resistance in patients with prior anti-TB treatment, RIF susceptibility testing should be performed before considering combination treatment of RIF in MRSA infection.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood; Drug Resistance, Bacterial; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Tuberculosis

Topics: Anti-Bacterial Agents; Antidepressive Agents; Drug Resistance, Bacterial; Humans; Irritable Bowel Syndrome; Rifampin; Rifamycins; Rifaximin; Staphylococcal Infections; Staphylococcus

Shunts remain the commonest means by which hydrocephalus is treated. Despite the changes in valve and catheter technology, shunt infection and blockage are still a cause of great headache for the patient as well as the neurosurgeon. Antibiotic-laced catheters were proposed as a means by which to reduce shunt colonization and infection.. We present our experience of 52 months of Bactiseal catheters in all consecutive patients who underwent a ventriculoperitoneal (VP) shunt from July 2004 to November 2008, under the care of one neurosurgeon. This was a prospective study with outcome measures of infection, blockage, intra and postoperative complications and revision surgery.. One hundred and twenty-five patients underwent VP shunting with Bactiseal catheters, with a combination of NSC, Strata and Burr Hole valves. The age range of the patients was from 1 week premature to 64-years old. Forty-two of the patients were paediatric. The aetiology for hydrocephalus included posterior fossa tumoursto intra-ventricular haemorrhage, post-meningitic hydrocephalus and aqueduct stenosis. The overall complication rate was 12%. The following complications occurred: blockage in two cases; haemorrhage and blockage in two cases; CSF leak in one case; infection in four cases; other in three cases (peritoneal adhesions, wound erosion and postoperative peritonitis). There were four infections in total (3.2%). All of these occurred within six months of implantation. All infections were caused by rifampicin resistant Staphylococcus epidermidis.. In an era of increasing methicillin-resistant Staphylococcus aureus (MRSA) resistance and 'superbugs', is the use of antibiotic-laced catheters adding to the pool of resistant bacteria which may be harder to treat? Vigilance is required, as rare and resistant staphylococci strains occasionally can emerge as causative agents for VP shunt infections, in both adults and children, and their treatment can be difficult.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Catheter-Related Infections; Catheters; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Hydrocephalus; Infant; Infant, Newborn; Male; Middle Aged; Prospective Studies; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Outcome; Ventriculoperitoneal Shunt; Young Adult

Owing to their massive use, Staphylococcus epidermidis has recently developed significant resistance to several antibiotics, and became one of the leading causes of hospital-acquired infections. Current antibiotics are typically ineffective in the eradication of bacteria in biofilm-associated persistent infections. Accordingly, the paucity of effective treatment against cells in this mode of growth is a key factor that potentiates the need for new agents active in the prevention or eradication of biofilms. Daptomycin and linezolid belong to the novel antibiotic therapies that are active against gram-positive cocci. On the other hand, rifampicin has been shown to be one of the most potent, prevalent antibiotics against S. epidermidis biofilms. Therefore, the main aim of this study was to study the susceptibility of S. epidermidis biofilm cells to the two newer antimicrobial agents previously mentioned, and compare the results obtained with the antimicrobial effect of rifampicin, widely used in the prevention/treatment of indwelling medical device infections. To this end the in vitro activities of daptomycin, linezolid, and rifampicin on S. epidermidis biofilms were accessed, using these antibiotics at MIC and peak serum concentrations. The results demonstrated that at MIC concentration, rifampicin was the most effective antibiotic tested. At peak serum concentration, both strains demonstrated similar susceptibility to rifampicin and daptomycin, with colony-forming units (CFUs) reductions of approximately 3-4 log(10), with a slightly lower response to linezolid, which was also more strain dependent. However, considering all the parameters studied, daptomycin was considered the most effective antibiotic tested, demonstrating an excellent in vitro activity against S. epidermidis biofilm cells. In conclusion, this antibiotic can be strongly considered as an acceptable therapeutic option for S. epidermidis biofilm-associated infections and can represent a potential alternative to rifampicin in serious infections where rifampicin resistance becomes prevalent.

Topics: Acetamides; Biofilms; Colony Count, Microbial; Daptomycin; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA.. A tissue-cage infection model were used; therapy with tigecycline, vancomycin, rifampin, tigecycline plus rifampin and vancomycin plus rifampin was administered intraperitoneally for 7 days. The antibiotic efficacy was evaluated in the tissue-cage fluid and in the coverslips (attached bacteria); the emergence of resistance was screened.. Among monotherapies rifampin was the best treatment (decrease in log CFU/ml of tissue-cage fluid, 2.75) (P < 0.05). The addition of rifampin improved the efficacy of vancomycin (decrease, 2.28) and tigecycline (decrease, 1.56) in solitary; there were not significantly differences between tigecycline-rifampin (decrease, 3.39) and vancomycin-rifampin (decrease, 3.70), but only the latter was better than rifampin alone (P < 0.05). Resistant strains were only detected using rifampin alone.. tigecycline alone was the least effective treatment. Tigecycline-rifampin prevented the emergence of rifampin resistance, thus allowing the benefits of rifampin over time against staphylococcal foreign-body infections, but its efficacy needs to be evaluated in comparison with other anti-MRSA combined therapies.

Topics: Animals; Anti-Bacterial Agents; Diffusion Chambers, Culture; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Foreign Bodies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Models, Animal; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Tigecycline; Time Factors; Treatment Outcome; Vancomycin

Pelvic abscesses occurring after gynecologic pelvic surgery are uncommon. We describe the case of a woman who, after undergoing such a procedure, was found to have pelvic abscesses infected with methicillin-resistant Staphyloccocus aureus. The purpose of this report is to raise awareness of a life-threatening complication of gynecologic pelvic surgery.

Topics: Abscess; Anti-Bacterial Agents; Female; Genital Diseases, Female; Gynecologic Surgical Procedures; Humans; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pelvic Organ Prolapse; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Topics: Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Drainage; Female; Humans; Hydrocephalus; Male; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Variables associated with the outcome of patients treated for prosthetic joint infections (PJIs) due to Staphylococcus aureus are not well known.. The medical records of patients treated surgically for total hip or knee prosthesis infection due to S. aureus were reviewed. Remission was defined by the absence of local or systemic signs of implant-related infection assessed during the most recent contact with the patient.. After a mean posttreatment follow-up period of 43.6 ± 32.1 months, 77 (78.6%) of 98 patients were in remission. Retention of the infected implants was not associated with a worse outcome than was their removal. Methicillin-resistant S. aureus (MRSA)-related PJIs were not associated with worse outcome, compared with methicillin-susceptible S. aureus (MSSA)-related PJIs. Pathogens identified during revision for failure exhibited no acquired resistance to antibiotics used as definitive therapy, in particular rifampin. In univariate analysis, parameters that differed between patients whose treatment did or did not fail were: American Society of Anesthesiologists (ASA) score, prescription of adequate empirical postsurgical antibiotic therapy, and use of rifampin combination therapy upon discharge from hospital. In multivariate analysis, ASA score ≤2 (odds ratio [OR], 6.87 [95% confidence interval {CI}, 1.45-32.45]; P = .04) and rifampin-fluoroquinolone combination therapy (OR, 0.40 [95% CI, 0.17-0.97]; P = .01) were 2 independent variables associated with remission.. The results of the present study suggest that the ASA score significantly affects the outcome of patients treated for total hip and knee prosthetic infections due to MSSA or MRSA and that rifampin combination therapy is associated with a better outcome for these patients when compared with other antibiotic regimens.

Topics: Aged; Aged, 80 and over; Algorithms; Analysis of Variance; Anti-Bacterial Agents; Chi-Square Distribution; Female; Hip Prosthesis; Humans; Joint Diseases; Kaplan-Meier Estimate; Knee Prosthesis; Male; Middle Aged; Prognosis; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Severity of Illness Index; Staphylococcal Infections; Staphylococcus aureus; Treatment Failure

Daptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistant Staphylococcus aureus (MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 10(7) MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Although in vivo mean log(10) CFU/g of daptomycin-treated (4.23 ± 1.44; n = 12) or vancomycin-treated (4.63 ± 1.08; n = 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15; n = 9) (P < 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P < 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.

Topics: Animals; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Knee Prosthesis; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Vancomycin

Peritoneal dialysis patients are at an increased risk of Gram-positive organism infections because of disrupted skin barrier function, presence of a peritoneal catheter, and a deficient immunological system. In particular, the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is clinically challenging. Herein, we present a case of MRSA peritonitis that showed no response to a 14-day treatment with intraperitoneal vancomycin. To overcome unresponsiveness to vancomycin, we shifted the regimen to intraperitoneal daptomycin (given every 6 h through manual peritoneal dialysate exchanges) and oral rifampin (300 mg twice daily). The peritonitis resolved without sequelae or relapse. We suggest daptomycin and rifampin as an alternative combination therapy for MRSA infections that may otherwise remain unresolved.

Topics: Anti-Bacterial Agents; Catheters, Indwelling; Daptomycin; Drug Therapy, Combination; Female; Humans; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Rifampin; Salvage Therapy; Staphylococcal Infections; Treatment Outcome

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is associated with a high mortality rate. Treatment is challenging in patients with allergy to vancomycin. Herein, we describe a case of MRSA bacteremia secondary to medical device infection with MRSA that was complicated by MRSA meningitis. This case provides evidence for a possible role of combination therapy of daptomycin, linezolid, and rifampin in cases of MRSA meningitis and bacteremia.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Therapy, Combination; Humans; Linezolid; Male; Meningitis, Bacterial; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Rifampin; Staphylococcal Infections; Treatment Outcome

A majority of osteoarticular and implant-related infections are due to staphylococci and biofilm formation. Combined therapy including rifampicin is frequently recommended. Indeed, rifampicin penetrates biofilms and kills adherent staphylococci, but cannot be administered as monotherapy because of the rapid emergence of resistant mutants. While several antibiotic combinations including rifampicin have been implemented, evaluation of the clindamycin-rifampicin combination has been neglected, presumably because of the emergence of alternative combinations, such as quinolone-rifampicin, and the fear of potential antagonistic interactions. We report a limited series of 20 patients (3 immune-suppressed) with 6 arthroplasty infections, 4 other implant infections, 7 native arthritis, and 3 osteomyelitis, who were all successfully treated with this oral combination for >75% of the antibiotic course (median duration 45 days). The excellent outcomes obtained with this antimicrobial combination after a mean follow-up of 2.6 y (range 1.0-6.1 y) warrant further clinical and microbiological studies for implementing this regimen in routine practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clindamycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome; Young Adult

Nosocomial infections are a matter of concern in surgical wards. Their incidence is constantly increasing, especially among immunocompromised patients who are vulnerable to colonization by opportunistic pathogens such as Staphylococcus aureus. The bacterium accumulates resistance mechanisms against antibiotics such as vancomycin. The objective of our study was to explore this resistance, to screen for Staphylococcus aureus strains resistant to vancomycin, and to try various antibiotic combinations against these strains.. The antibiotic susceptibility of 220 S. aureus strains was determined by agar diffusion and evaluation of minimal inhibitory concentrations (MICs), by dilution technique on solid medium according to clinical and laboratory standard institute (CLSI) standards. The screening of strains resistant to vancomycin was performed on brain heart infusion agar medium, supplemented with 6μg/mL of vancomycin according to CLSI standards, and confirmed by determining MICs. The effectiveness of various antibiotic combinations was assessed by the checkerboard microplate method.. The results show multidrug resistance to agents known for their antistaphylococcal activity with fluctuations in the level of resistance.. Three strains proved resistant to vancomycin. The vancomycin/gentamycin combination was the most effective.

Topics: Adult; Aged; Algeria; Aminoglycosides; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Gentamicins; Hospitals, University; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Vancomycin; Vancomycin Resistance

Topics: Aged; Anti-Bacterial Agents; Contraindications; Daptomycin; Disease Progression; Drug Substitution; Echocardiography, Transesophageal; Endocarditis; Fatal Outcome; Fluid Therapy; Hepatic Encephalopathy; Hepatorenal Syndrome; Humans; Kidney Function Tests; Liver Transplantation; Male; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus lugdunensis; Vancomycin

Topics: Anti-Bacterial Agents; Catheter-Related Infections; Female; Humans; Male; Rifampin; Staphylococcal Infections; Ventriculoperitoneal Shunt

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Topics: Animals; Daptomycin; Endocarditis; Glycopeptides; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Methicillin-resistant Staphylococcus aureus (MRSA) has a high prevalence in Emergency Departments (EDs). The objective of this study was to determine the ability of emergency physicians to predict MRSA infection in purulent wounds. A prospective observational study was conducted in an urban, tertiary academic center in ED patients presenting with purulent wounds and abscesses that received wound culture. Physicians completed a questionnaire with patient demographic data and their own suspicion for MRSA infection in eligible patients. For emergency physician ability to predict positive culture for MRSA, sensitivities, specificities, and positive and negative likelihood ratios (LRs) were calculated. Risk factors were assessed for statistical significance using a chi-squared test with p < 0.05. There were 176 patients enrolled, and 19 were eliminated for incomplete data. Physician suspicion of MRSA had a sensitivity of 80% (95% confidence interval [CI] 71%-87%) and a specificity of 23.6% (95% CI 14%-37%) for the presence of MRSA on wound culture with a positive LR of 1.0 (95% CI 0.9-1.3) and a negative LR of 0.8 (95% CI 0.5-1.3). Prevalence was 64%. Only intravenous drug use was significantly associated with MRSA. Emergency physician's suspicion of MRSA infection is a poor predictor of MRSA infection.

Topics: Anti-Infective Agents; Emergency Service, Hospital; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prospective Studies; Rifampin; Sensitivity and Specificity; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Colony Count, Microbial; Dose-Response Relationship, Drug; False Negative Reactions; Humans; Minocycline; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Treatment of ventriculoperitoneal shunt infections frequently requires placement of an external ventricular drain (EVD). Surveillance specimens obtained from antibiotic-impregnated (AI) EVDs may be less likely to demonstrate bacterial growth, potentially resulting in undertreatment of an infection. The purpose of this study was to assess whether AI EVDs had any significant effect on bacterial culture results compared with nonantibiotic-impregnated (NAI) EVDs.. In vitro assays were performed using AI EVDs containing minocycline and rifampin (VentriClear II, Medtronic) and NAI EVD controls (Bioglide, Medtronic). The presence of antibiotics was evaluated via capillary electrophoresis of sterile saline drawn from AI and NAI EVDs after predefined incubation intervals. Antimicrobial activity was assessed by evaluating zones of inhibition created by the catheter aspirates on plates inoculated with a quality control strain of Staphylococcus epidermidis (American Type Culture Collection strain 12228). To determine the effects of cultures drawn through AI compared with NAI EVDs, the quality control strain was then incubated within 4 new AI and 4 new NAI EVDs for predefined intervals before being plated on culture media. Spread and streak plate culture results from each type of catheter were compared at each time interval.. Capillary electrophoresis showed that more minocycline than rifampin was eluted from the AI EVDs. Sterile saline samples incubated within the AI EVDs demonstrated zones of growth inhibition when placed on plates of S. epidermidis at all time intervals tested. No zones of inhibition were noted on NAI EVD control plates. When a standardized inoculum of S. epidermidis was drawn through AI and NAI EVDs, antimicrobial effects were observed after incubation in the AI EVD group only. Colony counting demonstrated that significantly fewer colonies resulted from samples drawn through AI compared with NAI EVDs at the multiple time intervals. Similarly, streak plating yielded a statistically significant number of false-negative results from AI compared with NAI EVDs at 2 time intervals.. The findings in the current study indicate that the risk of a false-negative culture result may be increased when a CSF sample is drawn through an AI catheter. In the management of a known shunt infection, a false-negative result from an EVD culture specimen may lead to an inappropriately short duration of antibiotic therapy. These data have significant clinical implications, particularly given the widespread use of AI drains and the current high rates of shunt reinfection after EVD use worldwide.

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid Shunts; Coated Materials, Biocompatible; Colony Count, Microbial; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Ventriculostomy

Methicillin-resistant S. aureus (MRSA) has been endemic in Hospital Universitari de Bellvitge, Barcelona, since 1990. During the 1990-95 period the Iberian clone (ST-247; SCCmec-I) was dominant. Isolates of clonal complex 5 (ST-125; SCCmec-IV) gradually replaced the Iberian clone from 1996 to 2003. A new multiresistant MRSA phenotype showing rifampicin resistance emerged in 2004 and rapidly increased from 25% in 2004 to 45% in 2006. The aims of this study were i) the molecular characterisation of rifampicin resistant MRSA isolates, ii) the study of the rifampicin resistance expression by disk diffusion, microdilution and E-test, and iii) the analysis of the rpoB gene mutations involved in rifampicin resistance.. A sample of representative 108 rifampicin-resistant MRSA isolates belonged to a single PFGE genotype, ST-228, SCCmec type I and spa type t041. Of 108 isolates, 104 (96%) had a low-level rifampicin resistance (MICs, 2 to 4 mg/L) and 4 a high-level rifampicin resistance (MICs, 128 - > or = 256 mg/L). Disk diffusion and E-test methods failed to identify a low-level rifampicin resistance in 20 and 12 isolates, respectively. A low-level rifampicin resistance was associated with amino acid substitution 481His/Asn in the beta-subunit of RNA polymerase. Isolates with a high-level rifampicin resistance carried additional mutations in the rpoB gene.. The emergence of MRSA clone ST228-SCCmecI, related to the Southern Germany clone, involved a therapeutical challenge for treating serious MRSA infections. Decreased susceptibility to rifampicin in MRSA strains of ST228-SCCmecI was associated with one or two specific mutations in the rpoB gene. One fifth of isolates with low-level rifampicin-resistance were missed by the diffusion methods.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Proteins; Bacterial Typing Techniques; Cross Infection; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Epidemiology; Mutation; Nucleic Acid Amplification Techniques; Rifampin; Spain; Staphylococcal Infections

In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. CoNS, and especially Staphylococcus epidermidis, transform into a stationary growth phase and produce biofilm when involved in a foreign body infection, making them difficult to eradicate with antimicrobials. Rifampicin has the ability to penetrate biofilm, but resistance may develop rapidly. To reduce the emergence of resistance, rifampicin should be combined with additional antimicrobials, of which several different ones have been proposed, including the relatively new class of antimicrobials, oxazolidinones, represented by linezolid. Thirty-seven CoNS isolates from patients with prosthetic joint infection were investigated by synergy testing using Etest. Nine antimicrobial combinations, based on either rifampicin or linezolid, were tested. For 16 (43%) of the isolates, a synergistic (n = 5), additive (n = 14) and/or antagonistic (n = 11) effect were identified. In conclusion, Etest is an objective and easily performed in vitro method for antimicrobial synergy testing. However, each isolate requires testing for the specific combination considered for treatment.

Topics: Acetamides; Anti-Infective Agents; Coagulase; Drug Synergism; Humans; Joint Prosthesis; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Prosthesis-Related Infections; Reproducibility of Results; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Topics: Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis; Fatal Outcome; Humans; Infant; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Vancomycin

To report a case in which daptomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was successfully treated with the addition of rifampin to daptomycin.. An 84-year-old male presented with fever and chills following cystoscopy. After culturing was conducted, the patient received single doses of vancomycin and gentamicin and then continued on vancomycin plus ceftazidime. Blood cultures grew MRSA, with vancomycin and daptomycin minimum inhibitory concentrations (MICs) of < or =1 microg/mL and 0.25 microg/mL, respectively. Vancomycin was continued, with trough concentrations maintained >15 microg/mL, but results of blood cultures remained positive. On day 10, therapy was switched to daptomycin 6 mg/kg/day, but culture results remained positive. On day 13, testing for vancomycin heteroresistance was negative, with the MIC unchanged. The vancomycin MIC remained unchanged on day 19, but the daptomycin MIC had increased to 2 microg/mL. Rifampin 300 mg orally twice daily was added on day 20; blood cultures obtained 2 days later were sterile. The patient was discharged to complete a 6-week course of antibiotics and was doing well 4 months following therapy.. Analysis of MRSA isolates obtained on days 1 and 19 showed an increase in the daptomycin MIC from 0.25 to 2 microg/mL. Because intervening isolates were not available for susceptibility testing, it is not possible to associate this increase with exposure to either vancomycin or daptomycin. Although in vitro synergy was not seen in this case, addition of rifampin to daptomycin therapy resolved the bacteremia.. In patients with persistent MRSA bacteremia, isolates should be retested for susceptibility to both daptomycin and vancomycin, including assessment for vancomycin heteroresistance. Addition of rifampin to daptomycin may be effective for persistent MRSA bacteremia, even if daptomycin MICs are elevated. Prospective studies are needed to define the role of combination therapy.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Therapy, Combination; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Urine

The aim of this study was to evaluate the efficacy and safety of rifampin for Staphylococcus aureus (SA) or coagulase negative staphylococci (CNS) prosthetic joint infection (PJI) treated with debridement and retention (D/R). We calculated the treatment failure cumulative incidence (TF) of a cohort of 101 patients with SA or CNS PJI treated with D/R and antimicrobial therapy. The effect of the use of a rifampin-based regimen was evaluated. Cox proportional hazards regression evaluated the association between treatment and time-to-TF controlling for the propensity to treat with rifampin and temporal confounders. Seven percent (1/14) of the prospective rifampin-treated patients, 32% (10/31) of the historical rifampin-treated patients and 38% (21/56) of the historical non-rifampin treated patients developed TF. After controlling for the propensity to treat with rifampin and American Society of Anesthesia scores, patients in the prospective cohort had a lower risk of TF compared to patients in the historical cohort not treated with rifampin (HR 0.11; 95%CI 0.01-0.84). None (0/14) of the patients in the prospective study developed hepatotoxicity. The outcome of staphylococcal PJI treated with D/R and rifampin-based regimens was better when compared with a historical cohort treated without rifampin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Debridement; Female; Humans; Liver; Male; Middle Aged; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome; Young Adult

Deep sternal wound infection (DSWI) is a severe complication after cardiac surgery, mostly caused by staphylococci. Little is known about the optimal antibiotic management.. A 10 year retrospective analysis of 100 patients with staphylococcal DSWI after cardiac surgery in a tertiary hospital. Treatment failure was defined as sternal wound dehiscence or fistula at the end of the prescribed antibiotic therapy, 12 months later, or DSWI-related death.. Most patients were male (83%) and the median age was 72 years [interquartile range (IQR) 63-76]. Coronary artery bypass was the most frequent preceding procedure (93%). The median time to diagnosis of DSWI was 13 days (IQR 10-18) after surgery. Clinical presentation consisted of wound discharge in 77% of patients. Coagulase-negative staphylococci were isolated in 54 and Staphylococcus aureus in 46 patients. All patients received antibiotics and 95% underwent surgical debridement. The median duration of antibiotic treatment was 47 days (IQR 41-78). During follow-up, 21 out of 100 patients experienced treatment failure. Of these, 8/21 patients (38%) died from DSWI after a median of 12 days (IQR 8-30). In the multivariate analysis, a rifampicin-containing antibiotic regimen was the only factor associated with lower risk of treatment failure (hazard ratio 0.26, 95% confidence interval 0.10-0.64, P = 0.004). Prolonged treatment (12 weeks instead of 6 weeks) did not alter outcome (P = 0.716) in patients without prosthetic valve endocarditis.. Treatment of rifampicin-susceptible staphylococcal DSWI with a rifampicin-containing antibiotic regimen may improve the outcome. After surgical debridement an antibiotic treatment of 6 weeks may be adequate for staphylococcal DSWI.

Topics: Aged; Anti-Bacterial Agents; Debridement; Humans; Male; Middle Aged; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Sternum; Surgical Wound Infection; Treatment Failure; Treatment Outcome

Topics: Anti-Bacterial Agents; Humans; Joint Prosthesis; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

It is a common practice to soak Titan(®) Coloplast penile implants in antibiotic solution prior to implantation. Aim.  The aim of this study is to identify an ideal solution for soaking the Titan(®) Coloplast penile implants prior to implantation.. Titan(®) strips were soaked in a different combination of antibiotics and the zone of inhibition was studied against Staphylococcus epidermidis and Escherichia coli. This zone of inhibition was compared against zone of inhibition produced by Inhibizone(®) -coated silicone strips. Zones of inhibitions were also compared for different components of Inhibizone(®) implant such as cylinder, tubing, connector, rear tip extender, and reservoir, and compared with similar components of Titan(®) Coloplast penile implants.. The zone of inhibition against S. epidermidis and E. coli for Titan strips dipped in Rifampin and Gentamicin was compared against other antibiotics. The clinical significance of dipping Titan(®) -coated Coloplast implant in Rifampin and Gentamicin solution was determined.. Rifampin 10mg/mL+gentamicin 1mg/mL (R10/G1) and rifampin 1mg/mL+gentamicin 1mg/mL (R1/G1) had excellent coverage against S. epidermidis and E. coli. The zone of inhibition (utilizing the Titan(®) coating) produced by both these solutions exceeds that produced by Inhibizone(®) by 40% to 56% for S. epidermidis and 33% for E. coli. Components of the American Medical System implant (tubing connectors and rear tip extenders) are not coated with antibiotics and had no zone of inhibition.. Soaking Titan(®) -coated Coloplast implants in R10/G1 solution produces a zone of inhibition greater than that produced by Inhibizone(®) -coated penile implants. The clinical significance of this increased zone of inhibition can only be determined by a separate clinical study.

Topics: Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Penile Implantation; Penile Prosthesis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Daptomycin has demonstrated clinical efficacy in the treatment of methicillin-resistant Staphylococcus aureus-associated bacteremia and right-sided infective endocarditis. Although daptomycin is not approved for treatment of gram-positive pneumonia, clinical evidence suggests that it may be effective therapy for S. aureus-associated septic pulmonary emboli (SPE). We present our clinical experience with the use of daptomycin in combination with rifampin in four patients with SPE in the absence of infective endocarditis. Three of the patients had a history of injection drug use; two of these patients also had soft-tissue infections. All patients had clinical resolution of their infections. Daptomycin and rifampin appear to have a role in the treatment of methicillin-resistant S. aureus bacteremia with SPE in the absence of infective endocarditis and should be considered in patients that have failed therapy with vancomycin.

Topics: Adult; Aged; Anti-Bacterial Agents; Daptomycin; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pulmonary Embolism; Radiography; Rifampin; Sepsis; Staphylococcal Infections; Treatment Outcome

Topics: Anti-Bacterial Agents; Body Fluids; Community-Acquired Infections; Daptomycin; Echocardiography, Transesophageal; Endocarditis; Female; Humans; Italy; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pericardiocentesis; Rifampin; Staphylococcal Infections; Treatment Outcome

Topics: Aged; Aged, 80 and over; Bacteremia; Drug Resistance, Bacterial; Female; Humans; Male; Methicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated-infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice showed bioluminescence and were culture-positive. In an antibiotic treated group, no bioluminescence was detected and only 20% of all primary implants and no tissue samples were culture-positive. After revision surgery, bioluminescence was detected in all control mice. All the implants and 80% of all tissue samples were culture-positive. In contrast, in the antibiotic treated group, 17% of all secondary implants and 33% of all tissue samples were culture-positive, despite antibiotic treatment. The study illustrates that due to the BAI of a primary implant, the infection risk of biomaterial implants is higher in revision surgery than in primary surgery, emphasizing the need for full clearance of the infection, as well as from surrounding tissues prior to implantation of a secondary implant.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Biofilms; Cross Infection; Equipment Contamination; Implants, Experimental; Mice; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs.. To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation.. Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections.

Topics: Animals; Anti-Bacterial Agents; Arthroplasty; Disease Models, Animal; Humans; Joint Diseases; Joints; Male; Mice; Mice, Inbred C57BL; Minocycline; Postoperative Complications; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. Daptomycin and vancomycin were compared, alone or in combination with rifampicin, over 4 days. Surviving bacteria were counted in bone, bone marrow and joint fluid. Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Bone and Bones; Bone Marrow; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Female; Joints; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

Community-associated methicillin-resistant Staphylococcus aureus infections are increasingly being documented worldwide. In Israel, however, CA-MRSA infections have not yet been reported, so awareness among physicians may be low.. To alert physicians to the possibility of CA-MRSA infection, which necessitates a distinct therapeutic approach.. We present three children with soft tissue infections caused by CA-MRSA who were treated in our medical center from January to March 2009.. In all three cases CA-MRSA was identified as the causative pathogen after surgical or spontaneous drainage. On susceptibility testing, the organisms were resistant to beta-lactam antibiotics but susceptible to clindamycin, rifampicin and trimethoprim-sulfamethoxazole.. Physicians should maintain an index of suspicion for CA-MRSA infections. The antibiotic-resistance profile of S. aureus should be watched carefully, and in particular, cultures should be obtained whenever soft tissue infections fail to respond to conventional treatment.

Topics: Adolescent; Anti-Bacterial Agents; Child, Preschool; Clindamycin; Community-Acquired Infections; Drug Combinations; Female; Humans; Israel; Male; Methicillin-Resistant Staphylococcus aureus; Rifampin; Soft Tissue Infections; Staphylococcal Infections; Sulfadoxine; Trimethoprim

To investigate the efficacy of daptomycin and rifampin either alone or in combination in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection.. Prospective, randomised, controlled animal study.. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony forming units of Staphylococcus aureus, strain Smith diffuse.. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received intra-peritoneal daptomycin, rifampin-soaked graft and daptomycin plus rifampin-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for S. aureus biofilms was performed to elucidate the same activity.. When tested alone, daptomycin and rifampin showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. The in vitro studies showed that minimum inhibitory concentration and minimum bactericidal concentration values for daptomycin were lower in presence of rifampin. Daptomycin prevented the emergence of rifampin resistance.. Daptomycin is an important candidate for prevention of staphylococcal biofilm-related infection and rifampin could serve as an interesting anti-staphylococcal antibiotic enhancer.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biofilms; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Colony Count, Microbial; Daptomycin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Male; Microbial Sensitivity Tests; Polyethylene Terephthalates; Prospective Studies; Prosthesis Design; Prosthesis-Related Infections; Random Allocation; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To test the time-dependent effects of rifampicin on established biofilms of Staphylococcus epidermidis isolated from patients with cardiac implant infections and catheter-related bacteremia.. Biofilms were grown in microtiter plates for 24 hours, dyed and stained with crystal violet. The mean optical density (OD) was used for quantification. The OD ratio (ODr = OD of the treated biofilm/OD of the untreated biofilm) was used to measure changes in the thickness of the biofilms over the time. Biofilms were incubated with rifampicin (0.6 mg/mL) for 1, 5, 15, 30 and 60 minutes. Unstained biofilms were sonicated and plated on Columbia agar for time-kill curves.. The incubation of the biofilms with rifampicin led to a significant reduction of the OD of the biofilms within 1 minute (ODr baseline: 1; ODr 1 min: 0.333 ± 0.131) (p<0.001). With regard to bacterial killing, rifampicin reduced the mean log count, but viable bacteria were still grown from biofilms in 13 out of 28 isolates despite MIC values < 0.01 mg/L.. In conclusion, our results confirm that rifampicin at a concentration of 1.2 mg/mL immediately reduces established biofilms formed by S. epidermidis although it is not bactericidal despite very low MICs at planktonic conditions.

Topics: Anti-Bacterial Agents; Biofilms; Catheter-Related Infections; Defibrillators, Implantable; Heart Valve Prosthesis; Humans; Microbial Sensitivity Tests; Microbial Viability; Pacemaker, Artificial; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Time Factors

The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 μg/ml and 4 μg/ml; vancomycin, 2 μg/ml and 4 μg/ml; linezolid, 2 μg/ml and >32 μg/ml; and rifampin, 0.03 μg/ml and 0.5 μg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Daptomycin; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxazolidinones; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Vancomycin

Device-related infections represent a significant clinical challenge. Once established, these infections prove difficult to treat with existing antibiotic regimens, compromising the health of device recipients, and usually requiring surgical intervention to resolve. The purpose of this study was to determine the ability of the AIGIS(RX)® Anti-Bacterial envelope to reduce the formation of bacterial biofilm on implanted pacing devices.. An infection was established in a rabbit model by creating bilateral subcutaneous implant pockets, into which a pacing device with or without AIGIS(RX)® was placed. The incisions were closed, and a defined dose of bacteria was infused into each implant pocket. After seven days, devices were explanted and assessed for viable bacteria by a sonication/vortex procedure to quantify bacteria, and by imaging of the device surface by scanning electron microscopy and laser scanning confocal microscopy.. The presence of the AIGIS(RX)® envelope eliminated recoverable, viable bacteria from the explanted devices using a vortex/sonication technique from in vivo models of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, and Escherichia coli infections. Scanning electron microscopy and confocal microscopy demonstrate greatly reduced biological material on the pacemaker surfaces in the presence of the AIGIS(RX)® envelope compared to untreated controls.. These results demonstrate that in this animal model, the AIGIS(RX)® device reduces the formation of adherent bacteria and reduces bioburden on implanted, infected pacemaker devices.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Disease Models, Animal; Drug Therapy, Combination; Equipment Contamination; Escherichia coli; Escherichia coli Infections; Microbial Viability; Microscopy, Confocal; Microscopy, Electron, Scanning; Minocycline; Pacemaker, Artificial; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Time Factors

Methicillin-resistant Staphylococcus aureus (MRSA) is a rare cause of cerebral abscesses, however it is a relatively more common etiologic agent in post-neurosurgical abscesses and the main antibacterial therapy option is vancomycin. In this report, a case of brain abscess due to MRSA which did not respond neither to moxifloxacin + vancomycin nor vancomycin + rifampin combination therapies, and merely treated by linezolid + rifampin combination, has been presented. Fifty-one years old female patient who was operated 40 days ago for subarachnoid bleeding and aneurysm in middle cerebral artery bifurcation, was hospitalized due to purulent leakage from the operation area. She did not have fever and her physical examination, including the neurologic system, was normal. Computerized tomography revealed an approximately 1 cm lesion compatible with subdural empyema and cerebral abscess in the right frontoparietal area in supratentorial sections. The patient was operated for wound revision and moxifloxacin was initiated. Since the operation materials revealed MRSA growth, vancomycin (4 x 500 mg, IV) was added to the treatment. The isolate was identified by conventional methods, and antibiotic susceptibility test performed by disk diffusion method showed that it was susceptible to levofloxacin, linezolid, rifampin, vancomycin and teicoplanin. Since no clinical response was obtained in two weeks, moxifloxacin was switched to rifampin (300 mg 1 x 2). On the 10th day of vancomycin + rifampin therapy, radiological findings showed development of cerebritis and therefore vancomycin was changed with linezolid (2 x 600 mg, IV). The control CT of the patient revealed regression of the brain lesion and linezolid + rifampin treatment continued for six weeks. The patient did not develop any hematological, liver or renal toxicity during the therapy and the radiological findings regressed. No relapse were detected in the one year follow-up period. This case suggested that linezolid might be a treatment alternative in the therapy of vancomycin-refractory MRSA brain abscess.

Topics: Acetamides; Anti-Infective Agents; Brain Abscess; Drug Therapy, Combination; Female; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Postoperative Complications; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Treatment Failure

Coagulase negative staphylococci (CoNS) are the most common cause of neonatal sepsis in the Neonatal Intensive Care Unit (NICU). A minority of neonates does not respond to vancomycin therapy and develops persistent bacteremia, which may be treated with rifampin. We evaluated the use of rifampin in persistent CoNS bacteremia.. Retrospective study of 137 neonates with CoNS bacteremia during admission to a tertiary NICU between July 2006 and July 2009. Main outcome measures were total duration of bacteremia and the adequacy of vancomycin and rifampin therapy.. 137/1696 (8.0%) neonates developed a CoNS bacteremia. Eighteen were treated with rifampin because of persistent bacteremia (3 positive blood cultures at least 48 hours apart with clinical symptoms) or (a serious suspicion of) an intravascular thrombus. Duration of bacteremia prior to rifampin therapy (8.0 ± 3.6 days) was positively correlated (p < 0.001) to the total duration of bacteremia (10.3 ± 3.7 days). After starting rifampin therapy C-reactive protein (CRP) levels of all neonates declined and blood cultures became sterile after 2.3 ± 1.6 days. Vancomycin levels were not consistently measured in all neonates, resulting in late detection of subtherapeutic trough levels.. Rifampin may be effective in the treatment of persistent CoNS infections in neonates. Outcome may be improved by adequate monitoring of vancomycin trough levels.

Topics: Bacteremia; C-Reactive Protein; Coagulase; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Male; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Blepharoplasty; Dexamethasone; Drug Therapy, Combination; Humans; Infusions, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Ophthalmic Solutions; Orbital Cellulitis; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Tobramycin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is a serious problem worldwide. To investigate the molecular epidemiology of MRSA isolates in China, a total of 702 MRSA isolates collected from 18 teaching hospitals in 14 cities between 2005 and 2006 were characterized by antibiogram analysis, pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome mec (SCCmec) typing, and spa typing; and 102 isolates were selected for multilocus sequence typing (MLST). Overall, SCCmec type III was the most popular type and was found in 541 isolates (77.1%), followed by SCCmec type II (109/702; 15.5%). Twenty-four PFGE types were obtained among 395 isolates collected in 2005, and 18 spa types were obtained among 702 isolates. spa type t030, which corresponded to PFEG types A to E, constituted 52.0% (365/702) of all isolates, and isolates of this type were present in all 14 cities; spa type t037, which corresponded to PFGE types F and G, accounted for 25.5% (179/702) of all isolates, and isolates of this type were identified in 12 cities. The two spa genotypes belonged to sequence type 239 (ST239) and carried SCCmec type III. spa type t002, which included isolates of PFGE types L to T, made up 16.0% (112/702) of the isolates that belonged to ST5 and SCCmec type II, and isolates of this type were distributed in 12 cities. The distribution of spa types varied among the regions. spa type t002 was the most common in Dalian (53.4%) and Shenyang (44.4%); spa type t037 was predominant in Shanghai (74.8%), whereas spa type t030 was the most common in the other cities. Two isolates from Guangzhou that harbored SCCmec type IVa with ST59 and ST88 were identified as community-associated MRSA. The prevalence of the Panton-Valentine leukocidin gene was 2.3%. The data documented two major epidemic MRSA clones, ST239-MRSA-SCCmec type III and ST5-MRSA-SCCmec type II, with unique geographic distributions across China.

Topics: Bacterial Proteins; China; Cross Infection; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Hospitals, Teaching; Humans; Leukocidins; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Staphylococcal Infections

We investigated the activity of linezolid, alone and in combination with rifampin (rifampicin), against a methicillin-resistant Staphylococcus aureus (MRSA) strain in vitro and in a guinea pig model of foreign-body infection. The MIC, minimal bactericidal concentration (MBC) in logarithmic phase, and MBC in stationary growth phase were 2.5, >20, and >20 microg/ml, respectively, for linezolid; 0.01, 0.08, and 2.5 microg/ml, respectively, for rifampin; and 0.16, 0.63, >20 microg/ml, respectively, for levofloxacin. In time-kill studies, bacterial regrowth and the development of rifampin resistance were observed after 24 h with rifampin alone at 1x or 4x the MIC and were prevented by the addition of linezolid. After the administration of single intraperitoneal doses of 25, 50, and 75 mg/kg of body weight, linezolid peak concentrations of 6.8, 12.7, and 18.1 microg/ml, respectively, were achieved in sterile cage fluid at approximately 3 h. The linezolid concentration remained above the MIC of the test organism for 12 h with all doses. Antimicrobial treatments of animals with cage implant infections were given twice daily for 4 days. Linezolid alone at 25, 50, and 75 mg/kg reduced the planktonic bacteria in cage fluid during treatment by 1.2 to 1.7 log(10) CFU/ml; only linezolid at 75 mg/kg prevented bacterial regrowth 5 days after the end of treatment. Linezolid used in combination with rifampin (12.5 mg/kg) was more effective than linezolid used as monotherapy, reducing the planktonic bacteria by >or=3 log(10) CFU (P < 0.05). Efficacy in the eradication of cage-associated infection was achieved only when linezolid was combined with rifampin, with cure rates being between 50% and 60%, whereas the levofloxacin-rifampin combination demonstrated the highest cure rate (91%) against the strain tested. The linezolid-rifampin combination is a treatment option for implant-associated infections caused by quinolone-resistant MRSA.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Therapy, Combination; Foreign-Body Reaction; Guinea Pigs; Injections, Intraperitoneal; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Models, Animal; Oxazolidinones; Plankton; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log(10) number of CFU/ml (Delta log(10) CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Delta log(10) CFU/ml) > cefuroxime (3.56 Delta log(10) CFU/ml) > rifampin (1.86 Delta log(10) CFU/ml) > gentamicin (0.61 Delta log(10) CFU/ml) > azithromycin (0.21 Delta log(10) CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs.

Topics: Animals; Animals, Outbred Strains; Anti-Bacterial Agents; Colony Count, Microbial; Dicloxacillin; Dose-Response Relationship, Drug; Female; Humans; Mice; Microbial Sensitivity Tests; Peritoneum; Peritonitis; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

The prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) among 1,012 vancomycin-susceptible methicillin (meticillin)-resistant S. aureus isolates collected from 14 cities in China from 2005 to 2007 was 13 to 16%, as determined by a combination of (i) measurement by the modified population analysis profile-area under the curve method (PAP-AUC) and (ii) estimation from the measured sensitivity and specificity of a screening method. Two hundred isolates from blood were chosen as a subset for measurement of the sensitivities and the specificities of several previously described screening methods by using the results of PAP-AUC as the reference. During this testing, one isolate was found to be a vancomycin-intermediate S. aureus (VISA) strain so was not used in the evaluation of the screening tests. Of the other 199 isolates, 26 (13.1%) were hVISA, as assessed by PAP-AUC. A screening cascade of culturing the isolates on brain heart infusion agar containing teicoplanin (5 mg/liter) and then subjecting the positive isolates to a macro-Etest method was applied to the 812 non-blood isolates, yielding 149 positive results. From these results and by adjusting for sensitivity (0.423) and specificity (0.861), the prevalence was estimated to be 15.7%. The precision of that estimate was assessed by reapplying the screening cascade to 120 randomly selected isolates from the 812 non-blood isolates and simultaneously determining their heterogeneous vancomycin-intermediate susceptibility status by PAP-AUC. Because PAP-AUC is impractical for use with large numbers of isolates, the screening-based estimation method is useful as a first approximation of the prevalence of hVISA. Of the 27 VISA or hVISA isolates from blood, 22.2% and 74.1% were staphylococcal chromosome cassette mec types II and III, respectively, while 77.8% and 22.2% were agr type 1 and agr type 2, respectively; the MIC ranges were 0.5 to 4 mg/liter for vancomycin and 0.25 to 1 mg/liter for daptomycin.

Topics: Anti-Bacterial Agents; China; Cities; Drug Resistance, Multiple, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Vancomycin; Vancomycin Resistance

Five new steroids, norselic acids A-E (1-5), were isolated from the sponge Crella sp. collected in Antarctica. The planar structures of the norselic acids were established by extensive NMR spectroscopy and mass spectrometry studies, and the configuration of norselic acid A (1) was elucidated by X-ray crystallography. Norselic acid A displays antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), vancomycin-resistant Enterococcus faecium (VRE), and Candida albicans and reduces consumption of food pellets by sympatric mesograzers. Compounds 1-5 are also active against the Leishmania parasite at low micromolar levels.

Topics: Animals; Antarctic Regions; Anti-Infective Agents; Candida albicans; Enterococcus faecium; Leishmania; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Porifera; Staphylococcal Infections; Steroids; Vancomycin Resistance

In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. In this study, rpoB sequencing was used for simultaneous species identification and detection of rifampicin resistance in clinical staphylococci isolates. Forty-nine (96%) out of 51 isolates, representing 17 different Staphylococcus species according to the initial phenotypic species identification, were identified to the species level using rpoB sequencing. Furthermore, the two remaining isolates were Kocuria sp. and Corynebacterium sp. respectively, according to 16S rRNA sequencing. Comparison with the phenotypic diagnostics also revealed that 8 (16%) of the 49 isolates differed regarding identified species. Discrepant analysis confirmed the result of the rpoB sequencing for all except 2 of these isolates, which could not be distinguished as single species using 16S rRNA sequencing. Regarding detection of rifampicin resistance, isolates obtained pre- and post-treatment with rifampicin were examined. These isolates comprised S. aureus (7 patients) and S. lugdunensis (1 patient). Rifampicin resistance was mainly detected following short-term treatment with rifampicin in combination with isoxazolyl-penicillin, or long-term treatment with rifampicin and ciprofloxacin. Each rifampicin-resistant isolate displayed an identical rpoB sequence as their corresponding rifampicin-susceptible isolates except for one (n = 6) or two (n = 1) nonsynonymous single nucleotide polymorphisms, or insertion of one codon (n = 1). In conclusion, rpoB sequencing is a rapid, objective and accurate method of species identification and simultaneous detection of rifampicin resistance in staphylococci.

Topics: Aged; Aged, 80 and over; Bacterial Proteins; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Rifampin; Sequence Alignment; Staphylococcal Infections; Staphylococcus

This study evaluated vancomycin susceptibility and activity alone and in combination with rifampicin and tigecycline against low-biofilm- and high-biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates.. Forty MRSA isolates recovered from bloodstream infections were analysed. Susceptibilities were performed in planktonic and biofilm cultures by microbroth dilution. Biofilm production was determined using an adherent plate assay. Time-kill analysis was performed on six low- and six high-biofilm-producing isolates with 15 mg/L vancomycin alone and in combination with rifampicin or tigecycline at 4x MIC.. Vancomycin susceptibility displayed a 4-fold and an 8-fold increase in the MIC(50) and MIC(90), respectively, in the presence of biofilm. Rifampicin and tigecycline susceptibilities also increased in biofilms, but still remained within the susceptibility breakpoints except for a tigecycline MIC(90) of 1 mg/L. High biofilm production was detected in 60% of the isolates. In time-kill analysis, 15 mg/L vancomycin achieved bactericidal activity against only low-biofilm-producing strains with a 1.8 log(10) cfu/mL difference in bacterial kill compared with high-biofilm-producing strains (P < 0.001). Rifampicin alone had minimal activity, resulting in resistance. Tigecycline was minimally effective and was not bactericidal, but no difference was observed in the comparison of biofilm-producing strains. Vancomycin in combination with rifampicin or tigecycline was bactericidal against all strains (mean kill 4.5 +/- 0.5 log(10) cfu/mL), regardless of biofilm production.. Vancomycin exposures at 15 mg/L may not be adequate in eradicating biofilm-producing S. aureus. Alternative treatments or combination therapy should be explored to optimize outcomes in biofilm-associated infections.

Topics: Anti-Bacterial Agents; Bacteremia; Biofilms; Colony Count, Microbial; Drug Synergism; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Rifampin; Staphylococcal Infections; Tigecycline; Vancomycin

Although infections associated with penile implants are relatively infrequent, they result in serious medical consequences. Because treatment of these infections usually requires removal of the infected penile implant, prevention of infection is crucial. Since bacterial colonization of the implant is a prelude to clinical infection, antimicrobial modification of the devices may inhibit device colonization and subsequent infection.. We compared the spectrum and durability, both in vitro and in vivo, of two antibiotic-treated penile prostheses: InhibiZone implants pre-impregnated with minocycline and rifampin (M/R) and Titan implants dipped in vancomycin.. 1×1-cm cylinder segments of (1) control untreated, (2) M/R-impregnated, and (3) vancomycin-dipped implants were studied. Baseline zones of inhibition (ZI) were determined against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), and Escherichia coli. In addition, ZI against methicillin-susceptible S. aureus were compared both in vitro after being washed in a flow chamber and after subcutaneous implantation in rabbits for 1, 2, 7, and 14 d.. ZI were measured as the diameter of the clear zone around each test device minus the external diameter of the device.. Implants pre-impregnated with M/R displayed a broader spectrum of antimicrobial activity than vancomycin-dipped implants against both gram-positive and -negative bacteria. The M/R-impregnated devices also yielded significantly larger zones of inhibition against S. aureus than vancomycin-dipped implants, both in vitro (p<0.003) and in vivo throughout the 14-d period of device implantation in rabbits (p≤0.03).. Penile prostheses impregnated with M/R have a broader spectrum in vitro and a more durable antimicrobial activity in vitro and in an animal model than implants dipped in vancomycin. Therefore, along with being a more practical model for incorporating antimicrobials onto the device, the use of implants pre-impregnated with M/R may help reduce the incidence of penile implant infection.

Topics: Animals; Anti-Bacterial Agents; Drug Implants; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterococcus; Escherichia coli; Escherichia coli Infections; Male; Methicillin-Resistant Staphylococcus aureus; Minocycline; Penile Prosthesis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

A 26-year-old pregnant woman who was an intravenous drug user (IDU) was admitted to our hospital for the treatment of tricuspid valve infective endocarditis (IE) and lung abscesses due to methicillin-resistant Staphylococcus aureus (MRSA). We started to treat her with vancomycin (VCM) alone and then in combination with rifampicin (RFP), but her condition did not improve. Then we added sulfamethoxazole/trimethoprim (SMZ/TMP) to VCM and RFP. After that, she improved rapidly. In Japan, there are very few reports about tricuspid valve IE caused by MRSA in IDUs. This case suggests that the combination of VCM, RFP, and SMZ/TMP may be effective for the treatment of severe MRSA infections.

Topics: Adult; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Humans; Lung Abscess; Methicillin-Resistant Staphylococcus aureus; Pregnancy; Pregnancy Complications, Infectious; Pulmonary Embolism; Rifampin; Staphylococcal Infections; Substance Abuse, Intravenous; Tricuspid Valve; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Staphylococcus epidermidis is the most important pathogen in infections related to implanted foreign materials, especially prosthetic joint infections (PJIs). The aim of this study was to investigate the antimicrobial activities of 16 antibiotics against S. epidermidis isolated from PJIs, with special focus on rifampicin and rpoB variability. Ninety-one per cent of the isolates were multiresistant (i.e. resistant to members of more than three classes of antibiotics). Thirty-nine per cent were resistant to rifampicin, associated with one or two single-nucleotide polymorphisms (SNPs) in rpoB. Using IsoSensitest agar with supplements, 61% were resistant to oxacillin, and using Mueller-Hinton II agar with supplement, 84% were resistant. Using the Etest, 58% were resistant to cefoxitin, and using the disk diffusion test, 91% were resistant. The mecA gene was detected in 85% of the isolates. Regarding recently available antibiotics, all isolates were susceptible to tigecycline and linezolid, and 97% were susceptible to daptomycin. In addition, two novel antibiotics, dalbavancin and ceftobiprole, were tested, although not yet available for routine use. The MIC(50) and MIC(90) values of these novel antibiotics were 0.032 and 0.047 mg/L and 0.5 and 1.5 mg/L, respectively. Among the other antibiotics, the rates of resistance varied between 0% (vancomycin) and 82% (trimethoprim-sulphamethoxazole). S. epidermidis strains causing PJIs often show multiresistance, including resistance to rifampicin, which is mainly caused by one or two SNPs. Some of the newer antimicrobial agents may provide alternatives for monotherapy or combination therapy with rifampicin. Detection of mecA is necessary before initiating treatment of infections due to S. epidermidis when it displays intermediate susceptibility to cefoxitin.

Topics: Anti-Bacterial Agents; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Humans; Joint Prosthesis; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

The combination of levofloxacin and rifampin has been recommended for the treatment of staphylococcal prosthetic infection. In a rabbit model of prosthetic knee infection due to a susceptible clinical strain of Staphylococcus aureus, the combination of levofloxacin and rifampin was bactericidal, significantly reduced bacterial titers in bone compared with levels for rifampin and controls (P < 0.05), sterilized 6 of 12 animals, and prevented the selection of resistant mutants that was observed with rifampin alone, validating clinical recommendations.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Therapy, Combination; Humans; Knee Prosthesis; Levofloxacin; Methicillin; Microbial Sensitivity Tests; Ofloxacin; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 microg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 microg/ml, daptomycin reduced the counts by >3 log(10) CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 microg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log(10) CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log(10) CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

Topics: Animals; Chromatography, High Pressure Liquid; Cross Infection; Daptomycin; Drug Implants; Drug Therapy, Combination; Guinea Pigs; Male; Mass Spectrometry; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

Methicillin-resistant Staphylococcus aureus (MRSA) is a type of Staphylococcus that is resistant to certain antibiotics, such as methicillin, oxacillin, penicillin, and amoxicillin. This nosocomial pathogen has become a great threat in hospitals globally. Up to 40% of the normal population carries S. aureus in the anterior nares, and this rate is often higher in hospitalized patients and their attendants. This case report presents a patient with serious MRSA osteomyelitis of the mandible demonstrating purulent discharge. The patient failed to recover despite prolonged postoperative treatment and the administration of several antibiotics. There was a resulting nonunion along with chronic MRSA infection. The treatment protocol involved a multimodal approach with parenteral clindamycin infusion, local rifampicin irrigation, and intermaxillary fixation of the jaws.

Topics: Adult; Anti-Bacterial Agents; Bone Plates; Clindamycin; Fracture Fixation, Internal; Humans; Infusions, Intralesional; Male; Mandibular Diseases; Mandibular Fractures; Methicillin-Resistant Staphylococcus aureus; Osteomyelitis; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Therapeutic Irrigation; Treatment Outcome

Synthetic vascular conduits used in traumatic or infected fields have a high failure rate leading to catastrophic consequences including amputation and death. Although efforts to coat vascular grafts with antibiotics have had varying results, we developed a novel coating technique for expanded-polytetrafluoroethylene (ePTFE), which has proven to be effective in vitro. Thus, we hypothesized that the coated grafts would resist infection and have decreased neointimal hyperplasia when used in vivo in a large animal model.. Minocycline and rifampin suspended in a mixture of methacrylates were coated onto a 3cm segment of 6mm ePTFE (Bard, Tempe, AZ). An antibiotic-coated (ABX), adhesive-coated (AC), or control (C) ePTFE graft was then placed as an end-to-side graft into the left iliac artery of a male mongrel pig. Sterile saline or innoculum containing 3x10(8)Staphylococcus aureus (SA) or Staphylococcus epidermidis (SE) was then placed directly on the graft and the reflected peritoneum re-approximated to confine the bacteria. After 6 wk, the graft was harvested, cultured, and morphometric analyses of neointimal hyperplasia were performed.. Twenty-seven pigs had grafts placed (9 ABX, 9 AC, 9 C) and harvested. Of the nine grafts exposed to SA, the uncoated and adhesive-coated grafts averaged greater than 50,000 colonies of SA while the antibiotic-coated grafts averaged less than 50 colonies. Although not statistically significant, neointimal hyperplasia was decreased by 15% to 20% when using an ABX graft in an infected field.. The coated grafts appeared to decrease NIH formation although not significantly in this small pilot study. The methacrylate antibiotic-coated ePTFE graft did provide resistance to infection when used in infected fields.

Topics: Adhesives; Animals; Anti-Bacterial Agents; Blood Vessel Prosthesis; Coated Materials, Biocompatible; Disease Models, Animal; Hyperplasia; Male; Methacrylates; Microscopy, Electron, Scanning; Minocycline; Pilot Projects; Polytetrafluoroethylene; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Swine

Topics: Antibiotics, Antitubercular; Developing Countries; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections; Tuberculosis, Multidrug-Resistant

The purpose of this retrospective study was to describe a tertiary care center experience with different antibiotic strategies that include cloxacillin (C) in patients with severe septic bursitis (SB).. A severe SB was considered when the patient needed hospitalization and/or intravenous (i.v.) antibiotics. Patients were treated with bursal aspiration and one of these antibiotic options: C, 2 g/4 h per day i.v. until improvement, and afterwards 1 g/6 h per day v.o. until resolution; (C+G), gentamicin i.v. was added to C for 5 to 7 days (initial dose 240 mg/d); (C+R), rifampicin was added at a dose of 600 mg/d v.o.. The study comprised 82 patients with severe SB. The mean delay to diagnosis was 6.1+/-6.9 days, and the most frequent location was the prepatellar bursa. In 67%, the bursal fluid culture yield a positive result, being Staphylococcus aureus the most frequent bacteria isolated (94.4%). At admission, fever and extensive cellulites were more frequent in the C+G group. Patients in the C+G had a longer duration of i.v. antibiotics compared with the C group (p=0.008), although the total duration of antibiotics was not different. There was a tendency in the C+R group to need more surgery. All patients except one had a complete resolution and there were no differences in side effects.. In patients with severe SB without extensive cellulites i.v., C alone may be sufficient. In patients with a more severe presentation, C plus gentamicin seems to be an appropriate option in the majority of them.

Topics: Anti-Bacterial Agents; Bursa, Synovial; Bursitis; Cloxacillin; Drug Therapy, Combination; Elbow Joint; Female; Gentamicins; Hospitals, University; Humans; Injections, Intravenous; Knee Joint; Male; Middle Aged; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Conjunctivitis; Drug Therapy, Combination; Eye Infections, Bacterial; Humans; Male; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Orbital Diseases; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tobramycin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Staphylococcus lugdunensis is an infrequent cause of infective endocarditis (IE) and usually involves native valves of the heart. It causes life-threatening events such as rupture of cardiac valve or cerebral or pulmonary embolism due to necrosis on the endocardial tissue involved by the bacteria. Antibiotic therapy without cardiac surgery or delayed cardiac surgery usually follows a fatal course in S. lugdunensis endocarditis. In this report the first case of S. lugdunensis endocarditis from Turkey was presented. A 37-year-old man was admitted to the emergency department with a 2-weeks history of fever chills and accompanying intermittent pain on the left side of the thorax. Other than recurrent folliculitis continuing for 20 years, his history was unremarkable. Echocardiography revealed vegetation on the mitral valve of the patient and vancomycin plus gentamicin were initiated with the diagnosis of IE. All blood cultures (5 sets) taken on admission and within the initial 48 hours of the antibiotic therapy yielded S. lugdunensis. According to the susceptibility test results, the antibiotic therapy was switched to ampicillin-sulbactam plus rifampin. Blood cultures became negative after the third day of therapy, however, cardiac failure was emerged due to rupture of mitral valve and chorda tendiniea on the 12th day of the therapy. Cardiac surgery revealed that mitral valve and surrounding tissue of the valve were evidently necrotic and fragile, anterior leaflet of the mitral valve was covered with vegetation, posterior leaflet and chorda tendiniea were ruptured. Vegetation was removed and the destructed mitral valve was replaced with a mechanical valve. Vegetation culture remained sterile, however, antibiotics were switched to vancomycin plus rifampin due to persistent fever on the 21st day of the therapy (9th day of operation). Fever resolved four days after the antibiotic switch. Antibiotics were stopped on the 9th weeks of admission and the patient was discharged. He had no problem in follow-up controls for one year. In conclusion, proper antibiotic therapy combined with early cardiac surgery seems to be the optimal therapeutic approach in IE caused by S. lugdunensis.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Chemotherapy, Adjuvant; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve; Necrosis; Rifampin; Staphylococcal Infections; Staphylococcus; Sulbactam; Ultrasonography; Vancomycin

We retrospectively evaluated 105 patients at the Mayo Clinic between 1970 and 2006 with native valve endocarditis who underwent acute valve surgery. The objective was to determine if outcomes differed based on whether they had received an antibiotic regimen recommended for native valve endocarditis or one for prosthetic valve endocarditis. Fifty-two patients had streptococcal and 53 had staphylococcal infections. Patients with each type of infection were divided into two groups: the first received postoperative monotherapy (with a beta-lactam or vancomycin), and the second received combination therapy (with an aminoglycoside for streptococcal infection, and gentamicin and/or rifampin for staphylococcal infection). The duration and types of antibiotics given pre- and postoperatively, valve cultures results, antibiotic-related adverse events, relapses, and mortality rates within 6 months of surgery were analyzed. Cure rates were similar regardless of the regimen administered. With the small number of patients in each group, a multicenter study with a larger cohort of patients is needed to better define optimal postoperative treatment regimens in this population.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; beta-Lactams; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Retrospective Studies; Rifampin; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome; Vancomycin

We report a case of a 15-year-old boy who developed multiple organ failure secondary to a sport injury leading to infection with a Panton Valentine Leukocidin (PVL) secreting Community-Acquired Methicillin Sensitive Staphylococcus Aureus (CA MSSA). Aggressive antibiotic therapy eventually led to recovery.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Anticoagulants; Athletic Injuries; Bacterial Toxins; Community-Acquired Infections; Exotoxins; Floxacillin; Humans; Leukocidins; Male; Martial Arts; Methicillin Resistance; Multiple Organ Failure; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Warfarin

Five of the seven cases of vancomycin-resistant Staphylococcus aureus (VRSA) infection identified to date have occurred in southeastern Michigan. VRSA isolates from the four most recent cases (all from Michigan) were characterized. The vanA gene was localized to a single plasmid in each VRSA isolate. The pulsed-field gel electrophoresis patterns of chromosomal DNA and the restriction profile of the plasmid demonstrated that the four isolates were unique and differed from the first three VRSA isolates. Vancomycin-resistant Enterococcus (VRE) isolates, all of which were Enterococcus faecalis, were recovered from case patients 4 to 6. Each VRE isolate transferred vancomycin resistance to E. faecalis JH2-2 by conjugation. PCRs for vanA and the Inc18-like plasmid genes traA and repR confirmed the presence of an Inc18-like vanA plasmid in all VRE isolates and transconjugants. An Inc18-like vanA plasmid was identified in the VRSA isolate from case patient 7. These findings suggest a role of Inc18-like plasmids as vanA donors.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Conjugation, Genetic; DNA Transposable Elements; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecalis; Humans; Michigan; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Restriction Mapping; Staphylococcal Infections; Staphylococcus aureus; Vancomycin Resistance

Thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus can be isolated from the airway secretions of patients suffering from cystic fibrosis (CF) and are implicated in persistent and treatment-resistant infections. These characteristics, as well as the variety of mutations in the thymidylate synthase-encoding thyA gene which are responsible for thymidine dependency, suggest that these morphological variants are hypermutable. To prove this hypothesis, we analyzed the mutator phenotype of different S. aureus phenotypes, in particular CF-derived TD-SCVs, CF-derived isolates with a normal phenotype (NCVs), and non-CF NCVs. The comparative analysis revealed that the CF isolates had significantly higher mutation rates than the non-CF isolates. The TD-SCVs, in turn, harbored significantly more strong hypermutators (mutation rate > or = 10(-7)) than the CF and non-CF NCVs. In addition, antimicrobial resistance to non-beta-lactam antibiotics, including gentamicin, ciprofloxacin, erythromycin, fosfomycin, and rifampin, was significantly more prevalent in TD-SCVs than in CF and non-CF NCVs. Interestingly, macrolide resistance, which is usually mediated by mobile genetic elements, was conferred in half of the macrolide-resistant TD-SCVs by the point mutation A2058G or A2058T in the genes encoding the 23S rRNA. Sequence analysis of mutS and mutL, which are involved in DNA mismatch repair in gram-positive bacteria, revealed that in hypermutable CF isolates and especially in TD-SCVs, mutL was often truncated due to frameshift mutations. In conclusion, these data provide direct evidence that TD-SCVs are hypermutators. This hypermutability apparently favors the acquisition of antibiotic resistance and facilitates bacterial adaptation during long-term persistence.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Cystic Fibrosis; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Phenotype; Sequence Analysis, DNA; Staphylococcal Infections; Staphylococcus aureus; Thymidine

Since levofloxacin at high doses was more active than levofloxacin at conventional doses and was the best therapy alone in a rat model of staphylococcal foreign-body infection, in this study we tested how these differences affect the activities of their respective combinations with rifampin in vitro and in vivo. In vitro studies were performed in the log and stationary phases. By using this model, rifampin at 25 mg/kg of body weight/12 h, levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, levofloxacin at 50 mg/kg/day, levofloxacin at 50 mg/kg/day plus rifampin, or a control treatment was administered for 7 days; and therapy with for levofloxacin at 100 mg/kg/day alone and rifampin alone was prolonged to 14 days. We screened for the appearance of resistant strains. Killing curves in the log phase showed a clear antagonism with levofloxacin at concentrations >or=2x MIC and rifampin and tended to occur in the stationary phase. At the end of 7 days of therapy, levofloxacin at 100 mg/kg/day was the best treatment and decreased the bacterial counts from tissue cage fluid (P < 0.05 compared with the results for groups except those receiving rifampin alone). At the end of 14 days of therapy with levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, and the control treatment, the bacterial counts on the coverslips were 2.24 (P < 0.05 compared with the results with the combined therapy), 3.36, and 5.4 log CFU/ml, respectively. No rifampin or levofloxacin resistance was detected in any group except that receiving rifampin alone. In conclusion, high-dose levofloxacin was the best treatment and no resistant strains appeared; the addition of rifampin showed an antagonistic effect. The efficacy of the rifampin-levofloxacin combination is not significantly improved by the dosage of levofloxacin.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Dose-Response Relationship, Drug; Drug Interactions; Foreign Bodies; Levofloxacin; Male; Ofloxacin; Prosthesis-Related Infections; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Therapeutic conclusions for staphylococcal implant infections treated with debridement and implant retention can only be drawn from a small series. To this aim, data from patients with implant staphylococcal infections (1998-2006) treated with debridement and implant retention were retrospectively reviewed. Infections were defined by staphylococci isolation (two or more consecutive debridement or three sinus tract discharge samples) along with clinical criteria. Patients received oral levofloxacin plus rifampicin for >or=6 weeks after the resolution of signs/symptoms and C-reactive protein normalisation. Failure was defined as lack of response or recurrence of signs/symptoms and/or sinus tract bacterial isolation during therapy or follow-up and/or implant removal. Twenty-five patients (53.2+/-20.8 years; 48% males) were included, 12 with spinal infections and 13 with limb implant infections. Diagnosis was performed from debridement material (72%) and sinus tract discharge (28%) (11 Staphylococcus aureus and 14 coagulase-negative staphylococci (CoNS)). Time from surgery to symptom onset was higher in CoNS infections compared with S. aureus infections (21.6+/-9.3 days vs. 12.6+/-5.2 days; P=0.007). Seven patients (28%) were failures, with no differences between cured patients with respect to age, sex, infection site, time from surgery to symptom onset, sinus tract diagnosis and aetiology. Longer symptom duration prior to attendance was observed in failures (5.7+/-6.2 months vs. 1.4+/-0.6 months; P=0.04). Levofloxacin plus rifampicin showed efficacy in implant infections, which was higher for short duration of symptoms.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Coagulase; Drug Therapy, Combination; Female; Humans; Levofloxacin; Male; Middle Aged; Ofloxacin; Orthopedic Fixation Devices; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

The need to investigate novel dosing regimens and combinations is essential in combating poor treatment outcomes for Staphylococcus aureus bacteremia and endocarditis. We evaluated the impact of simulated standard- and high-dose daptomycin in combination with gentamicin or rifampin against daptomycin-susceptible and nonsusceptible matched strains of S. aureus. These strains were collected from the daptomycin bacteremia and endocarditis clinical trial and consisted of three susceptible strains (MIC, 0.25 mg/liter) and four nonsusceptible isolates (MICs, 2 to 4 mg/liter). Daptomycin regimens of 6 and 10 mg/kg of body weight daily alone and in combination with gentamicin at 5 mg/kg daily or rifampin at 300 mg every 8 h were evaluated using an in vitro model with simulated endocardial vegetations over 96 h. Rapid bactericidal activity, identified by time to 99.9% kill, was displayed in all regimens with the daptomycin-susceptible strains. Concentration-dependent activity was noted by more-rapid killing with the 10-mg/kg/day dose. The addition of gentamicin improved activity in the majority of susceptible isolates. Daptomycin 6-mg/kg/day monotherapy displayed bactericidal activity for only one of the nonsusceptible isolates and for only two isolates with increased doses of 10 mg/kg/day. Combination regimens demonstrated improvement with some but not all nonsusceptible isolates. Three isolates developed a reduction in daptomycin susceptibility with 6-mg/kg/day monotherapy, but this was suppressed with both combination therapy and high-dose daptomycin. These results suggest that high-dose daptomycin therapy and combination therapy may be reasonable treatment options for susceptible isolates; however, more investigations are needed to confirm the variability of these regimens with nonsusceptible isolates.

Topics: Anti-Bacterial Agents; Culture Media; Daptomycin; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Models, Biological; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin in combination with gentamicin, linezolid, moxifloxacin, or rifampin in time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus.

Topics: Acetamides; Anti-Bacterial Agents; Aza Compounds; Drug Synergism; Fluoroquinolones; Gentamicins; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin Resistance; Microbial Sensitivity Tests; Moxifloxacin; Oxazolidinones; Polysorbates; Quinolines; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surface-Active Agents; Vancomycin Resistance

Topics: Arthroplasty, Replacement; Biofilms; Combined Modality Therapy; Debridement; Device Removal; Diagnosis, Differential; Elbow Joint; Fractures, Ununited; Humans; Humeral Fractures; Internal Fixators; Male; Microscopy, Confocal; Middle Aged; Prosthesis Failure; Prosthesis-Related Infections; Radiography; Recurrence; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Drug Resistance, Bacterial; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

We report two pediatric patients with rifampin-induced hemolysis following treatment with low daily dose rifampin for methicillin-resistant Staphylococcus aureus (MRSA). With the increased use of rifampin to treat MRSA, physicians should be aware that patients receiving rifampin therapy are at risk for hemolysis, even at low daily doses.

Topics: Adolescent; Anemia, Hemolytic; Antibiotics, Antitubercular; Drug Therapy, Combination; Female; Hemolysis; Humans; Infant; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Endocarditis due to Abiotrophia spp. occurs in about 5% of endocarditis cases. Most of the cases respond to a combination of penicillin and gentamicin, or vancomycin. We describe a case of Staphylococcus epidermidis (CONS) and Abiotrophia spp. endocarditis that failed vancomycin treatment, but responded to daptomycin and rifampin.

Topics: Adult; Anti-Bacterial Agents; Daptomycin; Endocarditis, Bacterial; Humans; Male; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Streptococcaceae

A 4-year-old boy had surgical debulking of a cerebral astrocytoma followed by chemotherapy. He developed a subdural empyema with a teicoplanin and methicillin resistant Staphylococcus aureus. He was successfully treated with surgical drainage and 6 weeks of antibiotic therapy which included linezolid, rifampicin and metronidazole. Linezolid may be successful in treating other CNS infections caused by antibiotic resistant gram-positive organisms.

Topics: Acetamides; Anti-Infective Agents; Child, Preschool; Drainage; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Empyema, Subdural; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Staphylococcal Infections; Teicoplanin

The knowledge about efficacy of linezolid alone or in combination with rifampin in device infections is limited. We test their in vitro and in vivo efficacy in a rat model of foreign-body infection by methicillin-susceptible S. aureus.. In vitro studies for logarithmic and stationary bacteria were performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid) was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin, rifampin, linezolid-rifampin and cloxacillin-rifampin); and (ii) after 10-day therapy (groups: rifampin and linezolid-rifampin).. After 7-day therapy all groups were significantly better than controls; linezolid (Delta log cfu/ml: -0.59, no resistant strains) and cloxacillin (-0.85) were the least effective therapy; linezolid was significantly less active (P<0.05) than rifampin (-1.22, resistance 90%), cloxacillin-rifampin (-1.3) and linezolid-rifampin (-1.14). After 10-day therapy linezolid-rifampin was the most effective treatment (Delta log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective (Delta log 0.1) due to the growth of resistant strains (100%).. Linezolid alone showed moderate efficacy, whereas its combination with rifampin prevented the emergence of rifampin resistance. The efficacy of linezolid-rifampin combination was initially similar to that of rifampin alone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Drug Resistance, Bacterial; Drug Therapy, Combination; Foreign Bodies; Linezolid; Male; Microbial Sensitivity Tests; Microbial Viability; Oxazolidinones; Rats; Rifampin; Soft Tissue Infections; Staphylococcal Infections; Treatment Outcome

The main characteristics of clindamycin are adequate for treatment of osteoarticular infections (OAI): good bone diffusion, broad spectrum of antibacterial activity and oral use.. A number of 61 patients was included in an observational retrospective study of efficacy and tolerance.. Prosthetic infections accounted for 50.8% of the cases and chronic osteitis for 36.1%. The causative micro-organisms were Staphylococci (72.2%) and Streptococci (15.3%); 86.5% of these strains were susceptible to erythromycin, 9.6% were erythromycin resistant and susceptible to lincomycin. Clindamycin was associated with either ofloxacine, rifampicin, or teicoplanin in 88.5% and the average course duration was 101 days. A surgical procedure was performed in 84% of cases. Complete cure was obtained in 91.1% at 18 months of follow up. Only one cutaneous rash and one Clostridium difficile-associated diarrhea occurred. The other adverse effects were gastrointestinal in 36%, cutaneous in 6.6%, and hematological in 1.6%, but did not lead to discontinuation of therapy.. Clindamycin can be used in OAI in association with or as an alternative to rifampicin, fluoroquinolones, or glycopeptides according to microbiological data.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone Diseases; Clindamycin; Diarrhea; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Joint Diseases; Male; Middle Aged; Ofloxacin; Osteitis; Prosthesis Implantation; Retrospective Studies; Rifampin; Staphylococcal Infections; Surgical Procedures, Operative; Teicoplanin

A 64-year-old woman was admitted due to back pain and dyspnea. She was suffering from fever of unknown origin for a few weeks without aortic aneurysm by enhanced chest computed tomography (CT). Chest CT taken 1 month later revealed rupture of aortic arch aneurysm. Total arch replacement was performed with in situ grafting under selective cerebral perfusion combined with deep hypothermic circulatory arrest. Rifampicin (RFP) was sprinkled on the graft at operation and omentopexy was done 5 days after the 1st operation. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated on the culture of the aneurysmal wall, therefore, polymyxin B immobilized fiber with direct hemoperfusion (PMX-DHP) was also conducted with antibiotic therapy. Her clinical course after the 2nd operation was uneventful with no infective complication. We report a successful case of ruptured aneurysm of aortic arch infected with MRSA and review our strategy as one of feasible options without using homograft or preparative RFP-bonded vascular prosthesis.

Topics: Aneurysm, Infected; Aortic Aneurysm, Thoracic; Aortic Rupture; Blood Vessel Prosthesis Implantation; Diagnostic Imaging; Female; Humans; Intraoperative Care; Methicillin Resistance; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The primary objective of this study was to compare the efficacy of a collagen silver-coated polyester graft, InterGard, with a gelatin-sealed graft, Gelsoft, both soaked in rifampin, for resistance to direct bacterial contamination in an animal model. The second objective was to confirm the lack of inflammation from silver acetate. Vascular grafts, 6 mm in diameter, were implanted in the infrarenal aorta of 28 dogs. Intravenous cefamandole (20 mg/kg) was injected intraoperatively in all dogs. The dogs were divided into three groups. Group I included 12 dogs. Six dogs received silver grafts and six dogs received gelatin-sealed grafts, all soaked with rifampin. Grafts implanted in group I were directly infected with methicillin-resistant Staphylococcus aureus (MRSA). Group II included also six silver grafts and six gelatin-sealed grafts, all soaked with rifampin. Dogs of group II were directly infected with Escherichia coli. Group III comprised four dogs, which received gelatin unsealed grafts, directly infected with MRSA, the control group. All dogs were followed by regular clinical examination, including blood cultures. Grafts in groups I and III and in group II were harvested at 30 days and 10 days, respectively. Bacterial analyses were performed on the explanted grafts. Histology was performed on both the tissue samples and the anastomotic sites of the harvested grafts. In group I, no grafts were infected with MRSA, irrespective of graft type. In group II, no silver grafts were infected with E. coli, whereas one (16.6%) of six gelatin-sealed grafts was infected (p = 0.317). In group III, three (75%) of the four grafts were infected with MRSA. The infection rate in the silver grafts and the gelatin-sealed grafts soaked in rifampin in group I compared with the unsealed gelatin grafts in group III was statistically significantly different (p < 0.05). There was no statistically significant difference in the inflammation score, obtained by histological analysis, between rifampin-soaked silver and Gelsoft grafts in either group I or group II. There were signs of necrosis at the anastomoses in three (25%) gelsoft grafts of 12 in groups I and II. There were no clinical or biological signs of inflammation from use of silver-coated grafts. These results indicate that collagen silver-coated grafts and gelatin-sealed grafts, both soaked in rifampin, provide resistance against MRSA and E. coli. There was a trend toward better resistance but without statistical signi

Topics: Acetates; Animals; Anti-Bacterial Agents; Aorta; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Collagen; Disease Models, Animal; Dogs; Escherichia coli; Escherichia coli Infections; Gelatin; Inflammation; Methicillin-Resistant Staphylococcus aureus; Polyesters; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Silver Compounds; Staphylococcal Infections; Time Factors

Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Cross Infection; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Tuberculosis

The empiric choice of initial antibiotherapy in osteoarticular infections in infants and children must take into consideration the actual epidemiology of principal pathogens, their respective antibiotic sensitivity profile, their pharmacokinetic and pharmacodynamic properties and the results of efficacy clinical studies. After a review of recent data concerning these four major points, the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) has proposed guidelines for initial recommended schemes of antimicrobial therapy in acute and non complicated osteoarticular infections in infants and children.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bone Diseases, Infectious; Child; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Infant; Joint Diseases; Kingella kingae; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Neisseriaceae Infections; Penicillins; Pneumococcal Infections; Pristinamycin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

To test for synergy between daptomycin (DAP) and rifampin (RIF) against RIF-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolates.. Synergy testing using time-kill assay (TKA) was performed on 6 clinically, and genetically unique RIF-resistant MRSA isolates. The isolates were identified out of 489 (1.2%) samples collected during April 2003 to August 2006, from patients at the Ochsner Medical Center in New Orleans, Louisiana, United States of America.. Synergy testing of DAP plus RIF by TKA showed that 5 isolates were indifferent, but one isolate was antagonistic.. Our in vitro study failed to demonstrate synergy between DAP plus RIF, against our RIF-resistant MRSA isolates. Clinical failure of this combination should prompt the clinician to consider antagonism, as one of the potential causes.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Therapy, Combination; Humans; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Topics: Aged; Bacteremia; Catheterization, Central Venous; Chronic Disease; Daptomycin; Discitis; Humans; Jugular Veins; Male; Methicillin-Resistant Staphylococcus aureus; Pancreatitis; Rifampin; Staphylococcal Infections; Vancomycin; Virginiamycin

Topics: Acetamides; Aged, 80 and over; Anesthesia; Anti-Bacterial Agents; Bacteremia; Bone Marrow Diseases; Comorbidity; Contraindications; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Gentamicins; Hip Prosthesis; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Systemic Inflammatory Response Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Combined Modality Therapy; Daptomycin; Device Removal; Drug Therapy, Combination; Endocarditis, Bacterial; Fatal Outcome; Female; Gentamicins; Hip Prosthesis; Humans; Methicillin-Resistant Staphylococcus aureus; Mitral Valve; Postoperative Complications; Prosthesis-Related Infections; Respiratory Distress Syndrome; Rifampin; Staphylococcal Infections; Thrombocytopenia; Vancomycin

Septic arthritis following anterior cruciate ligament reconstruction is an uncommon but a serious complication resulting in six times greater hospital costs than that of uncomplicated ACL surgery and an inferior postoperative activity level. Promptly initiating a specific antibiotic therapy is the most critical treatment, followed by open or arthroscopic joint decompression, debridement and lavage. Staphylococcus lugdunensis is a coagulase-negative staphylococcus predominantly infecting the skin and soft tissue. The few reported cases of bone and joint infections by S. lugdunensis indicate that the clinical manifestations were severe, the diagnosis elusive, and the treatment difficult. If the microbiology laboratory does not use the tube coagulase (long) test to confirm the slide coagulase test result, the organism might be misidentified as Staphylococcus aureus. S. lugdunensis is more virulent than other coagulase-negative staphylococcus; in many clinical situations it behaves like S. aureus, further increasing the confusion and worsening the expected outcome. S. lugdunensis is known to cause infective endocarditis with a worse outcome, septicemia, deep tissue infection, vascular and joint prosthesis infection, osteomyelitis, discitis, breast abscess, urine tract infections, toxic shock and osteitis pubis. We present the first case report in the literature of septic arthritis with S. lugdunensis following arthroscopic ACL revision with bone-patellar-tendon-bone allograft.

Topics: Adult; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Anti-Infective Agents; Arthritis, Infectious; Arthroscopy; Bone-Patellar Tendon-Bone Grafting; Ciprofloxacin; Humans; Knee Joint; Male; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus; Surgical Wound Infection; Transplantation, Autologous

To study the feasibility and efficacy of experimental laparoscopy in the diagnosis of aortic graft infection in pigs.. Eight pigs had an aortic tube graft implanted and inoculated with either 5 x 10(4) or 10(6) CFU of Staphylococcus aureus ATCC 29213. Laparoscopy was performed after a median of 20 days with debridement and sampling for bacterial culture. Thereafter, the grafts were locally soaked in rifampicin and postoperatively, the pigs received rifampicin and ciprofloxacin orally for two weeks and were then sacrificed.. All pigs developed graft infection. One pig died from severe clostridial septicaemia before laparoscopy could be performed. The remaining pigs had all samples for bacterial culture taken by laparoscopy from the inflamed tissue. The temperature dropped significantly after laparoscopy, and no macroscopic signs of infection presented at autopsy. However, only culture from one pig was without S. aureus at autopsy.. Laparoscopy is a potential diagnostic tool for aortic graft infection and also affords the opportunity to carry out bacteriological sampling and local antibiotic treatment. The efficacy of laparoscopic treatment needs further evaluation.

Topics: Animals; Anti-Bacterial Agents; Aorta; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Ciprofloxacin; Debridement; Disease Models, Animal; Drug Therapy, Combination; Feasibility Studies; Female; Laparoscopy; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Swine; Time Factors

Infections associated with implanted biomedical devices (BAI) are predominantly caused by Staphylococcus epidermidis. We previously observed in murine experimental BAI that S. epidermidis persists in peri-implant tissue rather than on the implanted biomaterial itself (Boelens et al., J Infect Dis 2000;181:1337-1349; Broekhuizen et al., Infect Immun 2007;75:1129-1136). To investigate the efficacy of rifampicin/vancomycin to clear S. epidermidis from implants and peri-implant tissues, mice with two implants were challenged with 10(7) cfu S. epidermidis per implant and received daily injections of rifampicin (25 mg/kg) and vancomycin (50 mg/kg). On the day of termination, implants and peri-implant tissue were collected and processed for culture and histology. After 1 and 8 days, implants of control mice were culture positive in 14/18 and 5/16 cases, respectively, and tissue biopsies were all culture positive. In the antibiotic-treated mice, bacteria were recovered from only 1/18 and 1/16 implants after 1 and 8 days, respectively, whereas the tissues were culture positive in 14/18 and 7/16 biopsies, respectively. In microscopy, bacteria were seen in the tissue at a distance of several cell layers from the tissue-implant interface, colocalized with host cells. Thus, although a regimen of rifampicin/vancomycin sterilized the implants, S. epidermidis persisted in peri-implant tissue, which might be an as yet unrecognized reservoir in the pathogenesis of BAI.

Topics: Animals; Anti-Bacterial Agents; Biopsy; Colony Count, Microbial; Female; Mice; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Time Factors; Treatment Failure; Vancomycin

We compared the efficacy of quinupristin/dalfopristin versus vancomycin, alone or in combination with rifampicin, in a rabbit model of methicillin-resistant Staphylococcus aureus-induced arthritis. Vancomycin, alone or in combination with rifampicin, and quinupristin/dalfopristin+rifampicin were significantly more effective than quinupristin/dalfopristin alone.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Disease Models, Animal; Drug Therapy, Combination; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Virginiamycin

An elderly patient with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was treated sequentially with vancomycin plus rifampin then daptomycin plus gentamicin. The MRSA strain developed diminished susceptibility to vancomycin (MIC increase and tolerance), daptomycin, and gentamicin, and resistance to rifampin during therapy.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Daptomycin; Female; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin.. A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically.. The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone.. A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Linezolid; Male; Mediastinitis; Methicillin Resistance; Oxazolidinones; Rats; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

Topics: Administration, Intranasal; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Carrier State; Chlorhexidine; Doxycycline; Humans; Iodine; Methicillin Resistance; Mupirocin; Nasal Mucosa; Orthopedic Procedures; Preoperative Care; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

Topics: Anti-Bacterial Agents; Bacteremia; Humans; Infant, Newborn; Infant, Premature, Diseases; Infusions, Intravenous; Male; Nucleic Acid Synthesis Inhibitors; Rifampin; Staphylococcal Infections; Vancomycin

To evaluate the efficacy of oral linezolid, with or without rifampicin, on valve vegetations and secondary foci of infection compared with vancomycin, in the absence or presence of rifampicin, in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.. Treatment groups were controls (n = 16), linezolid (n = 15), vancomycin (n = 15), linezolid and rifampicin (n = 15), vancomycin and rifampicin (n = 13), linezolid relapse (n = 11) and vancomycin relapse (n = 9). Therapy lasted 5 days in all groups, with survival of animals in the linezolid relapse and vancomycin relapse groups being recorded for an additional 5 days. Blood was drawn to determine the linezolid concentration, and valve vegetations, and kidney, liver, lung and spleen segments were collected for culture.. Survival in each individual group was higher than that in the control group; bacterial load in valve vegetations was reduced by all treatment regimens, with linezolid exhibiting bactericidal effects. Bactericidal activity of linezolid was noted in all secondary foci of infection except the lung, where only the combination of rifampicin with linezolid was bactericidal.. Orally administered linezolid is effective in limiting bacterial growth in the secondary foci of endocarditis. Co-administration of rifampicin favoured the suppression of bacterial growth in the lung.

Topics: Acetamides; Administration, Oral; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valves; Kidney; Linezolid; Liver; Lung; Male; Methicillin Resistance; Microbial Sensitivity Tests; Microbial Viability; Models, Animal; Oxazolidinones; Plasma; Rabbits; Rifampin; Spleen; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis; Vancomycin

Staphylococcus aureus is a common cause of native valve infective endocarditis (IE). Rifampin is often added to traditional therapy for the management of serious S. aureus infections. There are no large, prospective studies documenting the safety and efficacy of adjunctive therapy with rifampin for treatment of native valve S. aureus IE. We reviewed all cases of definite native valve S. aureus IE confirmed by modified Duke criteria in a large urban hospital between 1 January 2004 and 31 December 2005. A retrospective cohort analysis was used to assess the impact of the addition of rifampin to standard therapy. There were 42 cases of S. aureus IE treated with the addition of rifampin and 42 controls. Cases received a median of 20 days of rifampin (range, 14 to 48 days). Rifampin-resistant S. aureus isolates developed in nine cases who received rifampin before clearance of bacteremia (56%), while significant hepatic transaminase elevations also occurred in nine cases, all of whom had hepatitis C infection. Unrecognized significant drug-drug interactions with rifampin occurred frequently (52%). Cases were more likely to have a longer duration of bacteremia (5.2 versus 2.1 days; P < 0.001) and were less likely to survive (79% versus 95%; P = 0.048) than controls. Our results suggest that the potential for hepatotoxicity, drug-drug interactions, and the emergence of resistant S. aureus isolates warrants a careful risk-benefit assessment before adding rifampin to standard antibiotic treatment of native valve S. aureus IE until further clinical studies are performed.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Drug Interactions; Drug Resistance, Bacterial; Endocarditis, Bacterial; Female; Heart Valve Diseases; Humans; Liver; Male; Middle Aged; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI) have become increasingly common. This study's objectives were to describe the clinical spectrum of MRSA in a community health center and to determine whether the use of specific antimicrobials correlated with increased probability of clinical resolution of SSTI. A retrospective chart review of 399 sequential cases of culture-confirmed S. aureus SSTI, including 227 cases of MRSA SSTI, among outpatients at Fenway Community Health (Boston, MA) from 1998 to 2005 was done. The proportion of S. aureus SSTI due to MRSA increased significantly from 1998 to 2005 (P<0.0001). Resistance to clindamycin was common (48.2% of isolates). At the beginning of the study period, most patients with MRSA SSTI empirically treated with antibiotics received a beta-lactam, whereas by 2005, 76% received trimethoprim-sulfamethoxazole (TMP-SMX) (P<0.0001). Initially, few MRSA isolates were sensitive to the empirical antibiotic, but 77% were susceptible by 2005 (P<0.0001). A significantly higher percentage of patients with MRSA isolates had clinical resolution on the empirical antibiotic by 2005 (P=0.037). Use of an empirical antibiotic to which the clinical isolate was sensitive was associated with increased odds of clinical resolution on empirical therapy (odds ratio=5.91), controlling for incision and drainage and HIV status. MRSA now accounts for the majority of SSTI due to S. aureus at Fenway, and improved rates of clinical resolution on empirical antibiotic therapy have paralleled increasing use of empirical TMP-SMX for these infections. TMP-SMX appears to be an appropriate empirical antibiotic for suspected MRSA SSTI, especially where clindamycin resistance is common.

Topics: Adult; Ambulatory Care Facilities; Anti-Bacterial Agents; Boston; Female; HIV Infections; Humans; Male; Methicillin Resistance; Middle Aged; Soft Tissue Infections; Staphylococcal Infections; Staphylococcal Skin Infections; Staphylococcus aureus; Treatment Outcome

Staphylococcus lugdunensis is an atypically virulent coagulase-negative staphylococcal species associated with acute and destructive infections that often resemble Staphylococcus aureus infections. Several types of infection caused by S. lugdunensis (e.g., native valve endocarditis, prosthetic joint infection, and intravascular catheter infection) are associated with biofilm formation, which may lead to an inability to eradicate the infection due to the intrinsic nature of biofilms to resist high levels of antibiotics. In this study, planktonic MICs and MBCs and biofilm bactericidal concentrations of 10 antistaphylococcal antimicrobial agents were measured for 15 S. lugdunensis isolates collected from patients with endocarditis, medical device infections, or skin and soft tissue infections. Planktonic isolates were susceptible to all agents studied, but biofilms were resistant to high concentrations of most of the drugs. However, moxifloxacin was able to kill 73% of isolates growing in biofilms at

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biofilms; DNA, Bacterial; Humans; Linezolid; Microbial Sensitivity Tests; Nafcillin; Oxazolidinones; Penicillin-Binding Proteins; Penicillins; Reverse Transcriptase Polymerase Chain Reaction; Staphylococcal Infections; Staphylococcus; Tetracycline

We compared the efficacy of a novel rifamycin derivative, ABI-0043, with that of rifampin, alone and in combination with levofloxacin, against methicillin-susceptible Staphylococcus aureus ATCC 29213 in a guinea pig tissue-cage infection model. The MIC, logarithmic-growth-phase minimal bactericidal concentration, and stationary-growth-phase minimal bactericidal concentration of ABI-0043 were 0.001, 0.008, and 0.25 microg/ml, respectively; the corresponding concentrations of rifampin were 0.016, 0.8, and 3.6 microg/ml, respectively. After a single intraperitoneal dose of 12.5 mg/kg of body weight, the peak concentration in cage fluid was 1.13 micarog/ml of ABI-0043 and 0.98 microg/ml of rifampin. Five days after completion of treatment, levofloxacin administered alone (5 mg/kg/12 h) resulted in bacterial counts in cage fluid that were similar to those for untreated controls (>8.0 log(10) CFU/ml), whereas rifampin and ABI-0043 administered alone (12.5 mg/kg/12 h) decreased the mean titers of bacteria +/- standard deviations to 1.43 +/- 0.28 log(10) and 1.57 +/- 0.53 log(10) CFU/ml, respectively, in cage fluid. In combination with levofloxacin, both rifamycins cleared bacteria from the cage fluid. The cure rates of cage-associated infections with rifampin and ABI-0043 administered alone were 46% and 58%, respectively, and increased to 88% and 92% in combination with levofloxacin. Emergence of rifamycin resistance was observed in 42% of cages after ABI-0043 therapy and in 38% of cages after rifampin therapy; no emergence of resistance occurred with combination treatment with levofloxacin. In conclusion, ABI-0043 had cure rates comparable to that of rifampin. ABI-0043 in combination with a quinolone has the potential for treatment of implant-associated infections caused by susceptible strains of S. aureus, potentially without drug-drug interactions.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Foreign-Body Reaction; Guinea Pigs; Injections, Intraperitoneal; Levofloxacin; Male; Microbial Sensitivity Tests; Molecular Structure; Ofloxacin; Rifampin; Rifamycins; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Current treatment for serious infections caused by methicillin-resistant Staphylococcus aureus relies heavily upon the glycopeptide antibiotic vancomycin. Unfortunately, this practice has led to an intermediate resistance phenotype that is particularly difficult to treat in invasive staphylococcal diseases, such as septicemia and its metastatic complications, including endocarditis. Although the vancomycin-intermediate resistance phenotype has been linked to abnormal cell wall structures and autolytic rates, the corresponding genetic changes have not been fully elucidated. Previously, whole-genome array studies listed numerous genes that are overexpressed in vancomycin-intermediate sensitive strains, including graRS (SACOL0716 to -0717), encoding a two-component regulatory system (TCRS), as well as the adjacent vraFG (SACOL0718 to -0720), encoding an ATP-binding cassette (ABC) transporter; but the exact contribution of these genes to increased vancomycin resistance has not been defined. In this study, we showed that isogenic strains with mutations in genes encoding the GraRS TCRS and the VraFG ABC transporter are hypersensitive to vancomycin as well as polymyxin B. Moreover, GraRS regulates the expression of the adjacent VraFG pump, reminiscent of gram-positive bacteriocin-immunity regulons. Mutations of graRS and vraFG also led to increased autolytic rates and a more negative net surface charge, which may explain, in part, to their increased sensitivity to cationic antimicrobial peptides. Taken together, these data reveal an important genetic mediator to the vancomycin-intermediate S. aureus phenotype and may hold clues to the selective pressures on staphylococci upon exposure to selective cationic peptide antibiotics used in clinical practice.

Topics: Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Polymyxin B; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Vancomycin Resistance

Topics: Antibiotics, Antitubercular; Antifungal Agents; Area Under Curve; Communication; Drug Interactions; Humans; Leukemia, Myeloid; Medication Errors; Pyrimidines; Rifampin; Staphylococcal Infections; Triazoles; Voriconazole

Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMup(r)) were compared with those of mupirocin-susceptible (Mup(s)) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMup(r) MRSA isolates were identified. The proportion of MRSA strains with HLMup(r) increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMup(r) MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMup(r) MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMup(r) MRSA strains had a plasmid-associated mupA gene, most often associated with a 9-kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMup(r) MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMup(r) is increasing among Canadian strains of MRSA and that HLMup(r) MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mup(s) MRSA strains.

Topics: Aged; Anti-Bacterial Agents; Canada; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Mupirocin; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Cefoperazone; Drug Therapy, Combination; Fosfomycin; Fusidic Acid; Humans; Male; Methicillin Resistance; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulbactam

Only 3 cases of infective endocarditis (IE) due to methicillin-resistant Staphylococcus haemolyticus (MRSH) have been reported in English literature. Here we report 4 cases of IE due to MRSH encountered in a single university hospital. Population analysis of the strains was performed to assess the presence of vancomycin/teicoplanin heteroresistant subpopulations. Pulsed-field gel electrophoresis was used for molecular typing of isolates. IE was defined in 3 cases as health care associated, and in 1 case, as community acquired. A causative strain was lost. Two strains were heteroresistant to teicoplanin, and 1 also to vancomycin. Genome macrorestriction profile studies demonstrated that 2 MRSH isolates belonged to clones A and E, possessing a class C1 mecDNA, whereas 1 clone was sporadic. All patients were treated with vancomycin plus rifampin. Two patients were cured with antibiotic therapy alone, 1 patient needed surgery, and 1 patient died. Methicillin-resistant multiresistant S. haemolyticus may represent a difficult-to-treat cause of both community and nosocomially acquired IE.

Topics: Aged; Anti-Bacterial Agents; Aortic Valve; Bacteremia; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Endocarditis, Bacterial; Female; Humans; Male; Methicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus haemolyticus; Vancomycin

The adequate treatment of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis has intrigued clinicians for some time. As the resistance of these pathogens, coupled with the increase in community-acquired cases, continues steadily to rise, clinicians are finding it useful to employ multi-modal approaches for efficacious treatment. The authors present a single case report of a patient with recurrent MRSA osteomyelitis, lumbar paraspinal and epidural abscess. He was found to have decreased muscle strength and was hyporeflexic in the involved extremity. Serum testing demonstrated MRSA bacteremia. Neuroimaging studies revealed evidence of paraspinal abscess and a presumed herniated nucleus pulposus at the L5/S1 interspace with significant nerve root compromise. Despite antimicrobials, his symptoms persisted, necessitating surgical exploration. At surgery, paraspinal and epidural abscesses were encountered and debrided; however, no herniated disc was visualized. This case demonstrates the diagnostic and therapeutic dilemmas with which these lesions present. We postulate that the MRSA osteomyelitis/discitis pathogens were walled off in the disc space and subsequently inoculated the soft tissues with ensuing bacteremia. We concur that antimicrobial treatment should be the first line of therapy for these patients; however, surgical debridements and cautious spinal instrumentation should be employed where appropriate.

Topics: Abscess; Acetamides; Adult; Anti-Bacterial Agents; Bacteremia; Debridement; Drug Therapy, Combination; Humans; Intervertebral Disc Displacement; Laminectomy; Linezolid; Lumbar Vertebrae; Male; Methicillin Resistance; Osteomyelitis; Oxazolidinones; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Treatment Outcome; Vancomycin

We hypothesized that regimens with an early switch to oral antibiotics are as effective as prolonged parenteral regimens for staphylococcal osteomyelitis.. We retrospectively reviewed records of adult patients with osteomyelitis caused by Staphylococcus aureus as determined by sterile site cultures, who had at least 6 months of follow-up post-therapy. The population was divided into two treatment groups: (1) an intravenous group (i.v.) that received > or = 4 weeks of parenteral therapy, and (2) a switch group that received < 4 weeks of intravenous followed by oral therapy.. A total of 72 patients (36 in each group) were identified with groups evenly matched for demographic and clinical characteristics. The overall apparent cure rate was 74%; 69% for the i.v. group and 78% for the switch group (P=0.59). Apparent cure rates were similar regardless of duration of intravenous therapy: 83% < 2 weeks, 72% 2-4 weeks, 75% 4-6 weeks and 66% > or = 6 weeks (P=0.68). Among the 39 patients who received rifampin-based combinations, those treated simultaneously with vancomycin and rifampin did significantly worse than those who received other rifampin combinations (P<0.02). Overall, MRSA infections responded poorly compared to MSSA (65% apparently cured versus 83%). However, 11/14 (79%) MRSA patients who received rifampin combinations, other than vancomycin and rifampin simultaneously, were apparently cured.. Overall outcomes did not differ significantly between i.v. and switch groups. Given the markedly lower costs and ease of administration, prolonged oral regimens after initial intravenous therapy may be a preferred regimen for staphylococcal osteomyelitis.

Topics: Administration, Oral; Anti-Bacterial Agents; Cohort Studies; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Methicillin Resistance; Middle Aged; Osteomyelitis; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Shunt infection is a common and serious complication of cerebrospinal fluid (CSF) shunting most commonly caused by skin flora contamination at surgery. Recent studies indicate that the use of antibiotic-impregnated (AI) shunt systems may reduce the risk of postoperative shunt infections. We evaluated the incidence of shunt infections associated with the use of AI shunt catheters and compared it with the incidence associated with standard non-AI catheters.. All shunt procedures performed by one surgeon using AI catheters were reviewed. An equal number of consecutive shunt procedures performed by the same surgeon using non-AI catheters were reviewed from the period immediately before the introduction of the AI system. Patients with <9 months of follow-up were excluded; all shunt infections and shunt-related complications were recorded. The proportions of infected shunts in the AI and control groups were compared using a chi (2) analysis.. We reviewed 160 shunt procedures (80 per group). The infection rate was 5.0% among patients with AI catheters compared with 8.8% in the control group (P = 0.534, Fischer's exact). The average time to infection was similar between the two groups. Among the AI group, the shunt infection rate did not differ between ventricular catheter, distal catheter revisions, and revisions of ventricular and peritoneal tubing. In contrast with other reports, we found no significant reduction in the pediatric CSF shunt infection rate with the use of AI shunt systems. Any recommendation for or against the routine use of AI systems in children requires a prospective, blinded, randomized-controlled trial with adequate power.

Topics: Adolescent; Anti-Bacterial Agents; Catheters, Indwelling; Cerebrospinal Fluid Shunts; Chi-Square Distribution; Child; Child, Preschool; Clindamycin; Cohort Studies; Female; Humans; Infant; Male; Postoperative Complications; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Treatment Outcome

In this report we describe the in vivo antibacterial activity of linezolid in an experimental graft infection model in rats and compare it with teicoplanin. The objective of this study was also to determine the effects of the interaction of linezolid when it was combined with rifampicin and test this effect against strains of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.. Graft infections were established in the subcutaneous tissue of 130 Wistar rats by implantation of Dacron grafts followed by a topical inoculation with 2 x 10(7) CFU of clinical isolates of MRSA and MRSE. The study included a control group and six groups for each of the staphylococcal strains: an inoculated group that did not receive any antibiotic prophylaxis, two inoculated groups that received intraperitoneal prophylaxis with teicoplanin or linezolid alone, an inoculated group that received rifampicin-soaked grafts, and two inoculated groups that received a combination prophylaxis consisting of intraperitoneal teicoplanin or linezolid and rifampicin-soaked grafts.. There was a reduction in the quantitative bacterial graft cultures in all prophylaxis groups when compared with inoculated control groups. There was not a statistically significant difference between linezolid and teicoplanin prophylaxis groups. The best results were obtained by a combination of rifampicin-soaked grafts with linezolid or teicoplanin.. We found no evidence to suggest that linezolid differs from teicoplanin regarding effectiveness in the prevention of prosthetic vascular graft infection. Linezolid plus rifampicin and teicoplanin plus rifampicin are demonstrated to be valuable prophylactic regimens.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Blood Vessel Prosthesis; Drug Synergism; Linezolid; Male; Methicillin Resistance; Oxazolidinones; Prosthesis-Related Infections; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin

Serious gram-positive infections present an increasingly common therapeutic dilemma. Combination antimicrobial regimens (e.g., linezolid with rifampin) aimed at improving bacterial eradication and preventing resistance are often used; however, most data supporting this treatment strategy are not from randomized controlled trials. We describe a patient with disseminated community-acquired methicillin-resistant Staphylococcus aureus infection who experienced a possible drug interaction between linezolid and rifampin that resulted in decreased serum linezolid levels. To our knowledge, this is the first published report of a possible drug interaction in a critically ill patient receiving concomitant linezolid and rifampin. Although we hypothesize that the reaction was caused by P-glycoprotein expression, further study is warranted.

Topics: Acetamides; Adult; Anti-Infective Agents; Critical Care; Drug Interactions; Female; Humans; Linezolid; Methicillin Resistance; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus

There is growing evidence of the efficacy of treating early staphylococcal infections of prosthetic joints with surgical debridement and prosthesis retention, combined with oral antibiotic regimens that include rifampicin in combination with a fluoroquinolone. With rising rates of fluoroquinolone-resistant staphylococci, evidence concerning the efficacy of alternative combinations of antibiotics is required. Twenty patients with staphylococcal prosthetic joint infections who had been treated with surgical debridement and prosthesis retention, and a combination of rifampicin and fusidic acid were analysed. The mean duration of symptoms before initial debridement was 16 (range 2-75) days. The median time of follow-up was 32 (range 6-76) months. Treatment failure occurred in two patients. The cumulative risk of treatment failure after 1 year was 11.76% (95% CI 3.08-39.40%). Two patients had their treatment changed because of nausea. Ten of 11 patients with infections involving methicillin-resistant Staphylococcus aureus had successful outcomes. Debridement without prosthesis removal, in combination with rifampicin and fusidic acid treatment, was effective and should be considered for patients with early staphylococcal prosthetic joint infections, including those with infections involving fluoroquinolone-resistant organisms.

Topics: Administration, Oral; Aged; Aged, 80 and over; Debridement; Device Removal; Female; Fusidic Acid; Humans; Joint Prosthesis; Male; Middle Aged; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Treatment Outcome

Topics: Aminoglycosides; beta-Lactams; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Male; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Sensitivity and Specificity; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Since device colonization is a prelude to infection, an antimicrobial-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis.. Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits.. The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit.. Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model.. It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans.

Topics: Animals; Anti-Infective Agents; Drug Delivery Systems; Minocycline; Osteomyelitis; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections

The spread of multidrug-resistant Staphylococcus aureus (MRSA) strains in the clinical environment has begun to pose serious limits to treatment options. Yet virtually nothing is known about how resistance traits are acquired in vivo. Here, we apply the power of whole-genome sequencing to identify steps in the evolution of multidrug resistance in isogenic S. aureus isolates recovered periodically from the bloodstream of a patient undergoing chemotherapy with vancomycin and other antibiotics. After extensive therapy, the bacterium developed resistance, and treatment failed. Sequencing the first vancomycin susceptible isolate and the last vancomycin nonsusceptible isolate identified genome wide only 35 point mutations in 31 loci. These mutations appeared in a sequential order in isolates that were recovered at intermittent times during chemotherapy in parallel with increasing levels of resistance. The vancomycin nonsusceptible isolates also showed a 100-fold decrease in susceptibility to daptomycin, although this antibiotic was not used in the therapy. One of the mutated loci associated with decreasing vancomycin susceptibility (the vraR operon) was found to also carry mutations in six additional vancomycin nonsusceptible S. aureus isolates belonging to different genetic backgrounds and recovered from different geographic sites. As costs drop, whole-genome sequencing will become a useful tool in elucidating complex pathways of in vivo evolution in bacterial pathogens.

Topics: Anti-Bacterial Agents; Base Sequence; beta-Lactam Resistance; Biological Evolution; Drug Resistance, Multiple; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genome, Bacterial; Humans; Mutation; Phenotype; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Abscess; Adult; Anti-Bacterial Agents; Cloxacillin; Endocarditis, Bacterial; Fever; Humans; Levofloxacin; Male; Methicillin Resistance; Ofloxacin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tricuspid Valve

This study was designed to investigate the role of hypermutability of Staphylococcus aureus on bacterial fitness and antibiotic resistance in a model of chronic bone infection. An isogenic pair of strains, S. aureus RN4220 and its mutator counterpart inactivated in the mutL gene were used in a rat model of osteomyelitis of the tibia. The effect of the mutator phenotype in the emergence of antibiotic resistance was assessed in rats infected by each strain separately and treated with rifampicin for 5 days. No difference between the two strains was found in bacterial growth in vitro and in bacterial survival in the animal model, indicating no fitness defect in the mutator strain. In competition studies performed in rats coinfected with the two strains at a same ratio and sacrificed at different times from day 3 to day 42 postinoculation, the mutator strain was clearly disadvantaged because it was found in all rats and at all study times at lower counts (P<0.05 from day 14 to day 42). Two of the 16 rats infected by the mutator strain and none of the 14 rats infected by the wild-type strain had acquired rifampicin-resistant mutants (P=0.4). Data suggest that the S. aureus mutator phenotype was associated with a decreased bacterial fitness in vivo and did not confer significant advantage in the acquisition of antibiotic resistance in a model of chronic bone infection.

Topics: Adenosine Triphosphatases; Animals; Bacterial Proteins; Bone and Bones; Colony Count, Microbial; Drug Resistance, Bacterial; Gene Deletion; Microbial Sensitivity Tests; Mutagenesis, Insertional; Osteomyelitis; Rats; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Survival Analysis

The aim of this study was to evaluate the efficacy of a new gelatin-sealed graft prebonded with two antibiotics in resisting infection with Staphylococcus aureus (S aureus) A980142 after direct bacterial application in a dog model.. Twelve 6.0-mm polyester grafts were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into two groups. A test group (n = 6) received experimental antibiotic-bonded gelatin-sealed knitted polyester grafts, loaded with two antibiotics, rifampin and tobramycin. A control group (n = 6) received commercial gelatin-sealed knitted polyester grafts. At the end of graft implantation, 50 mul of a 1.8 x 10(4) CFU/mL S aureus solution were instilled directly over the graft. One week after implantation, grafts were harvested with sterile technique. Quantitative cultures were obtained from all the harvested grafts. The results were expressed as colony-forming units per cm(2) of surface of the graft. Bacteriological study was also performed on various tissue samples. The chi(2) test was used to compare the culture proven infection of control and antibiotics-bonded grafts.. Mean inoculum size was similar in the two groups of dogs. Five of the six control grafts grew S aureus A980142 at the time of graft removal, whereas none of the six antibiotic-bonded gelatin-sealed grafts were infected (P = .0192). None of the organ samples were infected in the group implanted with antibiotic-bonded grafts, whereas 15/34 samples grew S. aureus in the control group.. These results indicate that this gelatin sealed graft prebonded with two antibiotics resists infection caused by S aureus graft contamination in a dog model.

Topics: Animals; Antibiotics, Antitubercular; Aorta, Abdominal; Blood Vessel Prosthesis; Dogs; Female; Gelatin; Male; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tobramycin

Topics: Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Dexamethasone; Floxacillin; Gentamicins; Humans; Magnetic Resonance Imaging; Male; Meningitis, Bacterial; Methylprednisolone; Rifampin; Staphylococcal Infections; Vasculitis

An in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms developed on 96-well polystyrene tissue culture plates was performed to elucidate the activity of citropin 1.1, rifampin and minocycline. Efficacy studies were performed in a rat model of staphylococcal CVC infection. Silastic catheters were implanted into the superior cava. Twenty-four hours after implantation the catheters were filled with citropin 1.1 (10 microg/mL). Thirty minutes later the rats were challenged via the CVC with 1.0 x 10(6) CFU of S. aureus strain Smith diffuse. Administration of antibiotics into the CVC (the antibiotic lock technique) began 24 h later. The study included: one control group (no CVC infection), one contaminated group that did not receive any antibiotic prophylaxis, one contaminated group that received citropin 1.1-treated CVC, two contaminated groups that received citropin 1.1-treated CVC plus rifampin and minocycline at concentrations equal to MBCs for adherent cells and 1024 microg/mL in a volume of 0.1 mL that filled the CVC and two contaminated groups that received rifampin or minocycline at the same concentrations. All catheters were explanted 7 days after implantation. Main outcome measures were: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), synergy studies, quantitative culture of the biofilm formed on the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. MICs of conventional antibiotics against the bacteria in a biofilm were at least four-fold higher than against the freely growing planktonic cells. In contrast, when antibiotics were used on citropin 1.1 pre-treated cells they showed comparable activity against both biofilm and planktonic organisms. The in vivo studies show that when CVCs were pre-treated with citropin 1.1 or with a high dose of antibiotics, biofilm bacterial load was reduced from 10(7) to 10(3) CFU/mL and bacteremia reduced from 10(3) to 10(1) CFU/mL. When CVCs were treated both with citropin 1.1 and antibiotics, biofilm bacterial load was further reduced to 10(1) CFU/mL and bacteremia was not detected, suggesting 100% elimination of bacteremia and a log 6 reduction in biofilm load. Citropin 1.1 significantly reduces bacterial load and enhances the effect of hydrophobic antibiotics in the treatment of CVC-associated S. aureus infections.

Topics: Amphibian Proteins; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Biofilms; Catheterization; Catheterization, Central Venous; Male; Microbial Sensitivity Tests; Minocycline; Polystyrenes; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Treatment Outcome

Topics: Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Genotype; Humans; Intensive Care Units; Methicillin Resistance; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Standardized susceptibility testing fails to predict in vivo resistance of device-related infections to antimicrobials. We assessed agents and combinations of antimicrobials against clinical isolates of Staphylococcus epidermidis and S. aureus (methicillin-resistant S. aureus and methicillin-sensitive S. aureus) retrieved from device-associated infections. Isolates were grown planktonically and as biofilms. Biofilm cultures of the organisms were found to be much more resistant to inhibitory and bactericidal effects of single and combination antibiotics than planktonic cultures (P < 0.001). Rifampin was the most common constituent of antibiotic combinations active against staphylococcal biofilms. Other frequently effective antimicrobials were vancomycin and fusidic acid. Susceptibility testing involving biofilm-associated bacteria suggests new options for combination antibiotic therapy.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusidic Acid; Methicillin Resistance; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

The adaptive and further evolutionary responses of Staphylococcus aureus to selection pressure with the antibiotic rifampin have not been explored in detail. We now present a detailed analysis of these systems. The use of rifampin for the chemotherapy of infections caused by S. aureus has resulted in the selection of mutants with alterations within the beta subunit of the target enzyme, RNA polymerase. Using a new collection of strains, we have identified numerous novel mutations in the beta subunits of both clinical and in vitro-derived resistant strains and established that additional, undefined mechanisms contribute to expression of rifampin resistance in clinical isolates of S. aureus. The fitness costs associated with rifampin resistance genotypes were found to have a significant influence on their clinical prevalence, with the most common clinical genotype (H481N, S529L) exhibiting no fitness cost in vitro. Intragenic mutations which compensate for the fitness costs associated with rifampin resistance in clinical strains of S. aureus were identified for the first time. Structural explanations for rifampin resistance and the loss of fitness were obtained by molecular modeling of mutated RNA polymerase enzymes.

Topics: DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Humans; Models, Molecular; Mutation; Prevalence; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Staphylococcus aureus is responsible for 80% of human osteomyelitis. It can invade and persist within osteoblasts. Antibiotic resistant strains of S. aureus make successful treatment of osteomyelitis difficult.. antibiotic sensitivities of S. aureus do not change after exposure to the osteoblast intracellular environment. Human and mouse osteoblast cultures were infected and S. aureus cells were allowed to invade. Following times 0, 12, 24, and 48 h ( +/- the addition of erythromycin, clindamycin, and rifampin at times 0 or 12 h), the osteoblasts were lysed and intracellular bacteria enumerated. Transmission electron microscopy was performed on extracellular and intracellular S. aureus cells. In mouse osteoblasts, administration of bacteriostatic antibiotics at time 0 prevented the increase in intracellular S. aureus. If the antibiotics were delayed 12 h, this did not occur. When rifampin (bactericidal) was introduced at time 0 to human and mouse osteoblasts, there was a significant decrease in number of intracellular S. aureus within osteoblasts compared to control. If rifampin was delayed 12 h, this did not occur. Significant time-dependent S. aureus structural changes were observed after exposure to the osteoblast intracellular environment. These studies demonstrate that once S. aureus is established intracellularly for 12 h, the bacteria are less sensitive to antibiotics capable of eukaryotic cell penetration (statistically significant). These antibiotic sensitivity changes could be due in part to the observed structural changes. This leads to the rejection of our null hypotheses that the antibiotic sensitivities of S. aureus are unaltered by their location.

Topics: Animals; Cells, Cultured; Drug Resistance, Bacterial; Erythromycin; Gentamicins; Humans; Mice; Microscopy, Electron, Transmission; Osteoblasts; Osteomyelitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Topics: Acetamides; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Humans; Linezolid; Meningitis, Bacterial; Methicillin Resistance; Middle Aged; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Outcome; Vancomycin

Topics: Administration, Oral; Adolescent; Aged; Anti-Bacterial Agents; Clindamycin; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Femur; Fusidic Acid; Hip Prosthesis; Humans; Male; Methicillin Resistance; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

We describe novel rifamycin derivatives (new chemical entities [NCEs]) that retain significant activity against a comprehensive collection of Staphylococcus aureus strains that are resistant to rifamycins. This collection of resistant strains contains 21 of the 26 known single-amino-acid alterations in RpoB, the target of rifamycins. Some NCEs also demonstrated a lower frequency of resistance development than rifampin and rifalazil in S. aureus as measured in a resistance emergence test. When assayed for activity against the strongest rifamycin-resistant mutants, several NCEs had MICs of 2 microg/ml, in contrast to MICs of rifampin and rifalazil, which were 512 microg/ml for the same strains. The properties of these NCEs therefore demonstrate a significant improvement over those of earlier rifamycins, which have been limited primarily to combination therapy due to resistance development, and suggest a potential use of these NCEs for monotherapy in several clinical indications.

Topics: Drug Resistance, Bacterial; In Vitro Techniques; Molecular Conformation; Rifabutin; Rifampin; Rifamycins; Staphylococcal Infections; Staphylococcus aureus

To assess whether the occurrence of rifampicin (RFP) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is related to treatment of tuberculosis, we determined the RFP susceptibility of MRSA isolates obtained from tuberculosis patients and screened for mutation(s) in the rpoB gene of these isolates. The MICs of RFP for 84 MRSA isolates obtained from two hospitals in Japan were determined. DNA was sequenced in the region 1318-1602 nucleotides (nt) of the rpoB gene, which includes RFP resistance-determining clusters I (1384-1464 nt, 462-488 amino acids). The majority of MRSA isolates from tuberculosis wards, i.e., 48 of 51 (94%) [33 of 34 in a Tokyo hospital (97%) and 15 of 17 in a Chubu hospital (88%)], were resistant to RFP. Meanwhile, no isolates of 33 from the other wards were resistant to RFP. All RFP-resistant MRSA isolates had a mutation(s), including novel mutation(s) such as Val453-->AEPhe, Asp471-->AEAsn, and Ile527-->AELeu, in rpoB. An emergence of RFP-resistant MRSAs in tuberculosis wards in Japan was strongly suggested.

Topics: Amino Acid Sequence; Antibiotics, Antitubercular; Base Sequence; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled.. We studied mitochondrial ultrastructure, mitochondrial respiratory chain enzyme activity, and mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic acidosis, and renal failure after prolonged use of linezolid. In addition, we evaluated mtDNA, respiratory chain enzyme activity, and protein amount in muscle and liver samples obtained from experimental animals that received linezolid or placebo.. In the patient, mitochondrial respiratory chain enzyme activity was decreased in affected tissues, without ultrastructural mitochondrial abnormalities and without mutations or depletion of mtDNA. In the experimental animals, linezolid induced a dose- and time-dependent decrease of the activity of respiratory chain complexes containing mtDNA-encoded subunits and a decreased amount of protein of these complexes, whereas the amount of mtDNA was normal.. These results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences. Prolonged courses of linezolid should be avoided if alternative treatment options are available.

Topics: Acetamides; Animals; Anti-Infective Agents; DNA, Mitochondrial; Drug Therapy, Combination; Female; Humans; Kidney; Linezolid; Male; Middle Aged; Mitochondria; Mitochondria, Liver; Mitochondria, Muscle; Oxazolidinones; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Rifampin; Staphylococcal Infections

Methicillin-resistant Staphylococcus aureus (MRSA) infections are commonly treated with vancomycin (VAN) or another glycopeptide antibiotic. However, when vancomycin fails or infections recur, there are few other therapeutic options. Presented here are 2 cases where a novel combination of daptomycin, vancomycin, and rifampin resolved recurrent MRSA bone and prosthetic joint functions.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Therapy, Combination; Female; Humans; Joint Prosthesis; Male; Methicillin Resistance; Middle Aged; Postoperative Period; Rifampin; Staphylococcal Infections; Vancomycin

A premature twin of 1.9 kg had mitral valve endocarditis develop during neonatal intensive care. Vegetation involving the entire anterior mitral valve leaflet was identified. Reconstruction was achieved by near complete resection of the anterior mitral valve leaflet and retention of the peripheral margin of coaptation including primary and secondary chordae. The body of the anterior mitral valve leaflet was reconstructed using fresh autologous pericardium, a technique not previously reported in an infant of this size. Three and a half years later, the child is well and has required no further intervention.

Topics: Bioprosthesis; Birth Weight; Captopril; Combined Modality Therapy; Diseases in Twins; Diuretics; Endocarditis, Bacterial; Female; Gentamicins; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Methicillin Resistance; Mitral Valve; Mitral Valve Insufficiency; Pericardium; Rifampin; Staphylococcal Infections; Transplantation, Autologous; Twins, Monozygotic; Vancomycin

A preterm infant had persistent Staphylococcus capitis septicemia with 11 consecutive positive blood cultures over a period of 33 days. The clinical evidence suggested that the source of infection probably originated from the gastrointestinal tract. The combination of rifampin and linezolid treatment, together with prolonged stoppage of enteral feeding, successfully terminated the infection. Rifampin and linezolid should be considered as alternative antimicrobial agents when glycopeptides fail to eradicate Gram-positive pathogens from the host.

Topics: Acetamides; Anti-Infective Agents; Gastrointestinal Tract; Humans; Infant, Newborn; Linezolid; Male; Oxazolidinones; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus

The number of Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia cases is increasing in many European countries. In this observational study in one medical and three surgical ICUs multiple interventions for the treatment and eradication of nosocomial MRSA-pneumonia were used.. Twenty-one critically ill patients (age: 59 +/- 14 years, 15 males/6 females, 18 ventilator-associated, 3 nosocomial, clinical pulmonary infection score > 6 in all patients, APACHE II 18 +/- 5) were enrolled. The patients were treated with a 7-day course of iv linezolid (600 mg bid) plus rifampicin (600 mg bid), endotracheal vancomycin 100 mg qid, thrice daily mouth and throat washing with chlorhexidine 1% fluid and nasal mupirocin ointment, twice daily skin and hair washings with chlorhexidine gluconate 4% and tracheostomy (n = 8) wound care with povidone-iodine spray. Control samples (endotracheal secretions, nose, wound, and pharyngeal swabs) were taken 2, 3, 4, 7 days and 2 months thereafter. Multilobular pneumonia was seen in 16, pleural effusion in 12, and MRSA bacteremia in 4 patients.. One patient died during the follow-up period due to cerebral bleeding. In the remaining 20 patients, pneumonia was clinically cured in all patients and all patients were free of MRSA after eradication. Six patients died due to myocardial infarction (n = 3), gram-negative septic shock (n = 2), herpes encephalitis (n = 1) > 7 days after eradication. No MRSA reinfection occurred during the control period.. We conclude that in patients with MRSA pneumonia an approach using a 7-day course of intravenous linezolid plus rifampicin, intratracheal vancomycin, nasal mupirocin, cutaneous and oropharyngeal chlorhexidin plus povidone-iodine cures pneumonia and is effective for MRSA eradication.

Topics: Acetamides; Aged; Anti-Bacterial Agents; Critical Illness; Cross Infection; Drug Utilization; Female; Humans; Infection Control; Intensive Care Units; Linezolid; Male; Methicillin Resistance; Middle Aged; Oxazolidinones; Pneumonia, Staphylococcal; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Topics: Anti-Bacterial Agents; Aortic Valve; Brain Abscess; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Floxacillin; Gentamicins; Heart Valve Diseases; Humans; Middle Aged; Mitral Valve; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Treatment Outcome

Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of experimental foreign-body infection by Staphylococcus aureus. The antimicrobial efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves) for logarithmic- and stationary-phase bacteria was compared with the in vivo efficacy. In vitro bactericidal activity at clinically relevant concentrations was reached by all drugs except rifampin and linezolid in the log-phase studies but only by levofloxacin in the stationary-phase studies. The bacterial count decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100 mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls, respectively, were: -1.24, -2.26, -2.1, -1.56, -1.47, -1.15, and 0.33 (all groups versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03 versus linezolid). Overall, in vivo efficacy was better predicted by stationary-phase studies, in which it reached a high correlation coefficient even if the rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial efficacy in experimental infection, provide good evidence to support the use of levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for treating patients with orthopedic prosthesis infections.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cloxacillin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Foreign-Body Reaction; Humans; Levofloxacin; Linezolid; Male; Methicillin; Microbial Sensitivity Tests; Ofloxacin; Oxazolidinones; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

We report on a case of arthroscopic treatment of septic arthritis of the elbow joint in a 65-year-old man with an elbow endoprosthesis. Two months after arthroplasty of the elbow joint, the patient developed acute septic arthritis of the right elbow. Methicillin-sensitive Staphylococcus aureus was identified as the causative organism. Six days after the onset of symptoms, the patient was treated with a single arthroscopic procedure of the infected periprosthetic joint, including irrigation with 5 L of Ringer's lactate solution, debridement, and partial synovectomy with a 4.5-mm curved shaver. Intravenous antibiotic therapy was also used for 3 months including rifampicine and fucidic acid according to the intraoperative cultures. The acutely infected total elbow arthroplasty could be cured without removal of the endoprosthesis of the elbow. Ten months postoperatively, the patient remains free of symptoms and his blood rates are within normal limits.

Topics: Aged; Arthritis, Infectious; Arthroplasty, Replacement; Arthroscopy; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Elbow Joint; Fusidic Acid; Humans; Isotonic Solutions; Joint Prosthesis; Male; Methicillin; Ossification, Heterotopic; Osteoarthritis; Prosthesis-Related Infections; Rifampin; Ringer's Lactate; Staphylococcal Infections; Staphylococcus aureus; Therapeutic Irrigation

We report the outcome of debridement and prosthesis retention plus long-term levofloxacin/rifampicin treatment of prosthetic joint infections.. Staphylococcal prosthesis joint infections were defined by positive culture of joint aspirate, intraoperative debridement specimens, or sinus tract discharge in the presence of clinical criteria. Patients received long-term oral levofloxacin 500 mg and rifampicin 600 mg once per day. Sixty patients (age 74.6+/-8.4 years) were included.. Coagulase-negative staphylococci were significantly more frequently isolated in the knee (78.6%; P=.00001). Of the Staphylococcus aureus isolates, 33.3% were methicillin-resistant. Time from arthroplasty to symptoms onset was higher (P=.03) in coagulase-negative staphylococci infections. Global failure was 35% (higher for the knee) and ranged from 16.6% to 69.2% (P=.0045) in patients with symptoms duration of less than 1 month to more than 6 months. A shorter duration of symptoms (P=.001) and time to diagnosis (P=.01) were found in cured patients versus patients showing failure. Among those with S. aureus infections, a higher failure rate was found with methicillin-resistance.. Efficacy was higher in patients with shorter duration of symptoms, earlier diagnosis, hip infections, and methicillin susceptibility.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chi-Square Distribution; Debridement; Drug Administration Schedule; Female; Hip Prosthesis; Humans; Joint Prosthesis; Knee Prosthesis; Levofloxacin; Male; Methicillin Resistance; Ofloxacin; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Treatment Failure; Treatment Outcome

The objective of this paper was to investigate the in vitro effects of linezolid combined with five antistaphylococcal antibiotics--doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin--upon methicillin-susceptible Staphylococcus aureus (MSSA). Five MSSA isolates from clinical specimens of human infections--hf008, hf095, hf295, hf602 and hf946--were used in this study. The checkerboard method was used to assess synergism between linezolid and the five antibiotics, and time-kill curves were carried out with the most active combinations. Indifference was the most common result achieved by the checkerboard method when linezolid was combined with rifampicin, vancomycin or doxycycline. The combination with levofloxacin yielded antagonism for two of the five isolates. However, four isolates showed synergy for the combination of linezolid plus fosfomycin with a fractional inhibitory concentration index (FICI) > or = 0.5. Neither linezolid nor fosfomycin alone inhibited growth at 1/4x minimum inhibitory concentration (MIC); but the combination of both drugs at 1/4 the respective MIC showed a synergistic bacteriostatic effect, a 2-3 log(10) decrease with respect to the most active antibiotic alone. In summary, the combination of subinhibitory.

Topics: Acetamides; Anti-Bacterial Agents; Anti-Infective Agents; Doxycycline; Drug Therapy, Combination; Enzyme Inhibitors; Fosfomycin; Humans; In Vitro Techniques; Levofloxacin; Linezolid; Microbial Sensitivity Tests; Ofloxacin; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

A 21 year old man, previously healthy, presented with subcutaneous nodes consistent with gummas. Ultrasonography disclosed multiple subcutaneous abscesses and images suitable with piomiositis, pleural and pericardium effusion. A puncture-aspirate with fine-needle was performed and produced purulent material, with isolate of Staphylococcus aureus. Antimicrobial susceptibility testing by disk diffusion showed resistant to cefalotin, erythromycin and clindamycin, and susceptibility to trimethoprim-sulfamethoxazole, ciprofloxacin and rifampicin. Methicilin-resistance was confirmed by Staphyslide agglutination testing (Biomérieux). The patient was treated with ciprofloxacin and rifampicin during four weeks, with a good clinical response. The frequency of CA-MRSA infections is increasing, and these are reported in patients without identified predisposing risks leading to failure on empiric therapy for community infections presumed to be due to staphylococcal agents.

Topics: Abscess; Adult; Anti-Infective Agents; Ciprofloxacin; Community-Acquired Infections; Humans; Male; Methicillin Resistance; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcal Skin Infections; Staphylococcus aureus

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Catheters, Indwelling; Diabetes Complications; Discitis; Endocarditis, Bacterial; Fever; Heart Valve Prosthesis; Humans; Hyperparathyroidism, Secondary; Incidence; Kidney Failure, Chronic; Lumbar Vertebrae; Methicillin Resistance; Prognosis; Renal Dialysis; Rifampin; Spain; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Humans; Liability, Legal; Linezolid; Methicillin Resistance; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; United States; Vancomycin

Twenty-three rifampicin-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolated in three wards at a university hospital in Turkey between June, 2000, and February, 2001, were studied for their genetic relatedness using a combination of antibiogram, coagulase serotyping, coagulase gene polymorphism (coa-RFLP), and pulsed-field gel electrophoresis (PFGE). They all expressed high-level rifampicin resistance (MIC, >256 mg/L) and were resistant to gentamicin, kanamycin, amikacin, ciprofloxacin, tetracycline, and cadmium acetate and were susceptible to fusidic acid, vancomycin, trimethoprim, and mupirocin. They belonged to the same coagulase serotype (serotype IV) and had identical coa-RFLP patterns. In contrast, PFGE generated nine banding patterns designated type A, types A1-A5, B, C, and D. The most common PFGE pattern (type A) and its subtypes (types A1-A5) were seen in 20 (87%) of the 23 isolates in the three wards. The results demonstrated the acquisition of rifampicin resistance by different MRSA clones and the spread of one clone among patients in the three wards.

Topics: Coagulase; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Serotyping; Staphylococcal Infections; Staphylococcus aureus; Turkey; Urease

Citalopram, a selective serotonin reuptake inhibitor, is used in the management of anxiety disorders. A 55-year-old man receiving citalopram for panic disorder reported a decrease in the agent's therapeutic efficacy when rifampin was started for osteomyelitis. His condition improved when the rifampin was stopped. Rifampin is known to induce the metabolism of cytochrome P450 3A4 substrates and thus plays a role in several drug-drug interactions. We suspect that the efficacy of citalopram was blunted with the concurrent use of rifampin. To our knowledge, only one other case of an interaction of rifampin with a selective serotonin reuptake inhibitor is described in the literature. Clinicians should monitor all drugs and dietary supplements that patients with psychiatric conditions take, regardless of the indication, intended purpose, or prescriber. This is especially important, however, for a drug that is pivotal to a patient's well-being; its therapeutic effect should be carefully monitored when any new drug is added or a change in the dosage of a concurrent drug is made.

Topics: Anti-Bacterial Agents; Citalopram; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Antagonism; Enzyme Induction; Humans; Male; Middle Aged; Panic Disorder; Rifampin; Selective Serotonin Reuptake Inhibitors; Staphylococcal Infections

Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis.. A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed.. Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones.. Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Therapy, Combination; Methicillin Resistance; Minocycline; Osteomyelitis; Rabbits; Radiography; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Vancomycin

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been reported in patients with recognized predisposing risk factors in several cities in the United States and across the world. Reviewing risk factors in adult patients with CA-MRSA in Kentucky has not been reported.. To determine the risk factors of 15 patients with CA-MRSA in Louisville KY, to compare the sensitivities of each pathogen and to recommend management.. An infectious diseases private practice in Louisville, KY.. This is a case series of patients with CA-MRSA. The disease course for each patient was reviewed for risk factors, such as participation in physical contact sports and prison exposure. The antimicrobial sensitivities of each pathogen were also reviewed. Recommendations were produced from the information obtained.. A total of 15 patients were reviewed. Five patients had a family member or significant-other with a current CA-MRSA infection. Three had traditional risk factors (healthcare workers). All of the isolates were susceptible to vancomycin and resistant to oxacillin. All of the isolates tested for trimethoprim/sulfamethoxazole (TMP/SMX), tetracycline, and rifampin were sensitive. A majority (83%) of those tested for clindamycin and only 50% of those tested for levofloxacin were sensitive. All isolates tested for cefazolin were resistant.. An emerging risk factor for acquiring an MRSA skin and soft tissue infection is having a significant-other with a current diagnosis of CA-MRSA. After incision and drainage, a review of the antimicrobial sensitivities indicates that oral treatment may be adequate for a selection of cases.

Topics: Adult; Anti-Bacterial Agents; Cefazolin; Clindamycin; Community-Acquired Infections; Erythromycin; Female; Humans; Kentucky; Levofloxacin; Male; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Ofloxacin; Oxacillin; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Tetracycline; Trimethoprim; Vancomycin

Methicillin-resistant Staphylocosis aureus (MRSA) is an emerging infection in patients with cystic fibrosis (CF). MRSA may be a management dilemma for healthcare workers (HCWs) with CF. Eradication of MRSA with long-term rifampicin and fusidic acid can be achieved in patients with CF. We describe a case of recurrent MRSA infection in a HCW with CF. Molecular typing of the MRSA isolates supported re-infection rather than re-emergence of an earlier MRSA infection. Infection control advice for HCWs with CF who acquire MRSA remains controversial.

Topics: Adult; Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Female; Follow-Up Studies; Fusidic Acid; Health Personnel; Humans; Methicillin Resistance; Rifampin; Sputum; Staphylococcal Infections; Staphylococcus aureus

Topics: Adult; Anti-Bacterial Agents; Humans; Knee Injuries; Male; Methicillin Resistance; Plasmapheresis; Purpura, Thrombotic Thrombocytopenic; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

A 60-year-old man presented with ureteric obstruction secondary to a mycotic right common iliac artery aneurysm complicating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The diagnosis of MRSA was not known at the time of surgery, and in situ replacement of the aneurysm using a rifampicin-bonded prosthesis was performed. The patient made a full recovery, and to date there is no evidence of residual or recurrent infection. To our knowledge, this is the first reported case of mycotic iliac aneurysm infected with MRSA in the literature. We discuss the consequences and the considerable diagnostic and therapeutic problems that arise.

Topics: Aneurysm, Infected; Antibiotics, Antitubercular; Bacteremia; Humans; Iliac Aneurysm; Male; Methicillin Resistance; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Ureteral Obstruction

Infection can be a devastating complication after implantation of a cortical bone allograft. The allograft could act as a vehicle for local antibiotic prophylaxis.. We studied the release of antibiotics in vitro from cortical bone allografts impregnated with antibiotics for different periods of time. We also studied whether cortical allografts impregnated with antibiotics could eradicate Staphylococcus aureus from an experimentally infected graft in vivo. In the in vitro study, pieces of cortical bone were impregnated with netilmicin, vancomycin, ciprofloxacin and rifampicin for 1 h, 10 h and 100 h. The antibiotics were eluted into phosphate-buffered saline (PBS) for 7 days, with daily transfer of the bone into fresh PBS. In the in vivo study, cortical allografts impregnated with antibiotics were placed in rats intramuscularly. 10 microL of an S. aureus suspension (0.6 x 10(5) CFU) was placed in the intramedullary cavity. After 15 days, the allografts were removed and examined for bacterial growth.. The amount of antibiotics released in vitro was influenced by the time used for antibiotic impregnation of the bone. Allografts impregnated with netilmicin, vancomycin and rifampicin effectively eradicated perioperative contamination with S. aureus in vivo.. This study shows that a cortical bone allograft would be an effective vehicle for local antibiotic delivery.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bone Transplantation; Femur; Netilmicin; Postoperative Complications; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Transplantation, Homologous; Vancomycin

Acquired antimicrobial resistance is commonly attributed to regimens that expose bacteria to subinhibitory concentrations; consequently, eradication of susceptible cells is advocated. The mutant selection window hypothesis predicts that resistance can be acquired even when inhibitory concentrations are exceeded and susceptible bacteria are eradicated. The objective was to test that prediction clinically.. Tuberculosis patients (n = 372) were sampled for nasal colonization by Staphylococcus aureus at the beginning of anti-tuberculosis therapy with rifampicin-containing regimens and again after 2 and 4 weeks. Rifampicin susceptibility of S. aureus was determined, and S. aureus isolates from patients developing acquired resistance were examined by molecular strain typing. Diabetes patients (n = 200) served as untreated controls.. Nasal colonization was 17% and 20% for the tuberculosis and diabetes patients, respectively. Four patients were initially colonized with rifampicin-resistant S. aureus and were excluded from further sampling. Initiation of anti-tuberculosis therapy eradicated S. aureus nasal colonization in 53/58 tuberculosis patients while allowing acquisition of rifampicin resistance in 5/58. Pulsed-field gel electrophoresis (PFGE) band patterns and protein A repeat sequence determination differed in S. aureus isolated from different patients but was identical in isolates obtained from the same patient before and after acquisition of resistance. No resistance was acquired in untreated control patients, which differed statistically from treated patients (P = 0.025).. Acquired resistance and eradication of susceptible bacteria can occur concurrently; restricting acquired resistance may require direct suppression of mutant growth and viability in addition to elimination of susceptible bacteria.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carrier State; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Male; Middle Aged; Nasal Cavity; Polymorphism, Restriction Fragment Length; Rifampin; Selection, Genetic; Staphylococcal Infections; Staphylococcal Protein A; Staphylococcus aureus; Tuberculosis

Topics: Acetamides; Aged; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Linezolid; Male; Methicillin Resistance; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Treatment Outcome; Tricuspid Valve

To investigate the prophylactic efficacy of systemic, topical, or combined antibiotic usage in the prevention of late prosthetic vascular graft infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and the differential adherence of S. epidermidis to Dacron and ePTFE grafts in a rat model.. Graft infections were established in the back subcutaneous tissue of 120 adult male Wistar rats by implantation of 1-cm(2) Dacron/ePTFE prosthesis followed by topical inoculation with 2 x 10(7) CFU of clinical isolate of MRSE. Each of the series included one group with no graft contamination and no antibiotic prophylaxis (uncontaminated control), one contaminated group that did not receive any antibiotic prophylaxis (untreated control), one contaminated group in which perioperative intraperitoneal prophylaxis with vancomycin (10 mg/kg) was administered, two contaminated groups that received rifampicin-soaked (5 mg/1 ml) or vancomycin-soaked (1 mg/1 ml) grafts, and one contaminated group that received a combination of rifampicin-soaked (5 mg/1 ml) graft with perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were removed sterilely 7 days after implantation and evaluated by using sonication and quantitative blood agar culture.. MRSE had significantly greater adherence to Dacron than ePTFE grafts in the untreated contaminated groups (P < 0.001). Rifampicin had better efficacy than vancomycin in topical application, but the difference was not statistically significant (P > 0.05). Intraperitoneal vancomycin showed a significantly higher efficacy than topical vancomycin or rifampicin (P < 0.001). The best results were provided by a combination of intraperitoneal vancomycin in rifampicin-soaked graft groups (P < 0.001).. The combination of rifampicin and intraperitoneal vancomycin seems to be the best choice for the prophylaxis of late prosthetic vascular graft infections caused by MRSE.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Disease Models, Animal; Drug Therapy, Combination; Male; Methicillin Resistance; Polyethylene Terephthalates; Polytetrafluoroethylene; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

A vancomycin-resistant Staphylococcus aureus (VRSA) isolate was obtained from a patient in Pennsylvania in September 2002. Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification. The MICs of a variety of antimicrobial agents were determined by broth microdilution and macrodilution methods following National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The isolate was resistant to vancomycin (MIC = 32 micro g/ml), aminoglycosides, beta-lactams, fluoroquinolones, macrolides, and tetracycline, but it was susceptible to linezolid, minocycline, quinupristin-dalfopristin, rifampin, teicoplanin, and trimethoprim-sulfamethoxazole. The isolate, which was originally detected by using disk diffusion and a vancomycin agar screen plate, was vancomycin susceptible by automated susceptibility testing methods. Pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA indicated that the isolate belonged to the USA100 lineage (also known as the New York/Japan clone), the most common staphylococcal PFGE type found in hospitals in the United States. The VRSA isolate contained two plasmids of 120 and 4 kb and was positive for mecA and vanA by PCR amplification. The vanA sequence was identical to the vanA sequence present in Tn1546. A DNA probe for vanA hybridized to the 120-kb plasmid. This is the second VRSA isolate reported in the United States.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Proteins; Blotting, Southern; Carbon-Oxygen Ligases; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Ofloxacin; Oxacillin; Penicillins; Pennsylvania; Plasmids; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Staphylococcal Infections; Vancomycin; Vancomycin Resistance

After infection of non-phagocytic cells, some Staphylococcus aureus strains are able to survive and kill their host cells. The purpose of this study was to determine the action of various antibiotics on the survival of host cells and/or intracellular S. aureus.. Murine keratinocyte (PAM212) and fibroblast (mKSA) cell lines were infected with cytotoxic S. aureus and cultured in the presence of various antibiotics at graded concentrations. The viability of host cells was measured 24 h after infection. To determine the bacterial viability within host cells, cellular lysates were prepared and colony forming units were quantified using a spiral plater. Host cells infected with fluorescein isothiocyanate (FITC)-labelled S. aureus were analysed by flow cytometry and microscopy to determine the subcellular localization S. aureus.. Oxacillin, vancomycin, gentamicin, ciprofloxacin and trimethoprim/sulfamethoxazole did not rescue host cells from cell death induced by intracellular S. aureus. In contrast, linezolid, rifampicin, azithromycin, clindamycin, erythromycin and quinupristin/dalfopristin suppressed the cytotoxic action of S. aureus. After withdrawal of antibiotics, intracellular S. aureus regained cytotoxic activity and killed their host cells. Only rifampicin was able to eliminate intracellular S. aureus completely within 72 h. In contrast, clindamycin, azithromycin and linezolid induced a state of intracellular persistence of viable S. aureus.. Antibiotics commonly used for the management of S. aureus infections appear to create a niche for invasive intracellular S. aureus, which may play an important role for persistence and recurrence of infection. Because of its unique ability to eliminate intracellular S. aureus, rifampicin appears to be valuable for the treatment of invasive S. aureus infections.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antibodies, Bacterial; Cell Survival; Cells, Cultured; Colony Count, Microbial; Dose-Response Relationship, Drug; Flow Cytometry; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Mice; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Subcellular Fractions

Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

Topics: Acetamides; Aged; Aged, 80 and over; Anti-Infective Agents; Female; Humans; Linezolid; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin; Vancomycin Resistance

Qualitative broth culture and quantitative culture on agar were compared with quantitative polymerase chain reaction (PCR) for the diagnosis of foreign body infections (FBI) in a rat model with and without exposure to systemic antibiotics (teicoplanin and rifampin). The 3 methods had a similar and high yield without antibiotics. Antibiotics decreased the number of CFU/foreign body and increased the number of culture-negative foreign bodies and the variability of the results in quantitative culture. The yield of broth culture remained high under antibiotics although prolonged incubation (2-5 days) was required. The yield of the PCR was equivalent or even superior (for teicoplanin) to the yield of broth culture. Quantitative PCR had a higher yield and lower variability than quantitative culture and was not affected by antibiotics. The simultaneous isolation of RNA from all samples indicated viability of the bacteria. Quantitative PCR seems a promising method for the diagnosis of FBI.

Topics: Animals; Anti-Infective Agents; Colony Count, Microbial; DNA, Bacterial; Polymerase Chain Reaction; Prosthesis-Related Infections; Rats; Rats, Inbred F344; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six male, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation=6.3) years and FEV(1) of 36.1% (standard deviation=12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field gel electrophoresis. Five of the seven had no evidence of MRSA during and for at least six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P<0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3+/-17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P=0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Carrier State; Chronic Disease; Cross Infection; Cystic Fibrosis; Female; Fusidic Acid; Humans; Male; Methicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

A 68-year old man with fever chills and a diastolic murmur was diagnosed with aortic-valve endocarditis caused by coagulase-negative Staphylococcus lugdunensis. The clinical condition initially improved with antibiotic therapy. On day seven, transoesophageal echocardiography revealed large abscesses extending from the aortic root to the left ventricular wall. Emergency cardiac surgery was performed successfully and a stentless bioprosthetic valve was inserted. S. lugdunensis endocarditis is known for its aggressive clinical course with valve destruction, abscess formation and embolic complications despite appropriate antibiotics. Antibiotic treatment alone is associated with a high mortality rate which can be reduced by early valve replacement.

Topics: Abscess; Aged; Aorta, Thoracic; Aortic Valve; Cefuroxime; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography; Echocardiography, Transesophageal; Endocarditis, Bacterial; Humans; Male; Microbial Sensitivity Tests; Pericardial Effusion; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

Eradication of Staphylococcus aureus biofilms after rifampin treatment was tested in a mouse model of device-related infection by using biophotonic imaging. Following treatment, the bioluminescent signals decreased to undetectable levels, irrespective of the age of the biofilm. After the final treatment, the signals rebounded in a time-dependent manner and reached those for the untreated mice. Readministration of rifampin was unsuccessful in eradicating reestablished infections, with the rifampin MICs for such bacteria being increased and with the bacteria having point mutations in the rpoB gene.

Topics: Animals; Antibiotics, Antitubercular; Biofilms; Colony Count, Microbial; Diagnostic Imaging; DNA-Directed RNA Polymerases; Luminescent Measurements; Mice; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.

Topics: Anti-Bacterial Agents; Cerebrospinal Fluid; Fusidic Acid; Humans; Inflammation; Male; Meningitis, Bacterial; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

In situ replacement of infected vascular grafts is an accepted alternative to total graft excision and extraanatomic replacement. Its success relies upon the ability of the newly inserted graft to resist recurrent infection. This study compares the efficacy of two methods used to reduce the risk of graft reinfection: rifampicin soaking versus silver bonding of grafts. The grafts' resistance to infection was tested in vitro in two protocols, each using a panel of seven common bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The length of time the grafts remained free of organisms was compared between the groups. Both the silver graft and the rifampicin-soaked graft were significantly better than control graft at preventing bacterial growth on the graft surface. The rifampicin inhibited the growth of the gram-positive organisms, including MRSA, significantly better than the silver graft on days 2 and 3 (p < 0.001). Conversely, the silver graft was significantly more effective against the gram-negative organisms until day 4 (p < 0.0001). Both types of graft inhibit the in vitro growth of bacteria more effectively than controls, with rifampicin being most effective against gram-positive organisms and silver being best against the gram-negative organisms.

Topics: Acetates; Animals; Antibiotics, Antitubercular; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Disease Models, Animal; Escherichia coli Infections; Horses; Methicillin Resistance; Models, Cardiovascular; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Silver Compounds; Staphylococcal Infections; Time Factors

This study employs time-kill techniques to examine the most common drug combinations used in the therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin plus either gentamicin or rifampin. Community-associated MRSA were more likely to be synergistically inhibited by combinations of vancomycin and gentamicin versus vancomycin alone compared to inhibition associated with hospital-acquired strains.

Topics: Community-Acquired Infections; Drug Synergism; Drug Therapy, Combination; Gentamicins; Humans; Kinetics; Methicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

This study compares in vitro antimicrobial resistance development between strains of Staphylococcus aureus including newly described community-acquired methicillin-resistant strains (CA-MRSA). High-level resistance developed in all strains of S. aureus after exposure to rifampicin and gentamicin and in some strains after fusidic acid exposure, independent of methicillin resistance phenotype. Resistance did not develop after exposure to clindamycin, cotrimoxazole, ciprofloxacin, linezolid, or vancomycin. These results have important implications for therapy of CA-MRSA infections.

Topics: Community-Acquired Infections; Drug Resistance, Multiple; Gentamicins; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Prevalence; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Staphylococci are a major cause of infections associated with indwelling medical devices. Biofilm formation on these devices adds to the antibiotic resistance seen among clinical isolates. RNAIII-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal pathogenesis, including biofilm formation, by obstructing quorum sensing mechanisms. Bismuth ethanedithiol (BisEDT) also prevents biofilm formation at subinhibitory concentrations. RIP and BisEDT were combined to prevent infections in a rat graft model, using antibiotic sensitive and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. BisEDT, RIP, or rifampin, or their combinations reduced the graft associated bacterial load over seven days. BisEDT-RIP was the best combination, reducing bacterial load to undetectable levels. BisEDT-RIP may prove useful for coating medical devices to prevent staphylococcal infections.

Topics: Animals; Biofilms; Drug Resistance, Bacterial; Drug Synergism; Implants, Experimental; Male; Mercaptoethanol; Models, Biological; Oligopeptides; Polyethylene Terephthalates; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

Topics: Abscess; Disinfection; Drug Resistance, Multiple; Family Health; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcal Skin Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Concentrations of the calcium-binding proteins of the S100 family, myeloid-related proteins 8 and MRP 14 (MRP8/14), are elevated in chronic infections, yet the role of these proteins is not clearly defined. Using commercial and developed enzyme immunoassays, we assayed for MRP8/14 in sterile-filtered abscess fluid from tissue-cage-implanted rats and rabbits. Staphylococcus aureus abscesses were created 6 weeks after the intraperitoneal implantation of tissue cages. Leukocytes, bacteria, and non-protein-bound calcium and zinc were measured in the infection exudate at day 3 or 5 of infection and after 8 days of treatment with antimicrobials beta-lactams (18 rabbits, 35 rats) and fluoroquinolone-rifampin (6 rabbits). Half of the infected rats were depleted of neutrophils; these rats exhibited significantly lower MRP 8/14 concentrations on all days sampled, regardless of the level of infection. The level of abscess MRP 8/14 is high early in the course of infection but decreases with effective antimicrobial treatment by as much as 100-fold. Thirty-day-old abscesses with log 6 bacterial counts and low neutrophil counts showed low concentrations of MRP 8/14 in these models. In abscess fluid, interleukin-6, as a representative marker of inflammation, correlated with MRP8/14, whereas ionized calcium and zinc did not. Our data suggest that infection and inflammation are not equal stimuli for MRP 8/14. The neutrophil appears to be the main source of MRP8/14 in this model.

Topics: Abscess; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Calcium; Calgranulin A; Calgranulin B; Cations, Divalent; Chlorides; Disease Models, Animal; Exudates and Transudates; Fluoroquinolones; Immunoenzyme Techniques; Inflammation; Interleukin-6; Lactams; Leukocyte Count; Neutrophils; Rabbits; Rats; Rifampin; Staphylococcal Infections; Zinc

Tuberculous otitis media (TOM) is a rare cause of chronic suppurative infection of the middle ear. Due to that the symptoms and signs are often indistinguishable from those of nontuberculosis chronic otitis media and the fact that the index of suspicion is low, there is frequently a considerable delay prior to diagnosis. This can lead to irreversible complications such as facial nerve paralysis and labyrinthitis. Medical therapy with antituberculous drugs is usually effective. We report three cases with TOM diagnosticated and followed up in our Service from january 1993 to july 2001. Their charts were retrospectively reviewed for relevant historical data, physical findings, complementary studies, treatment and clinical response. We performed a review of the literature, emphasizing that TOM should be considered in the differential diagnosis of chronic otitis media.

Topics: Adult; Aged; Amoxicillin; Antitubercular Agents; Cerebrospinal Fluid Otorrhea; Drug Combinations; Ear Diseases; Female; Humans; Isoniazid; Male; Mycobacterium Infections; Mycobacterium tuberculosis; Otitis Media; Penicillins; Proteus Infections; Proteus mirabilis; Pyrazinamide; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Topics: Aged; Arthritis, Infectious; Arthritis, Rheumatoid; Arthroplasty, Replacement, Knee; Autoimmune Diseases; Ciprofloxacin; Cloxacillin; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Knee Prosthesis; Male; Phlebitis; Postoperative Complications; Prosthesis-Related Infections; Pulmonary Embolism; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus; Virulence

Infection continues to be one of the major complications of cerebro-spinal fluid shunting procedures. Recent insights in the pathophysiological mechanism of these foreign body infections have elucidated the difficulty of achieving successful treatment without device removal. The development of a rifampin-impregnated silicone catheter yielded excellent results in infection prevention and treatment in vitro as well as in an animal model.. Here, we describe the application of this device in two patients with a complicated course of shunt infection.. In one patient the rifampin-impregnated shunt system was implanted after external drainage to prevent further infection. The shunt infection of the second patient was treated by replacement of the infected shunt system with a rifampin-impregnated device. Both patients recovered immediately without any signs of adverse effects and the two shunt systems have now been working properly for more than 36 and 21 months, respectively.. These results suggest that rifampin-impregnated silicone catheters could become a valuable tool in the treatment and prevention of shunt infections.

Topics: Anti-Bacterial Agents; Catheterization; Cerebrospinal Fluid Shunts; Female; Humans; Rifampin; Silicones; Staphylococcal Infections; Staphylococcus epidermidis

Methicillin-resistant Staphylococcus aureus is becoming increasingly prevalent as both a nosocomial and a community-acquired pathogen. Daptomycin, a lipopeptide antibiotic now in phase III clinical trials, is rapidly bactericidal in vitro against a range of gram-positive organisms, including methicillin-resistant S. aureus (MRSA). In this study, we compared the efficacy of daptomycin with that of vancomycin, each with or without rifampin, in a model of experimental aortic valve endocarditis due to MRSA. The infecting strain (MRSA strain 32) was susceptible to daptomycin (MIC = 1 micro g/ml), vancomycin (MIC = 0.5 micro g/ml), and rifampin (MIC = 0.5 micro g/ml). Daptomycin was administered at 25 or 40 mg/kg q24h (q24h) by subcutaneous injection in an attempt to simulate human doses of 4 and 6 mg/kg q24h, respectively. Vancomycin was given at 150 mg/kg q24h by continuous intravenous infusion. Rifampin was given at 25 mg/kg by intramuscular injection q24h. Treatment was started 6 h postinoculation and continued for 4.5 days. Outcome was assessed by counting the residual viable bacteria in vegetations. The mean peak daptomycin levels in serum at 2 h after subcutaneous administration of 25 and 40 mg/kg were 64 and 91 micro g/ml, respectively. Daptomycin was undetectable in serum at 24 h. The total exposure was comparable to that achieved clinically in humans receiving the drug. Bacterial counts (mean log(10) number of CFU per gram +/- the standard deviation) in untreated controls reached 10.6 +/- 0.8. In treated rats, bacterial counts were as follows: vancomycin, 7.1 +/- 2.5; daptomycin at 25 mg/kg, 5.5 +/- 1.7; daptomycin at 40 mg/kg, 4.2 +/- 1.5. The difference between daptomycin at 40 mg/kg and vancomycin at 150 mg/kg was statistically significant (P = 0.004). In the study of combination therapy, vegetation bacterial counts were as follows: daptomycin at 40 mg/kg, 4.6 +/- 1.6; rifampin, 3.6 +/- 1.3; vancomycin plus rifampin, 3.3 +/- 1.1; daptomycin plus rifampin, 2.9 +/- 0.8. The difference between daptomycin and daptomycin plus rifampin was statistically significant (P = 0.006). These results support the continued evaluation of daptomycin for serious MRSA infections, including infective endocarditis.

Topics: Animals; Anti-Bacterial Agents; Daptomycin; Drug Therapy, Combination; Endocarditis, Bacterial; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Sprague-Dawley; Rifampin; Staphylococcal Infections; Staphylococcus aureus

It was the aim of the study to examine the efficacy of silver coated prostheses in comparison to Rifampin in impregnated prostheses in the prevention of vascular graft infections.. 24 C3H/HcN mice with a bodyweight between 24 and 27 grams were assigned to four different groups. GROUP I: control gel-sealed Dacron graft (Uni-Graft DV) (6), GROUP II: gel-sealed Dacron graft (Uni-Graft DV) contaminated locally with 2 x 10(7) CFU/1.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP III: silver prosthesis (Intergard Silver) contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP IV: Rifampin impregnated prosthesis contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6). 14 days after primary operation all animals were euthanized and the grafts harvested. Specimens were examined for signs of infections by histology and microbiology.. At termination of the trial on day 14 none of the grafts of group I were contaminated. 6 out of 6 grafts in group II, 6 out of 6 grafts in group III and 1 out of 6 grafts in group IV presented with infected grafts. The use of antimicrobial Rifampin could significantly prevent infection after bacterial challenge in group IV.. The silver protected prosthesis (Intergard Silver) seems to be not effective in protecting vascular infection in vivo. However, the Rifampin group showed excellent results. In conclusion Rifampin bonded gelatin-sealed Dacron grafts are significantly more resistant to bacteremic infection than are silver/collagen-coated Dacron grafts.

Topics: Animals; Blood Vessel Prosthesis; Coated Materials, Biocompatible; Colony Count, Microbial; Male; Mice; Mice, Inbred C3H; Polyethylene Terephthalates; Prosthesis Design; Prosthesis Failure; Prosthesis-Related Infections; Rifampin; Silver; Staphylococcal Infections; Subcutaneous Tissue; Surgical Wound Infection

Association of rifampicin with polybutylcyanoacrylate nanoparticles provided considerable enhancement of drug antibacterial activity. In vitro nanoparticle-loaded rifampicin was more active against Staphylococcus aureus and Mycobacterium avium, localized in isolated alveolar macrophages. Level of rifampicin in macrophages increased 2-3-fold after incubation with rifampicinloaded nanoparticles comparing to the free drug. High therapeutic efficacy of colloidal rifampicin was demonstrated in vivo. Use of nanoparticles provided 2-fold increase in rifampicin efficacy, comparing with the free drug at treatment of staphylococcus sepsis in mice. Single administration of nanoparticulate rifampicin in the dose 25 mg/kg resulted in 80% survival of mice with salmonellosis, while 50 mg/kg of free rifampicin could provide only 10% survival. It may be considered that high antibacterial efficacy of rifampicin bound to nanoparticles is due to its effective delivery to macrophages.

Topics: Animals; Anti-Bacterial Agents; Colloids; Drug Carriers; Enbucrilate; Humans; Injections, Intravenous; Macrophages, Alveolar; Mice; Mycobacterium avium; Rabbits; Rifampin; Salmonella Infections; Salmonella typhimurium; Sepsis; Staphylococcal Infections; Staphylococcus aureus

The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combination were similar to those in the respective linezolid-only treatment groups. At therapeutic levels of linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the linezolid dosing, it did not antagonize the efficacy of linezolid.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colony Count, Microbial; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valves; Kidney; Linezolid; Male; Methicillin; Microbial Sensitivity Tests; Oxazolidinones; Penicillins; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Adult; Aortic Valve; Diagnosis, Differential; Drug Therapy, Combination; Dysarthria; Endocarditis, Bacterial; Facial Paralysis; Gentamicins; Heart Valve Prosthesis Implantation; Humans; Male; Oxacillin; Penicillins; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Time Factors

This study was performed to evaluate the interaction of erythromycin or rifampin with vancomycin against Staphylococcus epidermidis biofilms.. Biofilm-forming S. epidermidis strains (ATCC 35983, 35984) and polyurethane (PU) sheets were incubated for the formation of bacterial biofilms. Biofilms on PU sheets were treated with various antibiotic regimens. The number of viable bacteria on the sheets was counted.. While erythromycin or vancomycin alone did not significantly reduce the biofilm bacterial concentration, the combination of vancomycin and erythromycin resulted in a clear reduction in bacterial concentration compared with the single agents. Rifampin was the most active single agent against biofilm-forming S. epidermidis, while the combination of rifampin and vancomycin showed further reduction in bacterial concentration.. These data suggest that the combination of erythromycin or rifampin and vancomycin is more effective than vancomycin alone in the treatment of biofilm infections caused by biofilm-forming S. epidermidis.

Topics: Biofilms; Colony Count, Microbial; Drug Therapy, Combination; Erythromycin; Humans; Polyurethanes; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

To evaluate the efficacy of silver- or Triclosan-coated prosthetic material compared to Rifampin bonded Dacron concerning their resistance to infection following subcutaneous implantation and contamination with Staphylococcus aureus.. Animal experimental study in mice.. Thirty-six C3H/HcN mice (Charles River Lab., Sulzfeld, Germany) with a weight between 24 and 27 g were randomised into six groups counting six animals each. Group I: control, gel-sealed dacron graft, group II: gel-sealed dacron graft and local contamination, group III: Intergard-Silver-prosthesis and contamination, group IV: silver/gel-sealed dacron prosthesis (test graft) and contamination, group V: Rifampin-bonded gel-sealed graft and contamination, group VI: Triclosan/collagen-coated dacron graft and contamination. Dacron graft material 0.8x1 cm was subcutaneously implanted in mice. Local contamination with 2x10(7)/0.2 ml S. aureus ATCC 25923 was carried out in groups II to VI. On day 14 the animals were killed and the grafts were explanted. The microscopic, histologic and microbiological evaluation of the graft material and the perigraft tissue was performed.. In control group I no case of infection was detected. In group II, 6 of 6 animals showed infection. In group III (Intergard-Silver) and group IV (silver/gel-test graft) were 6 of 6, in group V (Rifampin) only 1 of 6 grafts and in group VI (Triclosan) 4 of 6 grafts were infected. The difference between the low rate of infection in group V (Rifampin) in comparison to the completely infected groups III and IV (Silver) as well as the control group II was significant. Treatment of grafts with Triclosan could prevent infection only in 1/3 of the cases in group IV.. Silver coating failed to prevent graft infection material. A potential antimicrobial property was evident for Triclosan whereas Rifampin-bonded grafts exhibit a significantly reduced infection rate. Thus, silver-coated vascular grafts cannot ensure protection from vascular graft infection.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Male; Mice; Mice, Inbred C3H; Polyethylene Terephthalates; Prosthesis-Related Infections; Rifampin; Silver; Staphylococcal Infections; Triclosan

The hyper-IgE syndrome is a rare primary immunodeficiency characterized by recurrent staphylococcal infections and high levels of serum IgE.. The case of a 28-year-old man with epidural and paravertebral abscesses and a markedly elevated serum IgE level of 2,609 U/ml is reported. There was no allergic diathesis, nor had the patient a history of other diseases, which might explain the high serum IgE level. In a blood culture, Staphylococcus aureus was detected. Since early childhood, the patient has suffered from recurrent skin infections.. The presented study case discusses the diagnosis of a Job's syndrome in this patient and reviews previously published cases. It also summarizes the current knowledge about pathogenesis and diagnostic criteria of this rare syndrome.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cefazolin; Diagnosis, Differential; Drainage; Follow-Up Studies; Humans; Immunoglobulin E; Job Syndrome; Male; Psoas Abscess; Rifampin; Staphylococcal Infections; Time Factors; Tomography, X-Ray Computed

To isolate bacteria, mycoplasma and chlamydia from the urogenital tract, and to determine their antibiotic susceptibility.. Bacteria, mycoplasma and chlamydia were isolated from the urogenital tract secretion by artifical culture, and their antibiotic susceptibility was detected by disk diffusion.. The common microorganisms were S. epidermidis and corynebacberium, and the minority microorganisms were G- bacteria or E. coli. Bacteria were susceptible to amikacin, cephazolin V, rifampin, gentamycin, and docycyclin.. S. epidermidis and corynebacterium are important pathogens of the urogenital tract infection. Disk susceptibility test can be used to screen the susceptible antibiotic.

Topics: Adult; Amikacin; Cefazolin; Chlamydia; Corynebacterium; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prostatitis; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Urethritis; Uterine Cervicitis

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow Transplantation; Catheterization, Central Venous; Catheters, Indwelling; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance; Female; Humans; Infection Control; Leukemia; Male; Middle Aged; Minocycline; Neutropenia; Rifampin; Staphylococcal Infections; Texas

Linezolid is a synthetic antimicrobial agent which was introduced into clinical therapy in the early 2001. It has an inhibitory effect against most of the Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci. In this study, in-vitro activities of linezolid, teicoplanin, vancomycin, ciprofloxacin, gentamicin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole and rifampicin, were tested against 164 methicillin-resistant Staphylococcus spp. (96 S. aureus and 68 coagulase negative staphylococci) isolated from clinical specimens, by using disk diffusion method. None of the strains were found to be resistant to linezolid, vancomycin and teicoplanin. The resistance rates to other drugs were as follows; 80.5% to ciprofloxacin, 78.0% to gentamicin, 76.8% to erythromycin, 65.5% to clindamycin, 57.3% to trimethoprim/sulfamethoxazole and 41.5% to rifampicin. It was concluded that linezolid can be used as an alternative drug in severe infections caused by methicillin-resistant Staphylococcus spp., especially if the isolate was found to be resistant to teicoplanin or a side effect of vancomycin was observed.

Topics: Acetamides; Anti-Infective Agents; Ciprofloxacin; Clindamycin; Drug Resistance, Bacterial; Erythromycin; Gentamicins; Humans; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Delayed complications associated with sublaminar and interspinous wiring in the pediatric cervical spine are rare. The authors present a case of delayed complication in which a cervical fusion wire migrated into the cerebellum, causing subsequent cerebellar abscess 2 years after posterior cervical arthrodesis. A craniotomy was required to remove the wire and drain the abscess. Despite their history of safety and successful fusion, procedures involving sublaminar and interspinous wiring carry a risk of neurological injury secondary to wire migration. A thorough neuroimaging evaluation is required in patients who have undergone fusion and who have neurological complaints to detect late instrumentation-related sequelae.

Topics: Adolescent; Anti-Bacterial Agents; Bone Wires; Brain Abscess; Cerebellar Diseases; Cervical Vertebrae; Foreign-Body Migration; Humans; Magnetic Resonance Imaging; Male; Nafcillin; Penicillins; Reoperation; Rifampin; Spinal Fusion; Staphylococcal Infections; Tomography, X-Ray Computed

Addition of intravenous rifampin is reported to be useful in prompt clearance of persistent coagulase negative staphylococcal (CONS) bacteraemia in high-risk neonates. Four neonates (mean birthweight 823 g, mean gestation 25 wk) with persistent CONS bacteraemia for > 7-10 d (mean 11) were treated with i.v. rifampicin (10 mg/kg/12 h x 10 d) while continuing vancomycin (15 mg/kg/24 h). Their age at time of infection ranged from 2 to 11 d. The mean (range) vancomycin peak and trough concentrations were 29 (25-35) and 6 (4-10) microg/ml, respectively. The blood isolates were Staphylococcus epidermidis, S. hominis, and S. haemolyticus. Addition of rifampicin was associated with prompt clearance of bacteraemia within 48 h (n = 3) and 5 d (n - 1). Rifampicin-related adverse effects such as abnormal liver function tests and thrombocytopenia did not occur.. Addition of i.v. rifampicin to vancomycin may optimize the outcome of persistent CONS bacteraemia and the risk of bacterial resistance related to prolonged exposure to vancomycin.

Topics: Bacteremia; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Intensive Care Units, Neonatal; Male; Rifampin; Severity of Illness Index; Staphylococcal Infections; Treatment Outcome

Recently, concern has increased regarding the spread of methicillin-resistant Staphylococcus aureus (MRSA) in the community. We studied 812 subjects from central Italy to establish the rates of nasal carriage of S. aureus, and antibiotic susceptibility patterns, in the community. The prevalence of S. aureus nasal carriage was 30.5%. Only one subject, with predisposing risk factors for acquisition, was identified as carrier of MRSA (prevalence of 0.12%). The presence of MRSA in the community of our area still appears to be a rare event. Among methicillin-susceptible S. aureus (MSSA) isolates, a surprisingly high rate (18%) of resistance to rifampin was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Proteins; Carrier Proteins; Community-Acquired Infections; DNA Primers; Drug Resistance, Multiple; Female; Hexosyltransferases; Humans; Infection Control; Italy; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Muramoylpentapeptide Carboxypeptidase; Nasopharynx; Penicillin-Binding Proteins; Peptidyl Transferases; Polymerase Chain Reaction; Prevalence; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

The conventional therapeutic approach to bone infection associated with osteosynthesis is based on the idea that microbial eradication is most readily achieved by removal of the foreign material together with adequate antimicrobial therapy. This strategy usually requires implantation of external fixation devices with additional discomfort to the patient. We report our experience with conservative medical and antimicrobial therapy without removal of the osteosynthesis until adequate bone callus deposition is documented by bone radiography scan. Twenty patients with infections associated with intramedullary nailing (9 patients), screws and plate (9 patients) or screws (2 patients) were treated between 1995 to 2000. Osteosynthesis implantation sites were tibia (7 patients), femur (6 patients), femur and tibia (1 patient), humerus (1 patient), others (5 patients). Diagnosis of infection was based on clinical-microbiological evidence and confirmed by 99Tc-labeled leukocyte scan studies. Offending pathogens were Staphylococcus aureus 17 cases, Staphylococcus aureus + Escherichia coli, Staphylococcus epidermidis, unknown, 1 case each. Most infections were initially treated with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampin followed by oral antimicrobial therapy usually with ciprofloxacin or minocycline plus rifampin. Mean duration of antimicrobial therapy was 27.7 weeks (range 12-64 weeks). All patients (100%) were cured, and none complained of side-effects requiring antibiotic therapy discontinuation. We conclude that conservative medical therapy is feasible for osteosynthesis-associated bone infection.

Topics: Adolescent; Adult; Aged; Ciprofloxacin; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Follow-Up Studies; Fracture Fixation, Internal; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Wound Infection; Teicoplanin

We report the case of a 44-year-old obese diabetic woman admitted for fever. Blood cultures grew Staphylococcus Aureus and antibiotherapy was started. Iliac abscess was diagnosed and surgical drainage done. Clinical evolution was marked by metastatic dissemination: sacroiliac osteolysis, right shoulder osteoarthritis, spondylitis of the third lumbar vertebra and pulmonary localizations. This case-report shows diagnosis and treatment difficulties of an iliac muscle abscess with metastatic localization in a diabetic patient.

Topics: Abscess; Adult; Anti-Bacterial Agents; Diabetes Complications; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Obesity; Rifampin; Staphylococcal Infections; Treatment Outcome

Because bacterial colonization of medical devices may result in clinical infection, it is conceivable that antimicrobial impregnation of tissue expanders may reduce the rate of infection. The objective of this in vitro study was to examine the spectrum, durability, and shelf-life antimicrobial activity of minocycline/rifampin-impregnated silicone tissue expander shells. The impregnated devices exhibited zones of inhibition at baseline against Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli. The impregnated devices exhibited strong residual activity against S. epidermidis and S. aureus after suspension in serum at 37 degrees C for 4 weeks. There was no significant decrease in the size of zones of inhibition after storing the impregnated devices at room temperature for 1 year. These results indicate that minocycline/rifampin-impregnated tissue expander shells provide broad-spectrum and durable antimicrobial activity and that the shelf-life antimicrobial activity exceeds 1 year. These findings prompt future exploration of the anti-infective efficacy of these antimicrobial-impregnated devices.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibiotics, Antitubercular; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Minocycline; Prosthesis-Related Infections; Rifampin; Silicones; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Tissue Expansion Devices

The emergence and spread of multiresistant methicillin-resistant Staphylococcus aureus (MRSA) strains, especially those resistant to fusidic acid and rifampicin, in Malaysian hospitals is of concern. In this study DNA fingerprinting by PFGE was performed on fusidic acid- and rifampicin-resistant isolates from Malaysian hospitals to determine the genetic relatedness of these isolates and their relationship with the endemic MRSA strains. In all, 32 of 640 MRSA isolates from 9 Malaysian hospitals were resistant to fusidic acid and rifampicin. Seven PFGE types (A, ZC, ZI, ZJ, ZK, ZL and ZM) were observed. The commonest type was type ZC, seen in 72% of isolates followed by type A, seen in 13%. Each of the other types (ZI, ZJ, ZK, ZL and ZM) was observed in a single isolate. Each type, even the commonest, was found in only one hospital. This suggests that the resistant strains had arisen from individual MRSA strains in each hospital and not as a result of the transmission of a common clone.

Topics: Anti-Bacterial Agents; DNA Fingerprinting; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Fusidic Acid; Humans; Malaysia; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Antibiotics, Antitubercular; Coagulase; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Meningitis, Bacterial; Rifampin; Staphylococcal Infections; Staphylococcus; Treatment Outcome; Vancomycin

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.

Topics: Anti-Bacterial Agents; Bacteremia; Clindamycin; Cross Infection; Erythromycin; Gentamicins; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin; Virginiamycin

To assess, in an animal study, the efficacy of minocycline/rifampin-impregnated silicone sections of pump bulbs from penile implants in preventing device colonization by Staphylococcus aureus. Infection constitutes a very serious complication of penile implants.. Minocycline/rifampin-impregnated and control silicone pump bulb sections from penile implants were each inoculated with about 10(3) to 10(4) colony-forming units of S. aureus. After 8 hours of incubation with bacteria at room temperature, the test devices were allowed to dry for 30 minutes, and then subcutaneously implanted in the backs of rabbits. Eleven rabbits each received a total of six devices. The wounds were sutured, and the rabbits were monitored daily, then killed at 2 days after surgery. In vitro zones of inhibition against S. aureus by the minocycline/rifampin-impregnated and control devices were also determined.. All of the six tested antimicrobial-impregnated devices but none of the control devices produced zones of inhibition in vitro against S. aureus (mean zone of inhibition by antimicrobial-impregnated devices of 23 mm). The antimicrobial-impregnated devices retrieved from rabbits were sixfold less likely than were the control devices to be colonized with S. aureus (2 [6%] of 33 versus 11 [33%] of 33, respectively; P = 0.011).. The results of this animal study indicate that minocycline/rifampin-impregnated pump bulb sections from penile implants provide antimicrobial activity in vitro against S. aureus and protect against staphylococcal colonization of devices implanted for 2 days in animals.

Topics: Animals; Anti-Bacterial Agents; Female; Minocycline; Penile Prosthesis; Prosthesis-Related Infections; Rabbits; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus

to determine if local, in addition to systemic antibiotic prophylaxis (compared to that provided by systemic prophylaxis alone) provides additional benefit in terms of reducing graft infection.. gelatin-sealed Dacron grafts were interposed in the infrarenal aorta of 36 mongrels and inoculated with 1 ml of a S. aureus suspension. Group 1 (control group) received no prophylaxis and were inoculated with 1 ml containing 10(9)cfu/ml. Group 2 (n=6) received systemic prophylaxis (1 g cephamandole) and were inoculated with 10(5) cfu/ml (n=3) or 10(7) cfu/ml (n=3). Group 3 received systemic prophylaxis (1 g cephamandole) and were inoculated with 109 cfu/ml. Group 4 received systemic prophylaxis (2 g cephamandole) and were inoculated with 10(9)cfu/ml. In group 5 and 6 grafts were soaked in a rifampicin solution before use and inoculated with 10(9) cfu/ml. Group 5 received no systemic prophylaxis and group 6 received systemic prophylaxis (1 g cephamandole). Grafts were harvested at 2 weeks, and peritonitis, perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken of the graft, the perigraft tissues and the peritoneal fluid. Graft segments were incubated in broth medium.. inoculation with 10(9) cfu/ml ensured graft infection. Systemic or local prophylaxis alone failed to prevent graft infection. Only systemic and local antibiotic prophylaxis provided significant better results than no prophylaxis at all (p<0.01) and local prophylaxis alone (p<0.05). However, total "graft sterility" was not achieved as bacteriologic analysis of the graft segments showed low bacterial counts (<10 bacteria/graft) in 5 of 6 grafts.. local and systemic prophylaxis provided more protection as demonstrated by the significant decrease in the incidence of "overt" graft infection. Total "graft sterility" cannot be expected in the case of an overwhelming bacterial challenge.

Topics: Animals; Antibiotic Prophylaxis; Aortic Valve; Autopsy; Disease Models, Animal; Dogs; Heart Valve Prosthesis; Models, Cardiovascular; Polyethylene Terephthalates; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

We compared the efficacies of quinupristin-dalfopristin (Q-D; 30 mg/kg of body weight every 8 h) and vancomycin (60 mg/kg twice daily), alone or in combination with rifampin (10 mg/kg twice daily), in a rabbit model of methicillin-resistant Staphylococcus aureus knee prosthesis infection. In contrast to vancomycin, Q-D significantly reduced the mean log(10) CFU per gram of bone versus that for the controls. The combination of rifampin with either Q-D or vancomycin was significantly more effective than monotherapy.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Synergism; Drug Therapy, Combination; Joint Prosthesis; Methicillin Resistance; Prosthesis-Related Infections; Rabbits; Rifampin; Staphylococcal Infections; Tissue Distribution; Vancomycin; Virginiamycin

A 10-year-old girl with chronic myelogenous leukemia began receiving cyclosporine the day before bone marrow transplant surgery Three days after the transplant, she developed fever and neutropenia due to a Staphylococcus aureus bacteremia. Despite treatment with various antibiotics, the patient's fever persisted over the next 4 days. Intravenous rifampin was added to her antibiotic regimen of piperacillin, tobramycin, cloxacillin, and amphotericin. On day 12, the patient's blood cultures were negative and her fever had resolved; rifampin was discontinued. On day 16, the patient engrafted; she subsequently developed a grade II graft-versus-host disease of the skin and gastrointestinal tract, which responded to methylprednisolone. Her cyclosporine blood levels, which had been subtherapeutic since day 5 despite increasing intravenous dosages, were within the therapeutic range on day 21, and she was discharged 12 days later. To our knowledge, this is the first documented case of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a child receiving a bone marrow transplant who subsequently developed acute graft-versus-host disease.

Topics: Antibiotics, Antitubercular; Bacteremia; Bone Marrow Transplantation; Child; Cyclosporine; Drug Interactions; Female; Fever; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infusions, Intravenous; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model.. Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone.. In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 +/- 0.3 mm, 36.0 +/- 0.2 mm, and 11.8 +/- 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 +/- 1.1 mm and 7.6 +/- 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 +/- 0.2 mm and 18.5 +/- 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitory concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection.. These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitory concentration MRSA strains or poor susceptibility.

Topics: Animals; Antibiotics, Antitubercular; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Dogs; Escherichia coli; Escherichia coli Infections; Gelatin; Methicillin Resistance; Microbial Sensitivity Tests; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Time Factors

The interest of the management of bone infections in the diabetic foot, inspired by the recommendations for the treatment of chronic osteitis, was assessed in this study.. Twenty bone infections in 17 diabetic patients with moderate to mild infections of the feet were confirmed by the results of X-ray and/or scintigraphic studies and bone surgery biopsy cultures revealing one or more bacteria sensitive to standard osteitis treatment (rifampicine + fluoroquinolone). The patients had received this treatment per os for a median duration of 6 months (3 to 10 months). Clinical follow-up was carried out during a consultation at 1, 3 and 6 months during treatment and then by telephone every six months after the end of treatment. Clinical success was defined as the disappearance of any local sign of infection and by the absence of relapse during the post-treatment follow-up period. The evolution of the bone infection was also assessed by the results of a control conducted 3 to 6 months after initiation of the antibiotic treatment.. At the end of the treatment, all signs of infection had disappeared in 15/17 patients (88.2%) and no relapse had occurred in 14 (82.3%) patients at the end of a median post-treatment period of 22 months (12 to 41 months). Resection of necrotic bone was performed at the same time as the bone biopsy in 2 patients. The median duration of hospitalisation was of 14 days (3 to 53 days). During the study, a multi-resistant germ was isolated in 4 patients (1 Pseudomonas aeruginosa, 3 Staphylococcus aureus). During the post-treatment follow-up, 3 patients dies from causes unrelated to the infection treated. No serious adverse event was reported during the study.. The results of this pilot study support the rationale of applying the treatment regimens of chronic osteitis to diabetic lesions of the feet, but are only applicable to comparable patients presenting with non-severe lesions of the feet. Moreover, the use of antibiotics with potent selection of resistance such as rifampicine and fluoroquinolone, requires that bone biopsies be taken, which is not easy in all the diabetic foot care centres. We are presently conducting a study to identify the sub-populations of diabetic patients who could benefit from such treatment.

Topics: Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Biopsy; Chronic Disease; Diabetic Foot; Drug Resistance, Multiple; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

The psoas abscess is a rare complication in obstetric and gynaecology. Two types of psoas abscess are recognized. The primary psoas abscess is generally following haematogenous dissemination of an infectious agent and the source is usually occult. The most frequently isolated pathogen is Staphylococcus aureus. On the other hand, the secondary abscess is the result of local extension of an infectious process near the psoas muscle. We report the case of a patient who develops a bacteremia from an infected cesarean section wound. The complications were thigh and psoas abscesses with left sacroiliitis. Medical management with prolonged antibiotherapy permit clinical, biological and radiological improvement. Although it required a long hospital stay, medical treatment alone was effective. More experience is required to determine which therapeutic option: medical treatment and/or surgery, is the best choice for this type of complication.

Topics: Adult; Bacteremia; Cesarean Section; Female; Fever; Humans; Klebsiella Infections; Klebsiella pneumoniae; Magnetic Resonance Imaging; Oxacillin; Penicillins; Pregnancy; Psoas Abscess; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tomography, X-Ray Computed

Bacterial colonization of mammary implants is a prelude to clinical infection and has been implicated in the etiology of capsular contracture. Antimicrobial impregnation of a variety of medical devices with the combination of minocycline and rifampin has recently emerged as a potentially effective method for preventing device colonization and device-related infection. The objective of this animal study was to examine in vivo the antimicrobial efficacy of minocycline/rifampin-impregnated, saline-filled silicone implants. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously placed implants was used. A total of 48 saline-filled silicone implants (24 antimicrobe-impregnated and 24 control unimpregnated implants) were suspended in a 106 colony-forming units/ml bacterial suspension of S. aureus for 30 minutes at room temperature, allowed to dry for 60 minutes, and then implanted subcutaneously in the back of 12 rabbits (two antimicrobe-impregnated and two control implants were placed in each rabbit). Rabbits were monitored daily, then killed either at 2 weeks (10 rabbits) or at 4 weeks (two rabbits) and cultured. The antimicrobe-impregnated implants were 12 times less likely to be colonized than control unimpregnated implants (two of 24 versus 23 of 24; p < 0.001), and they were a significantly less likely cause of implant-related infection (0 of 24 versus 22 of 24; p < 0.001) and implant-related abscess (0 of 24 versus 21 of 24; p < 0.001) than control implants. The minocycline/rifampin-impregnated implants routinely demonstrated zones of inhibition against S. aureus at the time of explantation. These results indicate that minocycline/rifampin-impregnated implants can significantly decrease the rate of bacterial colonization, implant-related infection, and implant-related abscess. Antimicrobe-impregnated implants also have the potential of reducing the likelihood of capsular contracture.

Topics: Animals; Breast Implants; Female; Minocycline; Prosthesis-Related Infections; Rabbits; Rifampin; Silicones; Specific Pathogen-Free Organisms; Staphylococcal Infections

The purpose of this study was to compare the efficacy of rifampin-bonded gelatin-sealed and silver acetate/collagen-coated knitted polyester prostheses for the prevention of bacteremic graft infection in an animal model.. Eighteen 6.0-mm polyester grafts (length, 5.0 cm) were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into four groups as a function of type of prosthesis implanted. The dogs in groups I (n = 3) and II (n = 3) received control gelatin-sealed or collagen-coated polyester prostheses, respectively. In group III (n = 6), the dogs received rifampin-bonded gelatin-sealed polyester prostheses. In group IV (n = 6), the dogs received silver/collagen-coated polyester prostheses. Two days after implantation, the grafts were challenged with 6 x 10(9) Staphylococcus aureus intravenously. One week after implantation, the grafts were harvested with sterile technique. Quantitative cultures were obtained from all the harvested grafts. The results were expressed as colony-forming units per cm(2) of graft material. Bacteriologic study was also performed on various tissue samples. The chi(2) test was used to compare the culture proven infection of control and antimicrobial grafts.. All the control grafts were infected with S aureus at the time of removal. Five of the six silver/collagen-coated grafts were infected, whereas none of the six rifampin-bonded gelatin-sealed grafts grew S aureus (P <.01). There was no significant difference in the number of positive culture results of organ samples between the different groups of dogs.. These results indicate that rifampin-bonded gelatin-sealed polyester grafts are significantly more resistant to bacteremic infection than are silver/collagen-coated polyester grafts in a highly challenging model.

Topics: Acetates; Animals; Biocompatible Materials; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Dogs; Polyesters; Prosthesis-Related Infections; Rifampin; Silver Compounds; Staphylococcal Infections

Topics: Anti-Infective Agents; Arthritis, Infectious; Cefazolin; Cephalosporins; Drug Therapy, Combination; Fluoroquinolones; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Naphthyridines; Rifampin; Sacroiliac Joint; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim

Decolonisation of patients with urinary catheter colonisation by meticillin-resistant Staphylococcus aureus (MRSA) is often difficult. Replacement of the catheter after prophylactic vancomycin administration has been one approach that is often unsuccessful in clinical practice. We suspected that formation of MRSA biofilms might account for the persistence of infection, and our study confirms this, also showing that MRSA is able to colonise a silastic rubber surface even in the presence of prophylactic vancomycin or rifampicin.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Methicillin; Methicillin Resistance; Microscopy, Electron, Scanning; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 microg/ml) and to Q-D (MICs, 0.5 to 1 microg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 microg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 microg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 microg/ml, respectively). In vitro time-kill curve studies showed an additive effect [corrected] between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Kinetics; Lincosamides; Macrolides; Microbial Sensitivity Tests; Mutation; Phenotype; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Virginiamycin

Topics: Adult; Aged; Clindamycin; Drug Therapy, Combination; Female; Folliculitis; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Antibiotic Prophylaxis; Arthritis, Rheumatoid; Arthroplasty, Replacement, Knee; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Knee Joint; Middle Aged; Preoperative Care; Prosthesis Failure; Prosthesis-Related Infections; Recurrence; Reoperation; Rifampin; Staphylococcal Infections; Treatment Outcome; Vancomycin

We report a case of chronic wound infection (abscess, fistula) after a Lichtenstein repair of inguinal hernia. After surgical treatment (mesh explantation), a small-colony variant (SCV) of Staphylococcus aureus was cultured microbiologically. SCV represent subpopulations of Staphylococcus aureus which are associated with chronic infections and which respond poorly to usual treatment regimes. In this case surgery and specific antibiotic treatment with flucloxacillin and rifampicin were successful.

Topics: Abscess; Chronic Disease; Combined Modality Therapy; Cutaneous Fistula; Floxacillin; Hernia, Inguinal; Humans; Male; Middle Aged; Postoperative Complications; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection

Infection following total joint replacement remains a problem that has not been solved so far. The treatment options include removal of the implant and a delayed reconstruction or a direct exchange operation. Among patients with stable implants and short duration of infection as well as in patients who for certain reasons are inoperable, antibiotic therapy with a combination of rifampicin-ciprofloxacin may be a reasonable treatment option for curing staphyloccocal infection without removal of the implant. A case study of a Staphylococcus epidermidis (coagulase-negative) infection following delayed revision total knee replacement after septic loosening of a knee arthroplasty and its successful conservative treatment with rifampicin-ciprofloxacin is described. Alternative rifampicin combinations are discussed with respect to recently developed pharmacodynamical and pharmacokinetical findings of biofilm active drugs.

Topics: Anti-Bacterial Agents; Blood Sedimentation; C-Reactive Protein; Ciprofloxacin; Debridement; Drug Therapy, Combination; Humans; Knee Prosthesis; Male; Middle Aged; Prosthesis Failure; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infections. The effect of mupirocin-soaked Dacron was compared with the effect of rifampin-soaked, collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus. Graft infections were established in the back subcutaneous tissue of 195 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses followed by topical inoculation with 5 x 10(7) colony-forming units of S. aureus. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups in which perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg) was administered, four contaminated groups that received mupirocin- or rifampin-soaked graft, and four contaminated groups that received mupirocin- or rifampin-soaked graft and perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg). The grafts were sterilely removed 7 days after implantation and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed that the efficacy of mupirocin against both strains was significantly different from that of the untreated control. In addition, mupirocin was more effective than rifampin against the methicillin-resistant strain. Finally, only the combination of mupirocin and amoxicillin clavulanate produced complete suppression of growth of all strains.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Vessel Prosthesis; Collagen; Drug Therapy, Combination; Male; Methicillin Resistance; Mupirocin; Polyethylene Terephthalates; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus

In situ prosthetic graft replacement (ISPGR) of an infected prosthesis raises the risk of recurrent infection in the new graft, especially in cases involving drug-resistant microorganisms. The purpose of this animal study was to evaluate in situ replacement of a vascular graft infected by a highly rifampin-resistant strain of Staphylococcus epidermidis with the use of a rifampin-bonded polyester graft. Antibiotic bonding was obtained by soaking grafts in a high dose of rifampin solution (60 mg/mL). The infrarenal abdominal aorta of 20 dogs was replaced using a polyester prosthesis infected with a highly rifampin-resistant strain of Staphylococcus epidermidis. One week later, the 18 surviving animals were randomized into three groups. Group I (n = 6) did not undergo reoperation. Group II (n = 6) underwent ISPGR using a rifampin-bonded prosthesis. Group III (n = 6) underwent ISPGR using an untreated prosthesis. All surviving animals were killed 28 days after the first procedure. Infectious signs were noted and bacteriological study was carried out on explanted prostheses and various tissue samples. The findings of this experimental study show that soaking a polyester prosthesis in a high-dose rifampin solution can prevent reinfection after in situ replacement of a prosthesis infected by a highly rifampin-resistant Staphylococcus epidermidis.

Topics: Anastomosis, Surgical; Animals; Antibiotics, Antitubercular; Disease Models, Animal; Dogs; Female; Polyesters; Prosthesis Implantation; Random Allocation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Surgical Wound Infection; Survival Analysis; Time Factors; Treatment Outcome; Vascular Surgical Procedures

A patient being treated for sickle cell crisis developed swollen, painful, indurated, discoloured thighs after several days in hospital. Imaging revealed the presence of multiple small abscesses in the muscle and methicillin resistant Staphylococcus aureus (MRSA) was cultured from aspirated fluid. Pyomyositis usually occurs in association with damaged muscle and impaired host defences. Staphylococcus is the most frequent organism involved. It is not a common complication of sickle cell disease, although it may be under diagnosed. Availability of advanced imaging techniques facilitates early diagnosis of pyomyositis.

Topics: Adult; Anemia, Sickle Cell; Female; Fusidic Acid; Humans; Leg; Magnetic Resonance Imaging; Methicillin Resistance; Myositis; Rifampin; Staphylococcal Infections; Staphylococcus aureus

A rat model was used to investigate the efficacy of levofloxacin, cefazolin and teicoplanin in the prevention of vascular prosthetic graft infection. Graft infections were established in the subcutaneous tissue of 300 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis (10 mg/kg), two contaminated groups with intraperitoneal cefazolin prophylaxis (30 mg/kg), two contaminated groups with intraperitoneal teicoplanin prophylaxis (10 mg/kg) and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or te- icoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. The efficacy of levofloxacin against the methicillin- susceptible strain did not differ from that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The levofloxacin-rifampin combination proved to be similarly effective to the rifampin-teicoplanin combination and more effective than the rifampin-cefazolin combination against both strains. The rifampin-levofloxacin combination may be useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis because it takes advantage of the good anti-staphylococcal activity of both drugs.

Topics: Animals; Blood Vessel Prosthesis Implantation; Cefazolin; Drug Evaluation, Preclinical; Drug Implants; Drug Resistance; Drug Therapy, Combination; Injections, Intraperitoneal; Levofloxacin; Male; Methicillin Resistance; Models, Animal; Ofloxacin; Oxacillin; Premedication; Prostheses and Implants; Prosthesis-Related Infections; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin

Infection continues to be one of the major complications of cerebrospinal fluid (CSF) shunting procedures, and is caused mainly by skin-derived bacteria. Production of an extracellular biofilm plays an important role in the pathogenesis of shunt-associated infections by protecting bacteria from immune mechanisms and antibiotics. So far, removal of the original shunt and implantation of a new shunting device has been the only successful treatment for most patients. As an alternative strategy to prevent CSF infections, a rifampin-impregnated silicone catheter was designed to provide high initial and long-lasting (>60 days) release of bactericidal drug. To investigate the pathophysiological mechanism of its function, this new device was investigated both in vitro and in a rodent model of CSF infection by scanning electron microscopy (SEM) and bacterial culture. Staphylococcus epidermidis (10(8) cfu/ml) and S. aureus (10(4) cfu/ml) served as test strains. SEM demonstrated that, in contrast to the unloaded catheters, initial bacterial adherence on the catheter surface could be reduced to a few single cells, which did not show visible signs of proliferation. Bacterial cultures obtained simultaneously were all sterile, showing that adherent bacteria were killed immediately by the rifampin released from the catheter. Although rifampin incorporation into silicone polymers was not able to prevent initial bacterial adhesion completely, subsequent colonisation could be prevented.

Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Infections; Biofilms; Catheters, Indwelling; Cerebrospinal Fluid Shunts; Microscopy, Electron, Scanning; Rabbits; Random Allocation; Rifampin; Silicone Elastomers; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

The aim of this study was to treat methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis prosthetic vascular graft infections by in situ replacement with a rifampicin bonded Gelsoft graft.. Interposition grafts were placed in the carotid artery of 56 sheep and the graft surface directly inoculated with 10(8) colony forming units of MRSA or S. epidermidis. At three weeks, grafts were harvested and sheep allocated to three groups. In the MRSA group, sheep received grafts soaked in 1.2 mg/ml (12), 10 mg/ml (10) and no rifampicin (7). For S. epidermidis, sheep received grafts soaked in 1.2 mg/ml (10), 10 mg/ml (9) and no rifampicin (8). There were two deaths, in the MRSA study group. Remaining sheep were euthanased and grafts harvested three weeks following regrafting. Swabs were taken to assess bacterial growth in the perigraft tissues, and external and internal graft surfaces. A 3-5 mm segment of graft was incubated in broth medium.. For MRSA, no statistical difference between the groups was reached for any of the measured parameters. For S. epidermidis, a significant reduction was reached for total infected specimens in the 10 mg/ml group compared to both control (p<0.001) and 1.2 mg/ml (p<0.005) groups. Graft re-infection was also less likely to occur with S. epidermidis than MRSA.. Replacement of S. epidermidis infected vascular grafts with 10 mg/ml rifampicin soaked Gelsoft graft is effective in reducing subsequent S. epidermidis infection. This conclusion cannot be extended to MRSA infected vascular grafts.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Carotid Artery, Common; Female; Gelatin; Methicillin Resistance; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Reoperation; Rifampin; Sheep; Staphylococcal Infections; Staphylococcus epidermidis

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Cephalexin; Cephalosporins; Child; Female; Humans; Immunocompromised Host; Lymph Nodes; Pathology; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Recent case reports of vancomycin treatment failures in the United States, Japan, and France have prompted a retrospective analysis of 42 cases of septicemia caused by epidemic methicillin-resistant Staphylococcus aureus strain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicillin-resistant S. aureus in the United Kingdom; all cases occurred in a teaching hospital in Manchester, United Kingdom, between 1994 and 1998. Mortality was lowest (4%) in patients with rifampin-susceptible isolates treated with vancomycin and rifampin. It rose to 38% in patients who were treated with both antibiotics but in whom the organism became resistant to rifampin during therapy, and it reached 78% in patients who had rifampin-resistant isolates or in whom rifampin was contraindicated (P<.0001; Fisher exact test, 2-tailed). All isolates were susceptible to vancomycin by conventional laboratory testing, but susceptibility was lost by growth in vancomycin in vitro, becoming resistant at a minimum inhibitory concentration of 8 mg/L. This was associated with accumulation of cell-wall material. The deoxyribonucleic acid fingerprint remained unchanged. This study suggests that rifampin played a key role in the prevention of deaths caused by an epidemic strain of methicillin-resistant S. aureus that readily gave rise to a subpopulation with reduced susceptibility to vancomycin.

Topics: Animals; Anti-Bacterial Agents; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Methicillin; Mice; Microbial Sensitivity Tests; Microscopy, Electron; Penicillins; Prevalence; Retrospective Studies; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Virulence

Topics: Adult; Anti-Bacterial Agents; Appendicitis; Drug Therapy, Combination; Enterocolitis; Humans; Male; Nafcillin; Neutropenia; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tibial Fractures

To investigate the efficacy of levofloxacin in the prevention of vascular prosthetic graft infection in a rat model.. Graft infections were established in the subcutaneous tissue of 225 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis, two contaminated groups with intraperitoneal cefazolin prophylaxis, two contaminated groups with intraperitoneal teicoplanin prophylaxis and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or teicoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture.. The efficacy of levofloxacin against the methicillin-susceptible strain was not different to that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The combination levofloxacin-rifampin demonstrated to be similarly effective to the combination rifampin-teicoplanin and more effective than the combination rifampin-cefazolin against both strains.. Rifampin-levofloxacin combination seems useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis.

Topics: Animals; Blood Vessel Prosthesis; Humans; Levofloxacin; Male; Methicillin Resistance; Microbial Sensitivity Tests; Ofloxacin; Prosthesis-Related Infections; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

To report a case of pill-induced esophagitis caused by oral rifampin.. English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles.. A large number of oral medications have been reported to cause pill-induced esophagitis. This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture.. Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients. Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications.

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Endocarditis, Bacterial; Esophagitis; Heart Valve Prosthesis Implantation; Humans; Male; MEDLINE; Mitral Valve; Postoperative Complications; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tablets

This study examines the efficacy of the bonding of rifampicin, vancomycin or gentamicin to gelatin-coated knitted polymer meshes to prevent perioperative infection. Antibiotic bonding was obtained by soaking the meshes for 15 min in a solution containing 20 mg ml(-1) of rifampicin or 10 mg ml(-1) of vancomycin or gentamicin. A polymer mesh was implanted in a subcutaneous pouch in 16 rabbits: four received a rifampicin-soaked mesh, four received a vancomycin-soaked mesh, four received a gentamicin-soaked mesh, and four received an untreated mesh (control group). At the time of implantation, all the meshes were contaminated locally with 10(8) colony forming units of Staphylococcus aureus. Meshes were harvested one week later and submitted to bacterial counts. At the time of explantation, none of the antibiotic-soaked meshes were infected, whereas all the untreated meshes were infected. These results show that antibiotic soaking evidently prevents perioperative infection of gelatin-coated knitted polymer meshes in this model.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Coated Materials, Biocompatible; Colony Count, Microbial; Drug Delivery Systems; Female; Gelatin; Gentamicins; Implants, Experimental; Microbial Sensitivity Tests; Polymers; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Surgical Mesh; Vancomycin

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice daily), or parenteral nafcillin (30 mg/kg, four times daily). The left tibial metaphysis of New Zealand White rabbits was infected with Staphylococcus aureus. Grades 3 to 4 osteomyelitis (according to the Cierny-Mader classification system) development in the rabbits was confirmed radiographically. After antibiotic therapy regimens of 28 days, all tibias from controls that were infected but left untreated (n = 10) revealed positive cultures for Staphylococcus aureus at a mean concentration of 2.8 x 10(4) colony forming units/g bone. The rifampin plus clarithromycin (n = 15) and rifampin plus azithromycin (n = 15) groups showed significantly lower percentages of positive Staphylococcus aureus infection (20% and 13.3%, respectively) and bacterial concentrations (3.5 x 10(1) and 1.75 x 10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the nafcillin plus rifampin treated group (n = 7) showed no detectable Staphylococcus aureus infection (significantly lower than controls). The differences observed for bone bacterial concentrations and sterilization percentages between the antibiotic treated groups were not statistically significant. Although fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents usually prescribed with rifampin, increasing resistance has been observed. Although macrolides traditionally are not used in the treatment of osteomyelitis, the results of this study indicate that azithromycin and clarithromycin may be attractive partners for rifampin for the treatment of Staphylococcus aureus osteomyelitis in humans.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Azithromycin; Biological Availability; Clarithromycin; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Nafcillin; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Tibia; Treatment Outcome

Prosthetic graft infection after aortic aneurysm surgery is a life-threatening complication. Treatment options include total graft excision and extra-anatomic bypass grafting or in situ replacement of the graft. The latter option is gaining increasing popularity, but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We performed a prospective nonrandomized study to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection.. In a 6-year period from January 1992 to December 1997, 11 patients (eight men, three women) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. The median age of the patients was 66 years (range, 49 to 78 years). Four patients had a hemorrhage from an aortoenteric fistula, three had a retroperitoneal abscess, two had graft occlusion, one had a perigraft collection shown by means of computed tomography, and one had a ruptured suprarenal false aneurysm. Organisms were cultured from 10 patients.. MRSA was isolated in two patients, both of whom had originally undergone repair of a ruptured abdominal aortic aneurysm. Two patients died (18.2%) within 30 days, and three patients (27.6%) had nonfatal complications (peritoneal candidiasis, transient renal impairment, and profound anorexia). Two patients died late in the follow-up period. Seven patients remain alive and clinically free of infection.. The long-term results after total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favorable. However, MRSA aortic graft infection appears to be associated with a poor prognosis.

Topics: Aged; Antibiotics, Antitubercular; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Female; Humans; Male; Methicillin Resistance; Prospective Studies; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

Topics: Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Femur; Humans; Male; Muscle, Skeletal; Myositis; Osteomyelitis; Recurrence; Rifampin; Staphylococcal Infections

A subcutaneous catheter model in the rat was developed that allowed the study of prevention and treatment strategies for foreign body infection. In contrast to earlier models, the foreign body was inoculated with a low inoculum of Staphylococcus epidermidis just before implantation, thus mimicking intraoperative contamination with skin flora. Reproducible infection of all catheters followed if no prophylaxis was given. However, foreign body infection could be prevented or treated with antibiotics such as teicoplanin, which was marginally effective, and rifampicin, which proved very effective.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Catheters, Indwelling; Disease Models, Animal; Foreign Bodies; Prosthesis-Related Infections; Rats; Rats, Inbred F344; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Chlortetracycline; Drug Resistance, Microbial; Folliculitis; Health Personnel; Humans; Male; Methicillin; Middle Aged; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The aim of this study was to treat methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis prosthetic vascular graft infections by in situ replacement with a rifampicin bonded Gelsoft graft.. Interposition grafts were placed in the internal carotid artery of 56 merino sheep and the graft surface directly inoculated with 10(8) colony forming units (CFU) of MRSA (29) or S. epidermidis (27). At three weeks, grafts were harvested and sheep allocated to three groups. In the MRSA infected group, sheep received grafts soaked in 1.2 mg/ml (12), 10 mg/ml (10) and no (7) rifampicin. For S. epidermidis, sheep received grafts soaked in 1.2 mg/ml (10), 10 mg/ml (9) and no (8) rifampicin. There were two deaths, in the MRSA study group, one each from the rifampicin treated groups. The remaining sheep were euthanased and grafts harvested three weeks following regrafting. Grafts at harvests were assessed for perigraft abscess formation, anastomotic disruption and graft thrombosis. Swabs were taken to assess bacterial growth in the perigraft tissues, and external and internal graft surfaces. A 3-5 mm segment of graft was incubated in a broth medium. For S. epidermidis the remainder of the graft was ground and then incubated in a broth medium.. For MRSA, no statistical difference between the groups was reached for any of the measured parameters. For S. epidermidis, a significant reduction was reached for total infected specimens in the 10 mg/ml group compared to both control (p<0.001) and 1.2 mg/ml (p<0.005) groups. Graft reinfection was also less likely to occur with S. epidermidis than MRSA.. In conclusion, replacement of S. epidermidis infected vascular grafts with 10 mg/ml rifampicin soaked Gelsoft graft is effective in reducing subsequent S. epidermidis infection. This conclusion cannot be extended to MRSA infected vascular grafts.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Carotid Artery, Common; Female; Gelatin; Methicillin Resistance; Polyethylene Terephthalates; Prosthesis-Related Infections; Rifampin; Sheep; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

The incidence of cutaneous bacterial infection after carbon dioxide (CO2 laser resurfacing is increasing. Patients with staphylococcal colonization of their anterior nares may be at greater risk for postoperative cutaneous colonization and/or infection, which can potentially cause scarring.. We present a case report of methicillin-resistant Staphylococcus aureus secondary infection of the skin after CO2 laser resurfacing. We discuss the possible etiologies of this patient's infection, her postoperative management, and preoperative suggestions for possibly preventing infection.. A 49-year-old woman was treated with CO2 laser resurfacing for moderate actinic damage and facial rhytides. She developed a cutaneous infection with methicillin-resistant S. aureus, which caused diffuse linear scarring on her cheeks and upper lip.. The patient was successfully treated with oral minocycline, rifampin, and topical mupiricin ointment to her cutaneous erosions.. We propose that it would be helpful for patients undergoing CO2 laser resurfacing to have their nares cultured to see if they are staphylococcal carriers. If a patient is found to be a carrier, mupiricin ointment can be used preoperatively treat to the nares, to help decrease the risk of infection of the skin from this potential source.

Topics: Dermatologic Surgical Procedures; Drug Therapy, Combination; Facial Dermatoses; Female; Humans; Laser Therapy; Methicillin Resistance; Middle Aged; Minocycline; Mupirocin; Rifampin; Skin Aging; Skin Diseases, Bacterial; Staphylococcal Infections; Staphylococcus aureus; Surgery, Plastic; Surgical Wound Infection

Changes in antibiotic susceptibility was evaluated in 77 consecutive nosocomial clinical isolates of Staphylococcus aureus collected from 1986 to 1994 at the Umberto I Polyclinic of the University of Rome (63 isolates) and from 7 other Roman hospitals (14 isolates). Oxacillin resistance in these isolates increased from 39% during the 1980s to 69% during the 1990s. Significant increases in resistance to ciprofloxacin, clindamycin and rifampicin were observed among oxacillin-resistant strains. No resistance to glycopeptides was observed although both teicoplanin and vancomycin had slightly reduced antistaphylococcal activity.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Clindamycin; Cross Infection; Drug Resistance, Microbial; Glycopeptides; Humans; Italy; Oxacillin; Penicillins; Rifampin; Serum Bactericidal Test; Staphylococcal Infections; Staphylococcus aureus

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Drug Interactions; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Virginiamycin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Therapy, Combination; Humans; Joint Prosthesis; Orthopedic Fixation Devices; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections

Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in teaching hospitals in eastern Australian states, with prevalence rates averaging 25-30% of all S. aureus. Between 1990 and 1995, 1467 non-duplicate MRSA isolates from clinically infected sites were tested in Sydney, Melbourne, and Brisbane as part of a national survey of staphylococcal susceptibility. We reviewed the differing evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid. Despite similarities in community and hospital antibiotic use and MRSA prevalence rates, trends in resistance to the oral antibiotics in these cities have progressed independently of each other. In the 1995 survey in individual hospitals in Melbourne, 16-24% of strains were ciprofloxacin-resistant, compared with 80-100% in Sydney and 30-44% in Brisbane. There was great diversity of phage type patterns for ciprofloxacin-resistant strains, suggesting heterogeneous development of resistance. Rifampicin resistance was more closely associated with distinct dominant epidemic phage types, common to institutions in the same city, but without spread to the other cites. Between 1990 and 1995, these comprised 30-60% of all MRSA in Brisbane, compared with 5-10% in Melbourne and < 25% in Sydney. Fusidic acid resistance was uncommon and sporadic (< 5%), and was distributed equally between methicillin-resistant and methicillin-susceptible strains. Resistance to the oral agents in MRSA is due to a complex mix of antibiotic selection pressures and cross-infection with local and epidemic strains in closely related institutions. Each of these mechanisms can predominate, dependent on local factors and the antibiotics used.

Topics: Anti-Bacterial Agents; Australia; Bacteriophage Typing; Ciprofloxacin; Drug Resistance, Multiple; Endemic Diseases; Fusidic Acid; Hospitals, Teaching; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Prevalence; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The purpose of this study was to determine if 10 mg/ml rifampicin bonded to gelatin-sealed Dacron (Gelsoft) reduced staphylococcal infection. Grafts soaked in rifampicin were interposed in the left carotid artery of 20 merino sheep and then inoculated with 10(8) colony-forming units of MRSA (10 sheep) or a slime producing Staphylococcus epidermidis (10 sheep). Grafts were harvested at 3 weeks, and perigraft abscess, anastomotic disruption and graft occlusion recorded. Swabs were taken to assess bacterial growth of the perigraft tissues, and external and internal graft surface. Grafts segments were incubated in broth medium. Results were compared with previously published results that used graft that were not soaked in rifampicin (control) and grafts soaked in 1.2 mg/ml rifampicin. A total of 4/50 cultures were positive and significantly reduced for S. epidermidis compared with the control group of 30/50 (P < 0.05) and the 1.2 mg/ml group of 13/45 (P < 0.05). For the methicillin resistant staphylococcus aureus (MRSA) group, 6/40 cultures were positive, which was significantly reduced compared with the control group (38/40, P < 0.05) and the 1.2-mg/ml group (19/32, P < 0.05). In conclusion an increased concentration of rifampicin significantly reduced the incidence of prosthetic vascular graft infection following a challenge of MRSA or S. epidermidis.

Topics: Animals; Antibiotics, Antitubercular; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Drug Delivery Systems; Gelatin; Methicillin Resistance; Polyethylene Terephthalates; Prosthesis-Related Infections; Rifampin; Sheep; Staphylococcal Infections

Endogenous endophthtalmitis is an intraocular infection of hematogenous origin.. It is generally a panuveitis that may be mixed-up with a non-infectious inflammatory disease, promoting delayed treatment and compromising the visual prognosis, as the visual loss rate reaches up to 37.5%. Antibiotherapy should be started immediately after bacteriological examinations and without waiting for vitrectomy. Identification of the causative microorganism is absolutely necessary. It may require aqueous or vitreous culture if cultures from other body fluids are negative and infection progresses. The most common infections are endocarditis and digestive and renal diseases. Virectomy is indicated for first line treatment of ocular abcess and improvement of antibiotic absorption. However, it may lead to retinal detachment. Vitrectomy is also indicated in case of unsuccessful therapy. To decrease the inflammatory reaction and risks of vitreous organization, local or systemic corticotherapy is prescribed after control of the infection.. Although rare, endogenous endophthalmitis should be diagnosed as it may be mixed-up with inflammatory uveitis, leading to inappropriate corticotherapy. Furthermore, antibiotherapy with good intraocular penetration should be started immediately, but it should be kept in mind that the functional prognosis is poor.

Topics: Aged; Amphotericin B; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Endophthalmitis; Flucytosine; Humans; Male; Middle Aged; Ofloxacin; Oxacillin; Rifampin; Staphylococcal Infections; Vitrectomy

Antimicrobial coating of medical devices has recently emerged as a potentially effective method for preventing device-related infections. The objective of this animal study was to examine in vivo the antimicrobial efficacy of prosthetic heart valve sewing ring fabric coated with: (i) silver; (ii) combined minocycline and rifampin (M/R); or (iii) combined chlorhexidine and chloroxylenol (CH/CX).. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously implanted fabric of prosthetic heart valve sewing rings was used. Following administration of anesthesia and preoperative antibiotic prophylaxis, 0.5 x 0.5 cm samples of fabric were placed subcutaneously into the back of rabbits. Each rabbit received a total of eight samples: (i) two uncoated; (ii) two silver-coated; (iii) two M/R-coated; and (iv) two CH/CX-coated. After injecting a bacterial inoculum of 2 x 10(5) c.f.u. of S. aureus onto each implanted sample, the wounds were sutured. Rabbits were monitored daily for one week, killed and the test fabrics removed and cultured.. Rates of device colonization, device-related infection and device-related abscess were similar between the uncoated and silver-coated devices. Devices coated with M/R were less likely to be colonized or cause device-related infection when compared with uncoated devices, and less likely to be associated with abscess formation than silver-coated devices. There was a tendency for CH/CX-coated devices to be less colonized than uncoated devices. Only M/R-coated and CH/CX-coated devices produced zones of inhibition in vitro. Implantation of M/R-coated and CH/CX-coated devices in rabbits did not result in detectable systemic concentrations of the antimicrobial coating agents. Colonization of antimicrobial-coated devices was not associated with resistant S. aureus isolates.. These results suggest that silver-coated sewing rings may not prove to be clinically anti-infective. In contrast, antimicrobial-coated sewing rings that produce effective zones of inhibition, particularly those coated with M/R, are likely to be clinically protective.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Bacterial Adhesion; Chlorhexidine; Coated Materials, Biocompatible; Colony Count, Microbial; Disease Models, Animal; Drug Combinations; Female; Heart Valve Prosthesis; Minocycline; Prosthesis Design; Prosthesis-Related Infections; Rabbits; Rifampin; Silver Sulfadiazine; Staphylococcal Infections

Antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. In case of foreign body infections, bacteria may multiply less optimally. We examined the effects of several classes of lipophilic antistaphylococcal agents to determine their antimicrobial activity towards coagulase-positive and coagulase-negative staphylococci during the non-growing and slowly growing phases. Only two-fold combinations containing rifampicin were bactericidal (3-log kill) against Staphylococcus aureus. This was in contrast to growing bacteria in the log phase, in which a variety of antibiotics produced relevant killing. Concerning the staphylococci examined, antibiotic killing was greatly dependent on the growth rate. Most of the two-fold combinations containing rifampicin showed additive and synergistic antibacterial activity both in growth and stationary states as measured by the killing kinetics. The theoretical and clinical implications of delayed killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampicin and a second lipophilic antistaphylococcal drug may be most promising and appropriate as coating substances for intravascular devices or for clinical application in cases of implant infections.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Erythromycin; Fusidic Acid; Humans; Microbial Sensitivity Tests; Mupirocin; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis

Oral therapy of staphylococcal infection of orthopaedic implants with 900 mg/day rifampicin combined with either 1.5 g/day fusidic acid for 5 days followed by 1 g/day thereafter, or 600 mg/day ofloxacin was compared. Patients with an infected hip were treated for 6 months, with removal of any unstable prosthesis after 5 months' treatment and those with an infected knee prosthesis were treated for 9 months, with removal of the prosthesis after 6 months of treatment. Patients with infections of other type of bone implants were treated for 6 months with removal of the implant after 3 months of treatment, if necessary. Cure was defined as the absence of clinical, microbiological and radiological evidence of infection 12 months after completion of treatment. The treatment of 46 of the 52 included in the study was evaluated for safety and that of 42 was assessed for efficacy. Overall treatment was successful for 11 (55%) of 20 patients treated with rifampicin and fusidic acid group and for 11 (50%) of the 22 treated with rifampicin and ofloxacin. Treatment failed in four cases in each treatment group because of persistent infection. One patient given rifampicin and fusidic acid and three patients given rifampicin and ofloxacin failed treatment because of relapse. Superinfection led to failure in the remainder and was due to staphylococci in all but one case in which Acinetobacter calcoaceticus var. anitratus was isolated. There were no side effects related to study treatment. Oral treatment with rifampicin combined with fusidic acid may be a suitable alternative to the combination of rifampicin and ofloxacin for treating implant infections due to Staphylococcus spp. either when the patient is intolerant to quinolones or when the infecting organism is resistant to these drugs.

Topics: Administration, Oral; Adult; Aged; Drug Therapy, Combination; Female; Fusidic Acid; Humans; Male; Middle Aged; Ofloxacin; Orthopedic Fixation Devices; Rifampin; Staphylococcal Infections

We studied the efficacies of ofloxacin, rifampin, and clindamycin in a Staphylococcus aureus abscess model and seven antimicrobial regimens in an intracellular killing assay. Ofloxacin plus rifampin was the most effective regimen in the abscess model, and rifampin and ofloxacin were the most active regimens in the intracellular killing assay.

Topics: Abscess; Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Clindamycin; Microbial Sensitivity Tests; Models, Biological; Ofloxacin; Rabbits; Rats; Rifampin; Staphylococcal Infections; Staphylococcus aureus

To evaluate the efficacy and safety of cotrimoxazol plus rifampicin in staphylococcal osteoarticular infection.. Open, non-comparative study of adult hospitalized patients with documented staphylococcal bone infection.. From Feb 1989 to Dec 1993 28 episodes of staphylococcal bone infection were treated in 14 men and 13 women; the mean age was 48 +/- 21 years (range, 11-84). They received cotrimoxazol (7 mg/kg/day of trimethoprim) plus rifampicin (600-1200 mg/day), both orally, every 8 to 12 h with a mean duration of treatment of 34.2 +/- 8.2 days (range, 21 to 55 days). This antibiotic regimen was initiated at the same time that appropriate surgery for each specific condition was undertaken. Diagnoses were postsurgical osteomyelitis (10 cases), infected total hip prostheses (4 cases, one with 2 episodes), osteomyelitis secondary to external pin fixation (5 cases), soft tissue infections linked to orthopedic implants (3 cases), two cases of metatarsal osteomyelitis (one diabetic foot and one patient with polineuropathy), and one case each of chronic osteomyelitis of femur, hematogenous lumbar spondylitis and posttraumatic osteomyelitis. Four patients had bacteremia. The duration of the infection, prior to surgery was less than one month in 12 episodes, 1 month to 2 years in 14, and in 2 cases, of 10 and 13 years, respectively. In 23 episodes the causal agent was Staphylococcus aureus and in 5 cases it was coagulase-negative staphylococci. Patients had received previous parenteral therapy with other antimicrobials during 2-40 days (X: 18.6 +/- 10.2 days). All patients but one had resolution of the infection and are currently asymptomatic 6 months to 5 years posttreatment in the 21 evaluable cases (X: 38 +/- 13.1 months). Five patients had adverse effects secondary to the antibiotic combination and in three these were severe enough to discontinue the antimicrobials. In no case of the 11 patients with post-treatment control cultures were staphylococci recovered from the wound.. The combination of cotrimoxazole plus rifampicin, both given orally, was highly effective in this selected group of patients. This combination should be considered as a useful alternative therapy of staphylococcal bone infection and deserves further study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Drug Therapy, Combination; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomyelitis; Postoperative Complications; Retrospective Studies; Rifampin; Spondylitis; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Mice were infected intravenously with rifampicin-resistant strains selected out of methicillin-resistant Staphylococcus aureus (MRSA) strains and examined for colonization of these organisms in the intestinal tract. Three of four MRSA strains colonized in the cecum of more than 80% of the mice inoculated with approximately 10(7) cfu/mouse. The extent of colonization paralleled the lethal activity, which was inversely related to the methicillin resistivity: moderately resistant strains (MIC: 12.5 micrograms/ml) tended to show more potent pathogenicity than highly resistant ones (MIC: > or = 100 micrograms/ml). Distribution and localization of the organisms in the mice infected with a moderately resistant and highly pathogenic strain S. aureus 1-6 RFPr were studied by autobacteriography. Within one day after infection, colonies of the infecting organisms were distributed all over the body and were especially dense in the liver and spleen. On day 3, the organisms in the liver and spleen disappeared, while many colonies were observed in the intestinal tract. The organisms in the intestinal tract remained for 14 days after infection. In the autobacteriograms of the mice infected with Escherichia coli KC-14 RFPr, such persistency in the intestinal tract was not demonstrated. When viable cell counts of the cecum contents of the mice infected with S. aureus 1-6 RFPr (approximately 10(7) cfu/mouse) were made, the organisms were detected as early as 3 hr after infection and then gradually increased to more than 4 logs cfu/g on day 7. With E. coli KC-14 RFPr, a few colonies were detected transiently in the cecum contents of mice at an early stage infection, but the organisms did not increase and disappeared by day 3 after infection. These results show that the colonization in the mouse intestinal tract is a specific phenomenon to the S. aureus species including MRSA strains.

Topics: Animals; Colony Count, Microbial; Digestive System; Drug Resistance, Microbial; Male; Methicillin Resistance; Mice; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Infection of an implantable cardioverter defibrillator developed 2 weeks after implantation, presenting with fever, swelling, redness, and tenderness of the skin above the generator site. A cloxacillin resistant coagulase-negative staphylococcus was repeatedly cultured from the abdominal wall pocket fluid. The infection was successfully treated with a combination of two antibiotics, fusidic acid and rifampin, given orally for 3 months. Although the device was not removed, infection did not recur during a 24-month follow-up.

Topics: Administration, Oral; Anti-Bacterial Agents; Defibrillators, Implantable; Drug Therapy, Combination; Fusidic Acid; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Tachycardia, Ventricular; Time Factors

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthrodesis; beta-Lactam Resistance; Hip Prosthesis; Humans; Joint Prosthesis; Knee Prosthesis; Osteomyelitis; Prognosis; Prospective Studies; Prosthesis-Related Infections; Reoperation; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Aged; Antibiotics, Antitubercular; Aorta, Abdominal; Blood Vessel Prosthesis; Drug Therapy, Combination; Female; Femoral Artery; Humans; Iliac Artery; Male; Oxacillin; Penicillins; Prosthesis Design; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections

To assess the changes in antibiotic resistances in Staphylococcus aureus, both methicillin-susceptible and methicillin-resistant strains, in Australia.. Retrospective review of data collected annually.. Twenty metropolitan teaching hospitals in the six States of Australia and the Australian Capital Territory from 1988 to 1994.. Changes in prevalence and resistance rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible strains, based on antibiotic susceptibility testing of clinical isolates of S. aureus.. Prevalence of MRSA has remained constant on the eastern seaboard of Australia. A distinctive strain of MRSA emerged in Western Australia which had different antimicrobial susceptibilities. Resistances emerged in MRSA strains from eastern Australia, principally to ciprofloxacin and rifampicin, while resistance to fusidic acid remained stable and resistance to chloramphenicol significantly declined. Resistances in methicillin-susceptible strains remained fairly stable, except for a decline in resistance levels for tetracycline. High levels of resistance were seen to penicillin, moderate levels to erythromycin and low levels to trimethoprim and fusidic acid in methicillin-susceptible strains.. The continued high prevalence of and increasing resistance in MRSA in some Australian hospitals have meant that some strains are now untreatable with oral antibiotics.

Topics: Australia; Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Hospitals, Teaching; Humans; Methicillin; Methicillin Resistance; Penicillins; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus

We report two pediatric patients with recalcitrant staphylococcal infections whose infections resolved when rifampin was added to standard antistaphylococcal therapy. One patient had a post-varicella staphylococcal ulcerative lesion and did not respond to cephalexin alone but did respond when rifampin was added. A second patient had staphylococcal bullous impetigo and did not respond to dicloxacillin or cephalexin but did respond when rifampin was added to the cephalexin. If a patient fails to respond to traditional antistaphylococcal therapy, the addition of rifampin may be beneficial.

Topics: Cephalexin; Chickenpox; Child; Drug Therapy, Combination; Hand Dermatoses; Humans; Impetigo; Male; Prospective Studies; Rifampin; Skin Diseases, Infectious; Skin Diseases, Vesiculobullous; Staphylococcal Infections; Wound Infection

To describe the diagnosis and management of bacterial pericarditis after heart transplantation.. Two patients with Staphylococcus aureus pericarditis after heart transplantation were successfully treated conservatively with closed catheter drainage and antibiotics.. The patients were alive three and six years, respectively, following surgery. At follow-up, right heart catheterization demonstrated normal hemodynamics in one patient and a pattern of constrictive pericarditis in the other patient which was man-aged with furosemide.. Conservative management of bacterial pericarditis by closed catheter drainage and antibiotics can be considered in selected patients after heart transplantation.

Topics: Adult; Anti-Bacterial Agents; Cardiac Catheterization; Cefazolin; Cloxacillin; Drainage; Heart Transplantation; Humans; Male; Middle Aged; Pericarditis; Postoperative Complications; Rifampin; Staphylococcal Infections

An animal model was used to assess the efficacy of rifampicin-impregnated, gelatin-sealed Dacron in the prevention of vascular graft infections caused by Staphylococcus epidermidis. Under a general anaesthetic an interposition graft was placed into sheep carotid artery. On completion of the operation 1 ml of normal saline containing 10(8) colony forming units (cfu) of a slime-producing S. epidermidis was inoculated directly onto the graft. After 3 weeks the graft was harvested. Swabs were taken of perigraft tissues, and of external and internal aspects of the graft. A 3-5-mm segment of the graft was incubated in broth medium and a second segment was ground for 5 min and incubated in broth medium. The presence of abscess formation and anastomotic disruption was assessed. Ten sheep received a gelatin-sealed Dacron graft (control), while nine received the same graft impregnated with rifampicin at a concentration of 1.2 mg/ml (treated). Eight of 10 control grafts were infected, with 30 of 50 possible cultures positive, compared with four of nine treatment grafts infected (P = 0.13) and 13 of 45 cultures positive (P = 0.004). The control group had four abscesses and two anastomotic disruptions; the treatment group had no abscesses (P = 0.05) or anastomotic disruptions (P = 0.26). Other organisms were isolated from nine of the 12 infected grafts, most commonly Staphylococcus aureus. There was no development of resistance to rifampicin. Rifampicin-impregnated, gelatin-sealed Dacron is successful at reducing the incidence of S. epidermidis vascular graft infection.

Topics: Administration, Topical; Animals; Antibiotic Prophylaxis; Bacteriological Techniques; Blood Vessel Prosthesis; Gelatin; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Sheep; Staphylococcal Infections; Staphylococcus epidermidis; Surface Properties

Treatment of mycotic aortic aneurysm by excision and extraanatomic bypass is difficult to apply when the infectious process involves the visceral arteries. On the basis of experimental studies in our laboratory that demonstrated prolonged antistaphylococcal activity of rifampin-bonded, gelatin-impregnated Dacron grafts after implantation in the arterial circulation, this conduit was successfully used for in situ replacement of a native aortic infection in two patients. Both patients had fever, leukocytosis, abdominal or back pain, and a computed tomographic scan that demonstrated contained rupture of a mycotic aneurysm. Preoperative computed tomography-guided aspiration and culture of periaortic fluid from one patient grew Staphylococcus aureus. Treatment consisted of prolonged (6 weeks) culture-specific parenteral antibiotic therapy, excision of involved aorta, oxychlorosene irrigation of the aortic bed, and restoration of aortic continuity by in situ prosthetic replacement. A preliminary right axillobifemoral bypass was performed in the patient who had an infection involving the suprarenal and infrarenal aorta. In both patients intraoperative culture of aorta wall recovered S. aureus. Patients were discharged at 20 and 21 days. Clinical follow-up and computed tomographic imaging of the replacement graft beyond 10 months after surgery demonstrated no signs of residual aortic infection. In the absence of gross pus and frank sepsis, the use of an antibiotic-bonded prosthetic graft with antistaphylococcal activity should be considered in patients who have arterial infections caused by S. aureus when excision and ex situ bypass are not feasible.

Topics: Aged; Aneurysm, Infected; Anti-Bacterial Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis; Female; Gelatin; Humans; Male; Polyethylene Terephthalates; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Vascular Surgical Procedures

A 71-year-old woman with active aortic prosthetic endocarditis due to Methicillin-resistant Staphylococcus epidermidis (MRSE) and subannular mycotic aneurysm and paravalvular leakage and acute mitral regurgitation underwent emergent surgical treatment. The mycotic aneurysm was closed using a prosthetic patch after surgical debridement. Re-aortic valve replacement with a 21-mm Hancock II prosthesis was performed at the paraannular position by utilizing the patch. Mitral valve was also replaced with a 27-mm Hancock II prosthesis. Antibiotic therapy was provided by vancomycin combined with rifampicin and gentamicin. The following regimen was given, vancomycin 1 g i.v. q12h for 6 weeks plus gentamicin 80 mg/day i.v. for 4 weeks plus rifampicin 450 mg/day orally for 6 weeks. Vancomycin and gentamicin doses were modified appropriately according to the monitored serum levels in the patient with renal failure. Postoperative course was uneventful. The patient is doing well 11 months after surgery and no recurrence of infection has been seen. We conclude that prompt surgical removal of the infected sources and appropriate antibiotic therapy based on the bacteriology may be the only curative treatment for uncontrolled infection at the active phase of MRSE prosthetic endocarditis.

Topics: Aged; Aneurysm, Infected; Anti-Bacterial Agents; Aortic Valve; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Gentamicins; Heart Valve Prosthesis; Humans; Macrolides; Methicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Treatment of orthopaedic device related infections with antibiotics alone generally has been thought to be inadequate. A rabbit model was used to compare the efficacy of 4 different antibiotic regimens for treating orthopaedic device related infection caused by slime producing Staphylococcus epidermidis. After bacterial inoculation of a hole drilled through the intercondylar notch, a stainless steel screw was placed into the femur. Two weeks later, rabbits were randomized to receive a 2-week course of antibiotics: (1) 9 rabbits received vancomycin alone; (2) 10 rabbits received minocycline alone; (3) 10 rabbits received vancomycin plus rifampin; and (4) 10 rabbits received minocycline plus rifampin. Quantitative bone cultures were performed, and antibiotic levels in serum, bone, and biofilm were determined. Despite high levels of vancomycin in biofilm, infection was never cured by vancomycin alone and was eradicated in only 20% of rabbits that received minocycline alone. The highest cure rate (90%) was achieved with the combination of vancomycin and rifampin, whereas the combination of minocycline and rifampin yielded a cure rate of 70%. These results encourage the clinical evaluation of the combination of vancomycin and rifampin in patients in whom infected orthopaedic device cannot be removed.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Minocycline; Prosthesis-Related Infections; Rabbits; Random Allocation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Bacteremia; Catheterization, Central Venous; Cefamandole; Cephalosporins; Ciprofloxacin; Clindamycin; Daptomycin; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Neoplasms; Novobiocin; Oxacillin; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin; Virginiamycin

Autobacteriography was proposed as a bacteriological method to follow distribution and localization of bacteria in experimentally infected animals. Infectious organisms were restricted to rifampicin-resistant strains to prevent contamination during autobacteriography. Mice were infected with Staphylococcus aureus Smith diffuse type RFPr (rifampicin-resistant) by the intravenous route and frozen at various intervals after infection. Whole body sections (40-microns thick) of the mice were transferred onto selective agar medium containing rifampicin to incubate at 37 degrees C. On day 1 after infection, dense colonies of the infecting organism on the sections were distributed in the whole body. On day 3, few organisms were detected in the liver and many were observed in the spleen, kidney and intestinal tract. On days 7, 14 and 21, the organisms in the liver and spleen disappeared, and those in the kidney and intestine remained. The remaining infectious organisms were demonstrated in the kidney and intestinal tract by autobacteriography of mice infected with S. aureus Smith compact type RFPr. By cultivation of the homogenate of the gastrointestinal tissues and their contents, the infectious organisms were detected mainly in the lower small intestines, cecum and large intestines.

Topics: Animals; Bacterial Translocation; Bacteriological Techniques; Disease Models, Animal; Drug Resistance, Microbial; Intestines; Male; Mice; Mice, Inbred Strains; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The efficacy of cefazolin or cefpirome alone or combined with rifampin was compared with that of vancomycin alone or combined with rifampin in an experimental model of methicillin-resistant, beta-lactamase-producing, coagulase-negative staphylococcal endocarditis. Phenotypically, the mecA gene-positive strain used in vivo did not exhibit methicillin resistance by the agar dilution or disk susceptibility method but was resistant in vitro (oxacillin MIC, 64 micrograms/ml) by the microtiter dilution method with 2% NaCl supplementation. Macrodilution broth susceptibilities of standard inocula failed to demonstrate cross-resistance of staphylococci to cefazolin (MIC, 8 micrograms/ml) or cefpirome (MIC, 4 micrograms/ml). In vivo, vancomycin and cefpirome had similar activities, and both regimens were more effective than was cefazolin alone. While the MIC of rifampin was low (0.031 micrograms/ml), monotherapy with rifampin resulted in a bimodal distribution of outcomes due to the expected emergence of resistant mutants. The results in vitro of time-kill synergy studies using rifampin in combination with cefazolin or cefpirome varied with the antimicrobial concentrations tested and did not reliably predict activities in vivo of rifampin-beta-lactam combination therapies. Cefpirome, but not cefazolin or vancomycin, in combination with rifampin was synergistic in vivo. Cefpirome in combination with rifampin was more effective than was cefazolin in combination with rifampin. Both cephalosporin-rifampin regimens were significantly more effective than was cephalosporin or vancomycin monotherapy and were as effective as vancomycin combined with rifampin. These data support further evaluation of rifampin-beta-lactam combinations as possible alternative therapies to vancomycin-containing regimens for selected methicillin-resistant coagulase-negative staphylococcal infections.

Topics: Animals; Antibiotics, Antitubercular; beta-Lactamases; Cephalosporins; Coagulase; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Methicillin Resistance; Microbial Sensitivity Tests; Phenotype; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Rifampicin impregnated Dacron grafts have been shown to be effective at preventing vascular graft infection in different animal models. The development of resistance to rifampicin would be a major drawback to the widespread use of such a graft. We aimed to determine how readily this would occur by using a sheep animal model.. Under general anaesthetic a 2cm long, 5mm diameter Dacron interposition graft inpregnated with 1.2 mg/ml rifampicin was placed in the left carotid artery. An extreme challenge of methicillin resistant Staphylococcus aureus (MRSA) using an inoculum of 10(9) colony forming units was placed directly onto the graft. The grafts were harvested at 3 weeks and cultures of the graft and tissues were taken. The presence or absence of any abscess formation, anastomotic disruption and graft thrombosis was noted. Any positive growths were identified and if found to be the same as the inoculum, the bacteria were used as the inoculum for another sheep. This was repeated once more. Thus we started with three sheep initially and used a total of nine sheep.. There were no deaths. All grafts were infected with the same MRSA strain, confirmed on phage typing. There were three abscess and one anastomotic disruption. Seven of the grafts were occluded. The minimal inhibitory concentration (MIC) of the infecting inoculum and the bacteria retrieved were determined using the agar dilutional method. The MIC for the three initial inocula was < 0.007 mg/l. All subsequent strains isolated had an MIC of < 0.015 mg/l. This was a difference of one dilution and not significant.. There was no development of rifampicin resistance using this animal model.

Topics: Animals; Blood Vessel Prosthesis; Drug Resistance, Microbial; Methicillin Resistance; Polyethylene Terephthalates; Prosthesis-Related Infections; Rifampin; Sheep; Staphylococcal Infections; Staphylococcus aureus

Ampicillin or amoxicillin at 625-800 mg/kg/day, in combination with a beta-lactamase inhibitor, each is as effective as vancomycin in animal models of methicillin-resistant Staphylococcus aureus endocarditis. Studies were done to determine whether the addition of rifampin would permit lowering the dose of ampicillin into the range recommended for use in humans without loss of efficacy. The efficacy of ampicillin/sulbactam (300/150 or 150/75 mg/kg/day intramuscularly, in three divided doses) in combination with rifampin (5 mg/kg intramuscularly, three times daily) was compared with that of vancomycin (25 mg/kg intravenously, twice daily, or 30 mg/kg intramuscularly, three times daily) in the rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Neither ampicillin/sulbactam nor rifampin alone was effective. The ampicillin/sulbactam/rifampin regimen was as effective as vancomycin. This regimen may be an alternative to vancomycin in treatment of methicillin-resistant S. aureus infections.

Topics: Ampicillin; Animals; Aortic Valve; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulbactam; Vancomycin

The affinity of rifampin to bond to Dacron permits implantation of a vascular prosthesis with anti-staphylococcal bioactivity. The performance of rifampin-bonded Dacron grafts was evaluated in vitro and in vivo to develop a bonding technique with optimal graft bioactivity which was then used for in situ reconstruction of a biofilm graft infection. In vitro bioactivity was measured at 24-hr intervals for three types of Dacron prostheses (plain, gelatin, and collagen-impregnated) exposed to rifampin at varied concentrations and immersion times. Gelatin-impregnated grafts demonstrated superior bioactivity (P < 0.05). Rifampin concentration and graft type had a greater effect on bioactivity than immersion time (P < 0.01). Gelatin-impregnated grafts immersed in a 60 mg/ml rifampin solution for 15 min produced optimum bioactivity. Six grafts prepared in this fashion were used to replace the canine aorta. The level and duration of in vivo antistaphylococcal activity to Staphylococcus aureus and Staphylococcus epidermidis were less (P < 0.05) than those measured in vitro, but rifampin levels exceeded the study strain maximum inhibitory concentration for up to 48 hr. In a canine model, the rifampin-bonded gelatin-impregnated (N = 14) or nonbonded control (N = 10) grafts were used as in situ replacement for an established aortic graft infection caused by S. epidermidis. Replacement with a rifampin-bonded graft resulted in successful anatomic healing of perigraft and anastomotic tissue. Persistent biofilm colonization was confirmed in 8 of 10 controls versus 4 of 14 rifampin-bonded grafts (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biofilms; Blood Vessel Prosthesis; Dogs; Female; Gelatin; Osmolar Concentration; Polyethylene Terephthalates; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Topics: Abscess; Cyclosporine; Cytochrome P-450 Enzyme System; Drug Interactions; Heart Transplantation; Humans; Mediastinal Diseases; Middle Aged; Rifampin; Staphylococcal Infections

Infection of cerebrospinal fluid (CSF) shunts is one of the major complications associated with their use and is usually managed by shunt removal, temporary insertion of an external drainage and implantation of a new shunt system. We have evaluated the efficacy of a rifampin-loaded silicone ventricular catheter to prevent bacterial colonization and infection in vitro and in an animal model. On the basis of an incorporation process a rifampin-loaded catheter was developed which is capable of releasing rifampin in bacteriocidal concentrations for 60 days and more. In a stationary bacterial adherence assay using S. epidermidis as test strain, the colonization resistance of the device was demonstrated. To assess the capability of the catheter to prevent CSF shunt infections, a rabbit model was developed which allowed the establishment of a reliable and reproducible CSF infection by implantation of silicone catheters into the ventricle and inoculating S. epidermidis (minimal dose 10(6) cfu) or S. aureus (minimal dose 10(3) cfu). Rifampin-loaded catheters (12 animals inoculated with S. epidermidis, 8 animals inoculated with S. aureus) were compared with non-loaded (14 animals inoculated with S. epidermidis, 19 animals inoculated with S. aureus) control catheters, and infection was documented by clinical, microbiological and histological methods. In contrast to the control group, none of the animals with rifampin-loaded catheters showed clinical signs of infection. Furthermore, in none of the materials obtained after sacrifice of the animals (catheter, brain tissue, CSF, blood) could the infecting bacteria be cultured, whereas in materials from animals with the unloaded catheter the infecting strains could always be cultured from the catheter and from surrounding brain tissue. The histological examination of catheter-adjacent tissue supported these findings. We conclude that a rifampin-loaded silicone ventricular catheter is capable of completely preventing bacterial colonization and infection by staphylococci as the main causative organisms in CSF shunt infections and should be further evaluated in clinical trials.

Topics: Animals; Catheters, Indwelling; Cerebrospinal Fluid Shunts; Colony Count, Microbial; Dose-Response Relationship, Drug; Equipment Design; Meningitis, Bacterial; Microbial Sensitivity Tests; Rabbits; Rifampin; Silicones; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentrations of bactericidal agents were compared with treatment outcomes of experimental infective endocarditis due to a methicillin-susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin combinations, in vitro synergy testing using recommended fractions of the MIC failed to predict antagonism in vivo while concentrations above the MIC corresponded with antagonism in vivo.

Topics: Animals; Cefazolin; Cefpirome; Cephalosporins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Microbial Sensitivity Tests; Nafcillin; Predictive Value of Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Bacteremia; Drug Resistance, Microbial; Humans; Male; Rifabutin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

The in vitro activity of vancomycin and teicoplanin (fourfold the MBC), alone and in combination with amikacin (16 mg/l) or rifampin (1 mg/l), against Staphylococcus epidermidis (slime-producing and non slime-producing strains) biofilms on different plastic catheters was evaluated. The addition of amikacin or rifampin significantly increased the activity of glycopeptides against sessile bacteria. With the slime-producing strain, these combinations were able to sterilize the surface of Vialon and polyvinylchloride catheters. It is concluded that the in vitro activity of glycopeptides against Staphylococcus epidermidis biofilms on plastic catheters can be increased by the addition of amikacin or rifampin.

Topics: Amikacin; Anti-Bacterial Agents; Biofilms; Catheters, Indwelling; Colony Count, Microbial; Drug Therapy, Combination; Humans; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin; Vancomycin

Topics: Animals; Biofilms; Blood Vessel Prosthesis; Combined Modality Therapy; Dogs; Humans; Models, Biological; Polyethylene Terephthalates; Prosthesis-Related Infections; Pseudomonas Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

The prophylactic and therapeutic activities of teicoplanin were evaluated in two different experimental models of foreign body infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected at a > 90% rate by 10(2) CFU of MRSA in control animals. A single dose of 30 mg of teicoplanin per kg of body weight administered intraperitoneally 6 h before bacterial challenge was as effective as vancomycin in preventing experimental infection in tissue cages injected with either 10(2), 10(3), or 10(4) CFU of MRSA. In a rat model evaluating the therapy of chronic tissue cage infection caused by MRSA, the efficacy of a 7-day high-dose (30 mg/kg once daily) regimen of teicoplanin was compared with that of vancomycin (50 mg/kg twice daily). Whereas high levels of teicoplanin were found in tissue cage fluid, continuously exceeding its MBC for MRSA by 8- to 16-fold, no significant reduction in the viable counts of MRSA occurred during therapy. In contrast, either vancomycin alone or a combined regimen of high-dose teicoplanin plus rifampin (25 mg/kg twice daily) could significantly decrease the viable counts in tissue cage fluids. Whereas the bacteria recovered from tissue cage fluids during therapy showed no evidence of teicoplanin resistance, they failed to be killed even by high levels of this antimicrobial agent. The altered susceptibility of in vivo growing bacteria to teicoplanin killing might in part explain the defective activity of this antimicrobial agent when used as monotherapy against chronic S. aureus infections. These data may indicate the need for a combined regimen of teicoplanin with other agents such as rifampin to optimize the therapy of severe staphylococcal infections.

Topics: Animals; Drug Resistance, Microbial; Drug Therapy, Combination; Foreign-Body Reaction; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Wistar; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

Implant-associated infections offer resistance to antibiotic treatment and possibly do so because the causative bacteria which reside on the artificial surface are enclosed in a protective matrix (biofilm) shielding the bacteria against the action of host defenses and antibiotic action. We have investigated in vitro the effect of various antimicrobial agents on biofilms of Staphylococcus epidermidis, which is the main organism responsible for implant-associated infections. Rifampin was found to exert superior activity, albeit incomplete, against S. epidermidis biofilms using an assay system which enabled the determination of the kinetics of antibiotic action over five days. In a large screening study looking for agents capable of completing the action of rifampin, gentamicin was unexpectedly found to be antagonistic to rifampin. The present study was undertaken to investigate further the activity of gentamicin and five other aminoglycoside antibiotics using a wider range of concentrations (2.5-20 micrograms/mL). The main findings were a marked synergy with rifampin demonstrated by streptomycin, producing a bactericidal outcome, which contrasted sharply with the indifference or antagonism shown by the other aminoglycosides. We then studied in further detail the effect of separate combinations of streptomycin and gentamicin with rifampin over a wider concentration range of each agent (1.25-40 micrograms/mL). Streptomycin showed strong rapid synergy with rifampin even at the lowest concentration of each antibiotic. Gentamicin demonstrated a concentration-related antagonism towards rifampin which was independent of rifampin concentration. The data support the conclusion that streptomycin, like cell-wall active antibiotics, exerts a potent synergy with rifampin against S. epidermidis biofilms, and that the other aminoglycosides, predominantly gentamicin, strongly antagonize rifampin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Bacterial Agents; Biofilms; Drug Interactions; Drug Therapy, Combination; Gentamicins; In Vitro Techniques; Prostheses and Implants; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Streptomycin

To identify factors associated with peritoneal dialysis-related infections at one center.. The study was a retrospective study of a 3-year time period with relatively stable treatment patterns.. A single center experienced academic peritoneal dialysis program.. Patients (N = 163) receiving peritoneal dialysis (PD) from January 1989 to December 1991 who had received treatment at home for at least one month.. None.. Catheter-related infection and peritonitis were the main outcome measures. Variables affecting infection rates that were assessed included age, time on PD, prior end-stage renal disease (ESRD) therapy, diabetic status, catheter type, exchange device, nasal carriage of S. aureus, and prophylactic rifampin therapy. Data were analyzed with univariate as well as with a fixed-effects and a mixed-effects gamma-Poisson multiple regression model.. Variables associated with an increased risk of new peritonitis included age under 20 years (p < 0.009; rate ratio 4.54) and nasal carriage of S. aureus (p < 0.04; rate ratio 1.75). Decreased new peritonitis risk was associated with the ULTRA Set exchange system (p < 0.008; risk ratio 0.38) and intermittent prophylactic rifampin therapy (p < 0.001; rate ratio 0.99 for each 1% time on therapy). Catheter-related infections were increased in patients who had double-cuff catheters (p < 0.003) and nasal carriage of S. aureus (p < 0.04; rate ratio 1.82). Decreased catheter-related infections were noted in older patients (p < 0.02; rate ratio 0.983/year) and increasing months of study follow-up (p < 0.03; rate ratio 0.97/month).. In our program nasal carriage of S. aureus increased the risk of peritonitis and catheter-related infection. Prophylactic rifampin significantly decreased peritonitis, as did use of the ULTRA Set. Single-cuff opaque catheters had the lowest catheter infection rate. Analysis of the relationships between clinical and demographic variables and peritoneal dialysis-related infection rate can identify significant contributing or protective variables and allow peritoneal dialysis programs to develop preventive strategies to minimize the risk of infection.

Topics: Catheters, Indwelling; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Nasal Mucosa; Peritoneal Dialysis; Peritonitis; Retrospective Studies; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus

The authors report the new protocol the apply for prevention of central venous catheter-related infections in haemodialysis. The used preparation is a combination of protamine sulphate and rifampicin and gives better results that povidone iodine in the same conditions.

Topics: Administration, Cutaneous; Antisepsis; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Drug Combinations; Equipment Contamination; Humans; Povidone-Iodine; Protamines; Renal Dialysis; Retrospective Studies; Rifampin; Skin; Staphylococcal Infections; Staphylococcus

The possibility of increasing the resistance of a synthetic vascular graft to intraoperative or immediate postoperative bacterial contamination justifies the interest in methods such as antibiotic bonding or antibiotic soaking. On the basis of this experience and with the aim of testing the efficacy of such a graft, a multicentre experimental study on sheep to compare the susceptibility to infection of Dacron Gelseal grafts (control) versus rifampicin-bonded Dacron Gelseal grafts (treated) following the intravenous infusion of 10(7)-10(8) cells Staphylococcus aureus was conducted. The grafts were implanted in both common carotid arteries of sheep. In a group of 11 animals (group A), a treated and a control graft were implanted in the same animal. In a group of four sheep (group B), only treated or control grafts were implanted in each animal. In group A, 36% of (four of 11) the treated grafts became infected versus 54% (six of 11) of the control prostheses. In group B, none of the treated grafts was infected by the inoculated pathogen, which, by contrast, infected 75% (three of four) of the controls. These observations confirm the recent interest aroused by the possibility of pretreating gelatin-coated Dacron grafts with rifampicin in the prevention of early graft infection.

Topics: Anastomosis, Surgical; Animals; Blood Vessel Prosthesis; Carotid Artery, Common; Equipment Contamination; Intraoperative Complications; Materials Testing; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Sheep; Staphylococcal Infections; Surface Properties; Survival Rate

The in vitro and in vivo antibacterial activities of the new rifamycin derivatives KRM-1648 and KRM-1657 were compared with those of rifampin. Rifabutin, ciprofloxacin, and clarithromycin were also tested for reference. The respective MICs of KRM-1648 and KRM-1657 for 90% of the strains tested (MIC90S) were 0.016 and 0.0078 microgram/ml, respectively, for methicillin-susceptible Staphylococcus aureus, 0.016 and 0.0039 microgram/ml, respectively, for methicillin-resistant S. aureus, and 0.0625 and 0.016 microgram/ml, respectively, for methicillin- and quinolone-resistant S. aureus. These MIC90S of KRM-1657 were equal to or 2- to 64-fold lower than those of rifampin. KRM-1648 and KRM-1657 with MIC90S of between 0.002 and 0.078 microgram/ml were 2- to 128-fold more active than rifampin against Staphylococcus epidermidis and Streptococcus species, including Streptococcus pneumoniae and Streptococcus pyogenes. The MIC90S of KRM-1657 for Haemophilus influenzae and Neisseria gonorrhoeae were 0.25 and 0.1 microgram/ml, respectively; KRM-1657 was almost as active as rifampin and was 8- to 16-fold more active than KRM-1648 against these strains. The frequency of occurrence of spontaneous mutations to resistance to KRM-1648 and KRM-1657 was equal to that to rifampin. Against systemic infection with S. aureus in mice, the efficacies of KRM-1648 and KRM-1657 were comparable to that of rifampin.

Topics: Animals; Antibiotics, Antitubercular; Bacteria; Bacterial Infections; Drug Resistance, Microbial; Male; Mice; Mice, Inbred ICR; Mutation; Rifampin; Rifamycins; Staphylococcal Infections; Staphylococcus aureus

A gelatin-sealed porous Dacron graft impregnated with rifampin was evaluated in a two-part study of its use in preventing prosthetic infection.. The graft was impregnated by soaking it for 15 minutes in rifampin (1 mg/ml). In part 1 its antibacterial activity and rifampin retention over time were determined. Infrarenal aortic replacement was performed in pigs, and the rifampin concentration of the graft, serum, and perigraft space was assayed up to 96 hours after surgery. In part 2, infection resistance was tested in pigs in which the retroperitoneum was contaminated with Staphylococcus aureus after graft replacement. The postoperative infection rate was compared in three groups: pigs given gelatin-sealed grafts without rifampin (controls), pigs receiving nonimpregnated grafts and intravenous rifampin (15 mg/kg) for 3 days after surgery, and those given the rifampin grafts.. Rifampin was present in the grafts for up to 72 hours after surgery and in the perigraft fluid for 24 hours but was never detected in the serum. The grafts had inhibitory activity in vitro against S. aureus and the biofilm phase of Staphylococcus epidermidis for up to 3 days and against Escherichia coli for 2 days. Pigs given intravenous rifampin had a significantly lower infection rate than had control pigs (7/12 vs 13/13; p = 0.02); those receiving the rifampin graft had a lower rate (2/13) than had either the control pigs (p < 0.001) or those given intravenous rifampin (p < 0.04).. This simple method of graft impregnation resulted in antibiotic retention for 3 days and appeared to be superior to intravenous antibiotic administration in preventing perioperative graft infection.

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Escherichia coli Infections; Gelatin; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Swine; Time Factors

The purpose of this study was to treat an established prosthetic vascular graft infection by in situ replacement with a rifampin-bonded gelatin-sealed Dacron graft in an animal model.. The infrarenal aorta of 18 dogs was replaced with a gelatin-sealed graft contaminated in vitro by soaking it in a solution with Staphylococcus epidermidis. One week later, animals were randomized into three groups. In group I (control, (n = 6), the dogs did not undergo repeat operations. The dogs in groups II and III underwent repeat operation. In these animals the infected grafts were removed for bacteriologic analysis and replaced in situ with one of two types of grafts: group II (n = 6) received an untreated, gelatin-sealed graft; group III (n = 6) received a rifampin-bonded, gelatin-sealed graft. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 60 mg/ml saline solution of rifampin at 37 degrees C. All 18 dogs received no systemic adjunct antibiotic therapy. Control grafts and replacement grafts were removed 4 weeks after the initial implantation for bacteriologic analysis. When harvested, all the grafts were cut into two fragments, and quantitative bacterial cultures were obtained from all the fragments. Results were expressed as colony-forming units (CFU)/cm2 of graft material.. All 18 initially implanted grafts and all the untreated replacement grafts were grossly infected at the time of removal, whereas all the rifampin-bonded replacement grafts had normal incorporation. None of the rifampin-bonded grafts grew bacteria, whereas all the initially implanted and all the untreated replacement grafts were infected (p < 0.01). Bacterial counts from the infected fragments were similar in control grafts (2.6 +/- 1.9 x 10(6) CFU/cm2), in initially implanted grafts of groups II (9 +/- 1.1 x 10(5) CFU/cm2) and III (1.3 +/- 1.5 x 10(6) CFU/cm2), and in untreated replacement grafts of group II (1.7 +/- 2.5 x 10(6) CFU/cm2). Blood culture results and culture results of liver, spleen, kidney, and lung specimens at the time of sacrifice were negative.. This study demonstrates that rifampin-bonded gelatin-sealed Dacron grafts are resistant to infection when used for in situ replacement of an infected graft in the dog.

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Colony Count, Microbial; Dogs; Female; Gelatin; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Following cardiac transplantation bacterial mediastinitis is a severe early complication. Between March 1986 and September 1993, cardiac transplant operations were performed in 101 patients, of whom six developed purulent mediastinitis. Treatment consisted of surgical débridement, closed local irrigation, drainage and systemic antibiotics. No patient died as a result of bacterial mediastinitis. Low cardiac output and requirements for resternotomy for bleeding and prolonged artificial ventilation were significantly higher in the group with sternal infection. In contrast, since January 1991 the dose of corticosteroid was decreased from 5 mg/kg per day to 1.5 mg/kg per day beginning on the first day after operation. A total of 51 heart transplant operations have been subsequently performed without sign of mediastinal infection.

Topics: Adult; Bacterial Infections; Combined Modality Therapy; Debridement; Dose-Response Relationship, Drug; Enterococcus; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Mediastinitis; Middle Aged; Postoperative Complications; Povidone-Iodine; Reoperation; Rifampin; Serratia Infections; Staphylococcal Infections; Surgical Wound Infection; Therapeutic Irrigation

Using an equilibrium dialysis chamber, we evaluated the penetration of vancomycin, rifampin, or both through a staphylococcal biofilm to simulate treatment of an infected biomedical implant. A biofilm of ATCC 35984 (slime-positive Staphylococcus epidermidis; vancomycin MIC and MBC, 1 and 2 micrograms/ml, respectively; rifampin MIC and MBC, 0.00003 and 0.00025 micrograms/ml, respectively) was established on the inner aspect of the dialysis membrane (molecular mass exclusion, 6,000 kDa). Serum containing vancomycin (40 micrograms/ml), rifampin (20 micrograms/ml), or a combination of both was introduced into the inner chamber of the dialysis unit (in direct contact with the biofilm), and serum alone was added to the outer chamber. Rifampin and vancomycin concentrations in both chambers were determined over a 72-h period. In the absence of rifampin, the concentration of vancomycin in the outer chamber exceeded the MBC for the organism after 24 h, and the MBC increased to nearly 8.0 micrograms/ml by 72 h, demonstrating that therapeutic levels of vancomycin can penetrate a staphylococcal biofilm. However, viable bacteria were recovered from the biofilm after 72 h of treatment with no apparent increase in the MIC or MBC of vancomycin. Similarly, concentrations of rifampin exceeding the MBC were detected in the outer chamber after 24 h of treatment, but viable organisms were recovered from the biofilm after 72 h of treatment. In this case, the rifampin MBCs for surviving organisms increased from 0.00025 to > 128 micrograms/ml. The combination of agents prevented the development of resistance to rifampin, improved the perfusion of vancomycin through the biofilm, and decreased the penetration of rifampin but did not sterilize the membrane. These observations provide evidence that bactericidal levels of vancomycin, rifampin, or both can be attained at the surface of an infected implant. Despite this, sterilization of the biofilm was not accomplished after 72 h of treatment.

Topics: Bacterial Adhesion; Diffusion; Drug Implants; Drug Therapy, Combination; Models, Biological; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Infections of implanted devices are of increasing frequency and importance, representing a significant limitation of many therapeutic modalities. There are puzzling features of implant-associated infection including the changes in microbial flora, the tendency to chronicity and impaired responses to conservative modes of treatment. The concept of the bacterial biofilm as a shielding mechanism generated by bacteria adherent to artificial surfaces has recently been proposed as an explanation for these features. The biofilm is a term applied to a complex comprising the implant surface, adherent bacteria and a specialized matrix enclosing the bacteria. The matrix of the biofilm is an electrostatically charged glue-like extracellular polymer derived by bacterial enzymes acting on tissue carbohydrates, formed by bacteria when adherent to surfaces. This matrix binds the bacteria to the surface providing a sequestration affording selective protection against harmful elements of the environment, especially mechanisms of host defenses and antimicrobial agents. These biological systems are complex to study because of the dynamic interaction of the microbial variables, host defenses, properties of synthetic materials and the biofilm matrix itself. There is a need for a laboratory model in which the variables can be controlled permitting the researcher to examine the outcomes of modifying one variable at a time in a planned and orderly manner. The practical way to attain this end is the conduct of studies in a stable reproducible animal model of localized biofilm-implant infection. Staphylococcus epidermidis is a representative of the class of microorganisms predominant in implant-associated infection. This paper describes the development of a model utilizing an implant-S. epidermidis-biofilm infection localized to the peritoneal cavity of the mouse. The natural history of the infection has been well documented and is stable in all respects for periods exceeding 3 months. This chronicity is especially advantageous in analyzing the impact of long-term therapeutic modalities and necessary periods of recovery and assessment. A representative example of an experimental use of this model to determine the relative efficacy of antibiotic therapeutic regimes is described, demonstrating its scope and efficacy.

Topics: Animals; Catheterization; Catheters, Indwelling; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred C57BL; Peritoneal Cavity; Peritoneal Dialysis, Continuous Ambulatory; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

To describe the spectrum of clinical infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in healthcare workers.. Case series.. Two Veterans Affairs hospitals in which methicillin-resistant S aureus (MRSA) is endemic.. Five employees presenting to employee health or infectious disease clinic.. All employees had had direct exposure to patients colonized with MRSA. Employee infections included cellulitis, impetigo, folliculitis, paronychia, and conjunctivitis. MRSA was isolated from all clinically infected sites and from the anterior nares of two employees. Three employees received a variety of ineffective oral antimicrobials before MRSA was recognized as the causative agent. All infections responded to appropriate therapy.. Employees of hospitals with endemic MRSA may acquire MRSA infection. Presentation in our employees was that of relatively uncomplicated soft tissue infection, but several employees received inappropriate therapy before bacteriologic diagnosis. We recommend that culture and susceptibility testing be obtained prior to institution of therapy when hospital employees present with soft tissue infection.

Topics: Adult; Female; Hospitals, Veterans; Humans; Male; Methicillin Resistance; Middle Aged; Mupirocin; Pennsylvania; Personnel, Hospital; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Acute Disease; Child; Cholecystectomy; Cholecystitis; Combined Modality Therapy; Endocarditis, Bacterial; Floxacillin; Gallbladder; Gentamicins; Humans; Male; Ornidazole; Parenteral Nutrition, Total; Rifampin; Staphylococcal Infections; Ultrasonography

Two patients with infectious endocarditis (IE) by Staphylococcus aureus resistant to methicillin, aminoglucosides and rifampicin (SARMAR) acquired in hospital during the course of an epidemic outbreak of this microorganism in the Hospital Clínic i Provincial of Barcelona. Both patients had undergone surgery of the lower limbs. The entrance of the microorganism was the infection of the surgical wound, with bacteriemia, followed by mitral IE after a short time interval (20 days). Despite adequate treatment with vancomycin both patients died. The culture of mitral vegetation was positive for SARMAR in one. Analysis of the chromosomic DNA of all the isolations from the patients was identical and coincided with that of the SARMAR strains isolated in the epidemic outbreak of the hospital. The current situation of IE by SARMAR is reviewed and the therapeutic implications commented upon suggesting that treatment of this entity should simultaneously include the administration of vancomycin and phosphomycin or cotrimoxazole, with surgery being considered if infection persists.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; DNA, Bacterial; Drug Resistance, Microbial; Endocarditis, Bacterial; Fatal Outcome; Female; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Mitral Valve; R Factors; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Staphylococcus aureus infections have been successfully treated in animal models with the combination of fleroxacin and rifampin. We studied the influence of rifampin, a potent cytochrome P-450 inducer, on the pharmacokinetics and biotransformation of fleroxacin in 14 healthy young male volunteers. Subjects were given 400 mg of fleroxacin orally once a day for 3 days to reach steady state. After a wash-out period of 2 days, the same subjects received 600 mg of rifampin orally once daily for 7 days. On days 5 to 7 of rifampin treatment, 400 mg of fleroxacin was again administered once daily. Concentrations of fleroxacin as well as its two major urinary metabolites, N-demethyl- and N-oxide-fleroxacin, in plasma and urine were determined by reverse-phase high-performance liquid chromatography. The extent of hepatic enzyme induction by rifampin was confirmed by a significant increase of 6-beta-hydroxycortisol urinary output from 160.8 +/- 41.4 to 544.8 +/- 120.7 micrograms/4 h. There were no significant changes in the peak fleroxacin concentration in plasma (6.3 +/- 1.2 versus 6.2 +/- 1.9 mg/liter), time to maximum concentration of fleroxacin in plasma (1.1 +/- 0.9 versus 1.3 +/- 1.1 h), or renal clearance (58.3 +/- 16.4 versus 61.9 +/- 19.2 ml/min). The area under the curve AUC (71.4 +/- 15.8 versus 62.2 +/- 13.7 mg.h/liter) and the terminal half-life of fleroxacin (11.4 +/- 2.2 versus 9.2 +/- 1.1 h) decreased (P < 0.05), while the total plasma clearance increased from 97.7 +/- 21.6 to 112.3 +/- 25.8 ml/min (P < 0.01). Despite being statistically significant, this 15% increase in total plasma clearance does not appear to be clinically relevant. Metabolic clearance by N demethylation was increased ( 6.9 +/- 2.4 versus 12.5 +/- 3.2 ml/min; P < 0.01), whereas clearance by N oxidation did not change (5.8 +/- 1.1 versus 5.8 +/- 1.5 ml/min). Fleroxacin elimination was slightly increased (about 15%) through induction of metabolic clearance to N-demethyl-fleroxacin. Since fleroxacin levels remained above the MIC for 90% of the tested isolates of methicillin-susceptible S. aureus for at least 24 h, dose adjustment does not appear necessary, at least for short-term treatments.

Topics: Adult; Anti-Bacterial Agents; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme Induction; Fleroxacin; Humans; Hydrocortisone; Liver; Male; Rifampin; Staphylococcal Infections

Topics: Blood Vessel Prosthesis; Humans; Polyethylene Terephthalates; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections

Topics: Blood Vessel Prosthesis; Humans; Polyethylene Terephthalates; Polytetrafluoroethylene; Prosthesis-Related Infections; Reoperation; Rifampin; Staphylococcal Infections

Ten neonates with persistent staphylococcal bacteremia (positive blood cultures for > or = 5 days despite appropriate antibiotic therapy) received intravenous (i.v.) rifampin in combination with vancomycin with or without aminoglycoside. Their mean birth weight and length of gestation were 900 g and 27 weeks, respectively. Their ages at the time of infection ranged from 6 to 64 days (mean, 26 days). The staphylococcal isolates were methicillin-resistant Staphylococcus aureus (five isolates), methicillin-susceptible S. aureus (two isolates), and coagulase-negative staphylococci (three isolates). The mean number of bacteremia days prior to administration of i.v. rifampin was 8.3 (range, 5 to 15 days), despite a mean peak vancomycin concentration of 33 micrograms/ml. The dosing of rifampin varied from 2.5 to 10 mg/kg of body weight every 12 h. The mean duration of the rifampin course was 9.7 days (range, 3 to 16 days). Of the 10 neonates, 8 (80%) had sterile blood cultures within 24 h, 1 (10%) had a sterile blood culture within 48 h, and 1 (10%) had a sterile blood culture within 5 days of being placed on i.v. rifampin. No adverse effects were noted in this small group of infants. Seven of the 10 neonates survived; three died from unrelated complications. The MIC ranges of amikacin, vancomycin, and rifampin for the isolates were 2.0 to 16, 0.5 to 2.0, and 0.0013 to 0.04 micrograms/ml, respectively. We also studied eight infants, with a mean age of 23 days, who were receiving i.v. or oral rifampin at a dose of 10 mg/kg/day. For i.v. administration, the peak serum concentration of rifampin (mean +/- standard deviation) was 4.02 +/- 1.22 microgram/ml. The mean trough level at 12 h postifution was 1.11 +/- 0.48 micrograms/ml. For oral administration, the concentrations of rifampin in serum ranged from 0.59 to 2.86 micrograms/ml (mean, 1.86 +/- 0.96 microgram/ml) at 2 h postingestion, increasing to a peak concentration of 2.8 micrograms/ml at 8 h postingestion. The mean 12-h postingestion level was 0.77 +/- 0.03 microgram/ml. From the study of this limited series of neonates, rifampin appears to be a safe and effective addition to therapy when staphylococcal bacteremia is persistent despite vancomycin treatment.

Topics: Amikacin; Bacteremia; Chromatography, High Pressure Liquid; Drug Synergism; Drug Therapy, Combination; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

Staphylococci are the leading pathogens in continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Vancomycin appears to be an outstanding antistaphylococcal drug because resistance to it is nearly absent. The pharmacokinetics of vancomycin and clinical cure rates of peritonitis with different dosing guidelines have been studied extensively. Different dosing guidelines with IP or IV loading doses followed or not followed by IP maintenance doses are used successfully, despite the fact that some of the dosing schemes produce apparently suboptimal drug levels referring to in vitro data like the MIC value (minimum inhibitory concentration). Alternatively, aminoglycosides, cephalosporins, isoxazolyl penicillins, and broad-spectrum penicillins combined with beta-lactamase inhibitors may be used for the treatment of gram-positive peritonitis. For the above penicillins pharmacokinetic data are scarce, and clinical experience is limited. Rifampin has excellent intracellular antistaphylococcal activity and should be used in combination with other antibiotics. Although pharmacokinetic data are lacking, rifampin dosages do not require adaptation to renal function or replacement therapy.

Topics: Anti-Bacterial Agents; Humans; Penicillins; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

Ventricular obstruction and hydrocephalus are recognized complications of neurosurgical procedures and meningitis that has been previously treated. The confinement of bacterial meningitis solely to a lateral ventricle in an otherwise healthy individual, however, is rare. I describe a case in which a ventricular abscess occurred as the presenting manifestation of staphylococcal meningitis in a man who had no history of head trauma or neurosurgery.

Topics: Adult; Brain Abscess; Cerebral Ventricles; Humans; Magnetic Resonance Imaging; Male; Meningitis, Bacterial; Nafcillin; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed; Vancomycin

Based on the excellent results of experimental studies with antibiotic-bonded vascular prostheses for prevention of graft infection, gelatin-sealed grafts soaked with rifampin were implanted in situ in five patients with vascular infection. All patients were at risk for limb loss or death and could not be treated by standard techniques such as graft excision and extra-anatomic bypass. In one patient an infected aortic stump aneurysm with involvement of both renal and visceral arteries was found. He was treated by implantation of a bifurcation rifampin-soaked graft between the subdiaphragmal aorta and both renal arteries and reimplantation of celiac and superior mesenteric artery into the graft. In four patients with in-flow or runoff problems on angiography, an antibiotic-soaked graft was used for replacement of a partially or totally infected graft. Cultures were positive for Staphylococcus aureus in three and coagulase-negative staphylococci in two patients. Wound healing was uncomplicated; there was no need for amputation. After a follow-up of at least 6 months, all grafts were patent without any evidence of reinfection on computed tomographic scan. We conclude that infected vascular prostheses can be replaced in situ by rifampin-soaked grafts in patients at high risk for death or major amputation.

Topics: Aged; Blood Vessel Prosthesis; Female; Follow-Up Studies; Gelatin; Humans; Male; Middle Aged; Polyethylene Terephthalates; Prosthesis Design; Prosthesis-Related Infections; Recurrence; Reoperation; Rifampin; Staphylococcal Infections; Tomography, X-Ray Computed

Two combinations of antibiotics, clindamycin with rifampicin and cloxacillin with netilmicin, were investigated for their activity against two strains of Staphylococcus aureus (a sensitive reference strain and a methicillin-resistant clinical isolate) by means of the in vitro checkerboard technique and an in vivo infected mouse model. The mouse model allowed drug interactions to be evaluated both from the changes in the number of bacteria surviving treatment and from the measured exposure to antibiotics at the site of infection. Specimens from the latter were evaluated twice (day 0 and day 2) in each experiment. The combination of cloxacillin and netilmicin exhibited a synergistic effect against the reference strain both in vitro and in vivo, whereas synergism was obtained under in vitro conditions only against the methicillin-resistant strain. The clindamycin and rifampicin combination acted synergistically or indifferently against both strains in vitro and at day 0 of the in vivo experiments. In contrast, on day 2 of infection, this combination had significantly greater bactericidal effect (synergism) compared to the combination of cloxacillin and netilmicin. These results illustrate the difficulties of interpreting in vitro results for clinical use.

Topics: Animals; Clindamycin; Cloxacillin; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Female; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Netilmicin; Rifampin; Staphylococcal Infections; Staphylococcus aureus

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Topics: Animals; Azithromycin; Bone and Bones; Clindamycin; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Male; Osteomyelitis; Rats; Rifampin; Staphylococcal Infections

We have developed an infection resistant vascular prosthesis by bonding rifampin to Dacron grafts with the use of a collagen matrix release system. The purpose of this study was to determine the efficacy of this antibiotic-bonded graft in resisting infection after an in situ reconstruction of a previously infected prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3 cm untreated Dacron graft into the infrarenal aorta. This initial graft was deliberately infected, at the time of operation, with 10(2) organisms of Staphylococcus aureus by direct inoculation. One week later, the dogs were reexplored, the retroperitoneum debrided, and the animals randomized to undergo an end-to-end in situ graft replacement with either one of two types of prosthetic grafts: group I (collagen, n = 36) received control collagen-impregnated knitted Dacron grafts; group II (rifampin, n = 47) received experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was then subdivided to receive one of four treatment protocols: (a) no antibiotic therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000 ml) during operation and two doses of cephalosporin (cefazolin, 500 mg intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1 week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d) treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4 weeks after implantation. There were no anastomotic disruptions and all grafts were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Collagen; Dogs; Polyethylene Terephthalates; Prosthesis-Related Infections; Random Allocation; Rifampin; Staphylococcal Infections

To evaluate the effect of antimicrobial therapy on patients and staff colonized with methicillin-resistant Staphylococcus aureus (MRSA) in a skilled nursing facility and to assess the role of the environment as a potential reservoir for MRSA in the nursing home setting.. As part of a comprehensive program to control an MRSA outbreak in a nursing home, patients and staff colonized with MRSA received 1 of 3 antimicrobial decolonization regimens depending upon the site and extent of colonization. Followup cultures were performed during therapy and on days 2, 7, 14, and 30 following the completion of therapy. Cultures of the patients' inanimate environment (pajamas, sheet, and floor) were obtained during and after therapy. Antimicrobial susceptibility tests were performed on 54 MRSA isolates obtained before and 44 MRSA isolates recovered after therapy.. A 120-bed Veterans Affairs nursing home care unit.. Thirty-six patients and 7 staff nurses colonized with MRSA at 1 or more sites.. Decolonization therapy with rifampin, trimethoprim-sulfamethoxazole, and clindamycin used alone or in various combinations for 5 or 10 days in conjunction with other infection control measures employed to combat the MRSA outbreak.. Twenty (56%) of the 36 NHCU patients were either persistently colonized or became recolonized with MRSA during the 30-day followup period. Positive cultures on day 3 during therapy frequently identified patients who subsequently exhibited persistent or recurrent colonization. Before therapy, 92% of MRSA isolates were susceptible to rifampin, whereas only 43% of the isolates obtained after therapy were susceptible. Sixteen (80%) of 20 patients with persistent or recurrent colonization had rifampin-resistant strains of MRSA isolated after therapy. Twenty-three (18%) of 125 environmental cultures obtained during and after therapy from patients who exhibited persistent or recurrent colonization were positive for MRSA, in contrast to 9 (8%) of 107 from patients who were successfully decolonized.. The decolonization component of the outbreak control program was judged to be ineffective and potentially hazardous because colonization persisted or recurred in more than half of the patients, and substantial antimicrobial resistance was noted in MRSA stains isolated after therapy. Resistance, especially to rifampin, and possibly re-acquisition of MRSA from other human or environmental sources were 2 factors that appeared to impede the decolonization effort.

Topics: Aged; Aged, 80 and over; Clindamycin; Colony Count, Microbial; Disease Reservoirs; Humans; Infection Control; Male; Methicillin Resistance; Middle Aged; Nursing Staff; Oregon; Recurrence; Rifampin; Skilled Nursing Facilities; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Department of Veterans Affairs

Topics: Adult; Anaphylaxis; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Male; Peritonitis; Rifampin; Staphylococcal Infections

Topics: Administration, Oral; Adolescent; Adult; Aged; Ciprofloxacin; Drug Therapy, Combination; Humans; Methicillin Resistance; Middle Aged; Prospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Infection due to Staphylococcus aureus continues to be a source of significant morbidity and mortality. However, its treatment is increasingly complicated by the rising prevalence of resistance to antibiotics. Apart from the two recognized modes of staphylococcal resistance, namely, penicillinase production and intrinsic resistance, Sabath and associates have described a third type in which resistance is manifested by susceptibility to growth inhibition but tolerance to the lethal action of bactericidal agents. The mechanism of tolerance is attributed to a deficiency of autolytic enzyme activity in the part of bacteria, possibly secondary to an inhibition of autolysins in the tolerant staphylococcal strains. These strains are found in patients with infections responding poorly to treatment with cell-wall active antibiotics including vancomycin. Because of its unique mechanism of action and pharmacokinetic properties, rifampin has been reported to be the most active among 65 antistaphylococcal agents tested and have the capacity to kill intraleukocytic staphylococci. We present 2 cases who were cured following the addition of rifampin to previously established regimens. Case 1 was a 40-year-old male who had fever, cough, dyspnea, a right elbow abscess and left leg swelling for 2 weeks prior to admission. Culture of purulent material from the elbow abscess grew staphylococcus aureus. Chest X-ray showed bilateral septic embolism and phleborheography showed partial deep vein occlusion of the left ileofemoral vein. Case 2 was 22-year-old female with fever, chills and cough for 3 weeks. Blood culture grew staphylococcus aureus, and Chest X-ray revealed bilateral septic embolism with pneumonia. Neither of them responded to standard antibiotics which were judged adequate by in vitro sensitivity tests. Clinical cure was later obtained after rifampin was added to the regimens. These results suggest that rifampin may be a useful adjunct in the therapy of staphylococcal infections.

Topics: Adult; Drug Resistance, Microbial; Female; Humans; Male; Rifampin; Staphylococcal Infections; Staphylococcus aureus

A rabbit perforated-capsule model was utilized to study antimicrobial efficacy in treating 2-week-old Staphylococcus aureus abscesses. Animals received either ciprofloxacin (30 mg/kg), cefazolin (100 mg/kg), or ciprofloxacin (30 mg/kg) plus rifampin (20 mg/kg) every 8 h for 8 days or no antibiotic. Antibiotic levels within the abscess exceeded the MIC for the test organism. At the end of treatment, ciprofloxacin was no more effective than the control, animals receiving cefazolin had a mean log10 fall of 2.41 CFU/ml, and animals receiving ciprofloxacin plus rifampin had a mean log10 reduction of 5.06 CFU/ml (P = less than 0.01). Six days after completion of therapy, all abscesses in animals receiving ciprofloxacin plus rifampin were culture negative. Surviving organisms in animals receiving ciprofloxacin or rifampin did not develop resistance to the treatment antibiotics. In vitro time-kill curves performed with logarithmic- and stationary-phase organisms in broth, serum, and abscess fluid supernatants did not correlate with the in vivo results. Neutrophil killing studies of S. aureus pretreated with antibiotics revealed greater killing of organisms pretreated with ciprofloxacin plus rifampin than of those pretreated with cefazolin or ciprofloxacin alone. In conclusion, ciprofloxacin plus rifampin was effective therapy in this staphylococcal abscess model, compared with the moderate efficacy of cefazolin and no effect observed with ciprofloxacin alone. Enhanced neutrophil killing of S. aureus pretreated with antibiotics may be an important mechanism by which bacteria are killed in suppurative infections.

Topics: Abscess; Animals; Cefazolin; Ciprofloxacin; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Neutrophils; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus

We compared the efficacy of a long-duration (3-week) therapy of vancomycin, fleroxacin, fleroxacin plus rifampin, and vancomycin plus fleroxacin and rifampin in a recently developed rat model of chronic staphylococcal foreign-body infection. Subcutaneous tissue cages containing polymethylmethacrylate coverslips were infected with 1 x 10(5) to 5 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. Three weeks later, a quantitative culturing of the fluid that had accumulated in the cages was done (mean, 6.72 log10 CFU/ml; n = 110) and treatment was initiated after randomization. The CFUs in the cage fluid were counted on days 11 and 22 and 1 week after the termination of treatment; in addition, a final culture of coverslips (surface-bound microorganisms) was performed. The three-drug therapy was significantly superior to the other treatments on day 11 (a 5.16 log10 decrease of bacterial counts versus a 2.12 log10 to 2.94 log10 decrease for vancomycin, fleroxacin, and fleroxacin plus rifampin; P less than 0.01). On day 22, count decreases were 4.16 log10 for vancomycin, 4.91 log10 for fleroxacin (vancomycin versus fleroxacin, not significant), 6.14 log10 for two-drug therapy, and 6.34 log10 for three-drug therapy (vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin, not significant; fleroxacin-rifampin versus monotherapies, P less than 0.01); the numbers of CFU in most cage fluids were under the detection limit (20 CFU/ml) in combination groups. One week after the end of treatment, 92% of fluids and coverslips (detection limit, 1 CFU) were culture negative with tritherapy, 88% of fluids and 41% of coverslips were negative with bitherapy, and less than 12% of fluids and coverslips were negative with single drugs (for coverslips, P was <0.01 for vancomycin-fleroxacin-rifampin versus fleroxacin-rifampin and P was <0.001 for fleroxacin-rifampin versus the monotherapies). No mutants resistant to rifampin or fleroxacin were detected. In conclusion, antimicrobial combinations were highly effective and superior to single drugs in treating a chronic staphylococcal foreign-body infection for 3 weeks. The three-drug therapy decreased bacterial counts more rapidly than the two-drug therapy under study and appeared to be curative in most cases.

Topics: Animals; Cells, Cultured; Chronic Disease; Drug Interactions; Drug Therapy, Combination; Fleroxacin; Foreign-Body Reaction; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Type 1 collagen, minimally cross-linked, was used to bind one of three antibiotics (amikacin, chloramphenicol, or rifampin) to double-velour Dacron grafts to develop a prosthesis resistant to infection. Six millimeter disks of graft were placed in separate flasks (specific for each antibiotic) containing albumin in saline and continuously agitated. At daily intervals the solution was changed, and paired graft samples were removed and placed on a blood agar plate confluently streaked with bacteria. The initial zone of inhibition (centimeters squared), the time to 50% reduction of initial inhibition zone, and the overall duration of antibacterial activity were recorded on an exponential model. Grafts bonded with amikacin and chloramphenicol had an overall duration of activity of only 2 and 1 day, respectively, against Staphylococcus aureus. The collagen bonded rifampin grafts had an initial zone of 14.76 cm,2 took 3.92 days to reach 50% of initial inhibition, and had an overall duration of activity of 22.4 days. This was significantly better than grafts preclotted with 1.0 ml of rifampin (60 mg/ml) and 9 ml of blood (10.92 cm,2 1.06 days, and 5.6 days). When tested against a slime-producing Staphylococcus epidermidis (American Type Culture Collection No. 35983), the graft bonded with rifampin had inhibitory activity of up to 27.77 days with a 50% of activity eluted at 4.78 days, significantly better than the preclotted rifampin graft without collagen bonding. These data suggest that rifampin bonded by collagen can protect a vascular graft against infection from S. aureus and S. epidermidis for up to 3 weeks after implantation.

Topics: Amikacin; Anti-Bacterial Agents; Blood Vessel Prosthesis; Chloramphenicol; Collagen; Humans; In Vitro Techniques; Polyethylene Terephthalates; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Wound Infection; Time Factors

A gelatin-sealed knitted Dacron vascular graft was prepared by passive impregnation with rifampicin and implanted in the common carotid artery of 10 merino sheep. Another 10 merino sheep had an untreated graft inserted. The graft was topically inoculated with 1 mL of 10(8) colony forming units per mL of Staphylococcus aureus before wound closure. The grafts were harvested at 3 weeks and cultured. All untreated grafts and surrounding tissues became infected. One of the 10 grafts treated with rifampicin became infected (P = 0.0002) and 4 sheep with rifampicin-treated grafts had surrounding tissue infection. No bacteria cultured from the rifampicin-treated sheep developed resistance to rifampicin.

Topics: Animals; Bacterial Infections; Blood Vessel Prosthesis; Gelatin; Polyethylene Terephthalates; Rifampin; Sheep; Staphylococcal Infections; Staphylococcus aureus

The objective of this study was to test the efficacy of bonding rifampin to double-velour Dacron grafts with collagen to prevent graft sepsis. Fifty 6.0 mm Dacron grafts (length 5.0 cm) impregnated with either collagen (control) or collagen plus rifampin (experimental) were implanted in dogs end-to-end into the infrarenal aorta. The dogs were divided into four groups (each with an experimental and control subdivision) as a function of time between grafting and bacterial challenge. At 2, 7, 10, or 12 days after graft implantation, sequential groups were challenged with 1.2 x 10(8) colony forming units of Staphylococcus aureus (clinical isolate) intravenously suspended in 250 ml normal saline. Three weeks after hematogenous seeding, the grafts were sterilely harvested. One-tailed Fisher's exact test was used to compare the patency and culture-proven infection of control and antibiotic coated grafts as a function of implantation time before bacteremic challenge. In the 2-day group, four of six control grafts were infected compared with zero of six experimental grafts (p less than 0.030). In the 7-day group, five of six control grafts were infected with S. aureus versus zero of six in the experimental group (p less than 0.008). In the 10-day group, one of six experimental grafts was infected, but the control group had only two of six graft infections. In the 12-day group two of six experimental grafts and one of five control grafts were infected. These results indicate that rifampin bonded with collagen to knitted Dacron grafts will protect the graft from bacteremic infection for 7 days after implantation in a highly challenging model.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anastomosis, Surgical; Animals; Aorta, Abdominal; Bacteremia; Blood Vessel Prosthesis; Collagen; Dogs; Polyethylene Terephthalates; Prosthesis Design; Rifampin; Staphylococcal Infections; Time Factors; Vascular Patency

This study examines the efficacy of rifampin bonding to a gelatin-sealed knitted Dacron graft to prevent perioperative bacteremic vascular graft infection. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 1 mg/ml saline solution of rifampin at 37 degrees C. Nineteen dogs had thoracoabdominal aortic bypass: seven (group I) received a rifampin treated graft; six (group II) received an untreated gelatin-coated graft; and six (group III) received an uncoated Dacron graft. Two days later bacteremic challenge was produced by rapid intravenous injection of 5 x 10(5) colony forming units of methicillin resistant Staphylococcus aureus. Grafts were harvested five days after this challenge and cut into 10 fragments, each submitted to bacterial counts. Results were expressed as CFU/cm2 of graft material. In group I, no graft was infected, whereas all grafts in groups II and III were infected (p less than 0.05). Median bacterial counts from the infected fragments (median +/- SD) were similar in groups II (2.5 x 10(5) CFU/cm2) and III (4 x 10(4) CFU/cm2). Blood cultures at time of sacrifice were negative in all dogs in group I and positive in five of six dogs in groups II and III. Cultures of liver, spleen, kidney, and lung specimens were always negative in group I and positive in 22 of 24 specimens in group II and 23 of 24 specimens in group III. Soaking a gelatin-sealed Dacron graft in rifampin solution evidently prevents early bacteremic graft infection and secondary foci of infection in this model.

Topics: Animals; Blood Vessel Prosthesis; Dogs; Gelatin; Polyethylene Terephthalates; Postoperative Complications; Rifampin; Staphylococcal Infections

Because persistence of infections associated with prosthetic material despite the use of appropriate antibiotics is a major clinical problem, the antimicrobial susceptibility of bacteria responsible for a chronic subcutaneous tissue cage infection in rat was investigated ex vivo. Three to 6 weeks after the initiation of infection, suspensions of two strains of Staphylococcus aureus recovered from the foreign body surface and surrounding fluid were exposed to either oxacillin, vancomycin, fleroxacin, gentamicin, or rifampin. The MBCs of these bacteria were markedly elevated, in most cases 128 to greater than 256 times higher than the MBC of batch culture S. aureus in either logarithmic or stationary phase. Kinetic studies showed the bacteria did not grow when incubated for 2 h in Mueller-Hinton broth, possibly reflecting dormancy. Their killing was slow and incomplete by all antibiotics at greater than 8 times their MIC. These data provide direct evidence of a decreased susceptibility of S. aureus to the killing effect of antimicrobials during chronic foreign body infections in vivo.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Diffusion Chambers, Culture; Disease Models, Animal; Drug Resistance, Microbial; Fleroxacin; Foreign Bodies; Gentamicins; Kinetics; Microbial Sensitivity Tests; Oxacillin; Penicillin Resistance; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Humans; Infection Control; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Mupirocin; Plasmids; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Adult; Ciprofloxacin; Drug Resistance, Microbial; Endocarditis, Bacterial; Humans; Male; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Series of 3-piperidinyl- and 3-piperazinylrifamycins and to a certain extent 3-hydrazonorifamycins all bearing lipophilic side chains were found to exert potent hypolipidemic activity in lowering both serum cholesterol and LDL-cholesterol in rats. Starting from 3-[N'-(2,4,6-trimethylbenzyl)-N-piperazinyl]rifamycin SV (compound 25), a series of derivatives were synthesized with the aim of dissociating the hypolipidemic from the antibacterial activity, leading to the 8-O,N-dipivaloyl derivative of 25 (compound 48), which is devoid of any antibacterial activity but shows about 50-60% reduction of LDL-cholesterol and 20-30% reduction of serum cholesterol at a dose of 10 mg/kg. Compound 48 was selected for further pharmacological evaluation.

Topics: Animals; Chemical Phenomena; Chemistry; DNA-Directed RNA Polymerases; Hypolipidemic Agents; Rats; Rats, Inbred Strains; Rifamycins; Staphylococcal Infections; Structure-Activity Relationship

Shunt infections in children have become a serious problem. In order to solve this, we have been using antibiotic therapy with Rifampicin (Rifampin) for the last 2 years; the dosage is 20 mg/kg per day 1 h before surgery and then for 48 h after the surgical procedure. We have had experience with 203 children operated on between January 1987 and December 1988. The result was a significant decrease in the number of children with shunt infections. In 1980 we reported an incidence of 10%, while by 1988 the rate had gone down to 1%.

Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Equipment Contamination; Escherichia coli Infections; Follow-Up Studies; Humans; Hydrocephalus; Infant; Infant, Newborn; Infection Control; Klebsiella Infections; Postoperative Complications; Premedication; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Ventriculoperitoneal Shunt

A novel model of experimental foreign body infection was developed in rats: four perforated Teflon tissue cages per animal were implanted subcutaneously and 3 to 4 weeks later were infected with 0.5 x 10(5) to 2 x 10(5) CFU of methicillin-resistant Staphylococcus aureus. After 2 weeks, the number of CFU in the cage fluid was determined [day 1 mean, (7.25 +/- 0.79) log10 CFU/ml], and treatment with vancomycin (50 mg/kg twice a day [BID]), fleroxacin (50 mg/kg BID), or fifampin (25 mg/kg BID), alone and in combination, was initiated for a duration of 6 days. Concentrations of antibiotics in cage fluids were in the range of those encountered in clinical conditions. Eighteen hours after the last injection (day 7), the number of CFU in the cage fluid was determined and the difference between day 1 and day 7 values was calculated. Rifampin, alone and in combination with fleroxacin or vancomycin, was the most effective regimen in reducing the bacterial counts in the tissue cage fluids [(1.87 +/- 1.44, 2.18 +/- 1.02, and 2.55 +/- 1.09 log10) CFU/ml, P less than 0.001, respectively]. After treatment, cage fluids and cages were analyzed for resistant bacteria. Resistance to rifampin occurred in 15 of 19 cages in animals treated with rifampin alone and in 4 of 25 in animals treated with rifampin plus vancomycin. We detected no development of resistance to rifampin in animals treated with rifampin plus fleroxacin or to fleroxacin in animals treated with this antimicrobial agent. In conclusion, regimens including rifampin alone or in combination with vancomycin or fleroxacin were an effective treatment of foreign body infection due to methicillin-resistant S. aureus in reducing bacteria counts, but rifampin monotherapy was compromised by significant emergence of resistance. The combined therapy of fleroxacin with rifampin prevent development of resistance to rifampin.

Topics: Animals; Anti-Bacterial Agents; Ciprofloxacin; Disease Models, Animal; Drug Therapy, Combination; Fleroxacin; Foreign-Body Reaction; Male; Methicillin Resistance; Microbial Sensitivity Tests; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The brief exposure of bacteria to high antibiotic concentrations can result in prolonged suppression of bacterial growth termed postantibiotic effect (PAE). A pathogenic Staphylococcus epidermidis strain (RP-62) was exposed to 2X and 6X minimum inhibitory concentrations (MIC) of cefazolin, vancomycin, or rifampin for 1 hr and incubated for 2 to 24 hr in inhibitory-free broth. PAE was defined as the difference in time required for a 1.0 log increase in test (T) vs control (C) cultures (PAE = T-C). PAE was observed only for rifampin: 6 hr at 2X MIC and 8 hr at 6X MIC. Bacterial adherence to Dacron grafts was calculated in PAE vs control cultures by a quantitative culture technique for graft specimens incubated 2 to 24 hr. A demonstrable PAE and its impact on adherence were found to be both antimicrobial and concentration dependent. A significant decrease in staphylococcal adherence to velour-knitted Dacron was demonstrated by rifampin at 2X MIC (P less than 0.05) and 6X MIC (P less than 0.01). This phenomena may be useful in reducing bacterial adherence and colonization of bioprosthetics in the perioperative period. Preoperative suppression of staphylococcal skin flora by high dose antimicrobials can alter the capacity of these organisms to adhere to vascular prosthetic grafts and, if incorporated into antibiotic prophylaxis regimens, may reduce graft colonization.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Blood Vessel Prosthesis; Cefazolin; Cells, Cultured; Microscopy, Electron, Scanning; Polyethylene Terephthalates; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Topics: Administration, Oral; Adult; Ciprofloxacin; Endocarditis, Bacterial; Female; Glycopeptides; Humans; Male; Rifampin; Staphylococcal Infections; Teicoplanin

Topics: Cefotiam; Cross Infection; Drug Therapy, Combination; Glycopeptides; Humans; Imipenem; Methicillin Resistance; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Disinfectants; Humans; Lactams; Macrolides; Methicillin Resistance; Postoperative Complications; Quinolones; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines; Vancomycin

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem. Colonization appears to be more common than invasive disease is. Eradication of colonization or the carrier state could limit the spread of MRSA, thus reducing the potential for mortality and morbidity in other patients. The detection of patients with MRSA infection in a rehabilitation ward led to a study of the combination of novobiocin-rifampin in vivo and in vitro. We found that 300 mg of rifampin plus 500 mg of novobiocin orally twice daily for 5 days, in 18 courses of treatment given to 12 patients, resulted in the clearing of MRSA in 79% of the evaluable courses and 81% of the evaluable sites. A second course cleared MRSA from one of the patients with a treatment failure. Side effects were not noted. All 18 pretherapy isolates were susceptible to either drug in vitro, but 1 of 2 posttherapy isolates was rifampin resistant. Timed-kill studies demonstrated that the rate of killing was the same with either drug alone or both drugs together. Pretherapy isolates from treatment successes or failure were killed at the same rate by the drug combination. However, with the rifampin-resistant isolate killing ceased after 48 h. Results of this study suggest that previously untreated patients are likely to have isolates that are susceptible to the combination of drugs and that the combination is commonly effective in eradicating MRSA carriage. Since the regimen is orally administered, and thus convenient, in conjunction with other measures it has the promise of reducing the spread of MRSA in hospitals.

Topics: Administration, Oral; Cell Survival; Drug Administration Schedule; Drug Therapy, Combination; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Novobiocin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

The efficacies of the quinolones ciprofloxacin and pefloxacin alone and in combination with rifampin were compared with those of vancomycin alone and in combination with rifampin in a rat model of chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus. Neither the quinolones nor vancomycin alone was effective in reducing titers of organisms in bone after therapy, while rifampin alone was effective. All combination regimens with rifampin were more effective than the regimen with rifampin alone was, although these differences did not achieve statistical significance. Rifampin-resistant isolates were detected rarely. Quinolone-rifampin combination regimens may offer a nonparenteral option for the treatment of chronic osteomyelitis caused by methicillin-resistant S. aureus.

Topics: Animals; Chronic Disease; Ciprofloxacin; Disease Models, Animal; Drug Therapy, Combination; Male; Methicillin; Osteomyelitis; Pefloxacin; Penicillin Resistance; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Vancomycin

We compared oral temafloxacin, a new fluoroquinolone agent, with vancomycin, each with and without rifampin, in the therapy of rats with aortic valve endocarditis caused by a clinical isolate of methicillin-resistant Staphylococcus aureus. The temafloxacin, vancomycin, and rifampin MICs and MBCs were 0.78 and 1.56, 1.56 and 3.13, and less than 0.024 and 0.78 microgram/ml, respectively. The animals were classified into the following six treatment groups: vancomycin (60 mg/kg) +/- rifampin (6 mg/kg) each intramuscularly every 12 h for 5 days; temafloxacin (100 mg/kg) orally +/- rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; rifampin (6 mg/kg) intramuscularly every 12 h for 5 days; and untreated controls. All regimens with either vancomycin or temafloxacin resulted in improved survival over controls, but only temafloxacin regimens resulted in a significant reduction in bacterial counts in vegetations. These data support further investigation of the efficacy of temafloxacin in treating serious infections caused by methicillin-resistant S. aureus.

Topics: 4-Quinolones; Administration, Oral; Animals; Anti-Infective Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Fluoroquinolones; Male; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Quinolones; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Anti-Bacterial Agents; Catheters, Indwelling; Drug Interactions; Drug Therapy, Combination; Humans; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Rifampin; Staphylococcal Infections

A combination of ciprofloxacin (intravenous then oral) and oral rifampicin was tested in 14 intravenous drug users with right-sided Staphylococcus aureus endocarditis. All 10 patients who completed therapy were cured based on resolution of symptoms and negative blood cultures at 4 weeks post therapy.

Topics: Adult; Ciprofloxacin; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography; Endocarditis, Bacterial; Female; Follow-Up Studies; Humans; Male; Pilot Projects; Rifampin; Staphylococcal Infections; Substance Abuse, Intravenous

The routine laboratory monitoring of methicillin-resistant strains of Staphylococcus aureus (MRSA) at a large teaching hospital led to the detection of a new, multiply-resistant strain of MRSA, which was resistant not only to penicillin, oxacillin, methicillin, cephamandole, erythromycin, tetracycline, kanamycin and gentamicin but also to rifampicin and sulphamethoxazole-trimethoprim. The rifampicin-methicillin resistant strain of S. aureus (RMRSA) was first detected in blood cultures of babies from the newborn nursery. A bacteriological investigation of the nursery revealed the source to be a paediatric medical officer who was colonised with the resistant strain, and who at the time was receiving rifampicin for pulmonary tuberculosis. The rifampicin resistance was presumably acquired during rifampicin therapy. The outbreak in the nursery was brought to an abrupt end by treatment of the colonised medical officer with mupirocin, applied nasally twice a day for a week, and by the introduction of standard infection-control measures. Reference laboratory assistance was needed to confirm the initial assumption that the outbreak was caused by a single strain.

Topics: Bacterial Typing Techniques; Bacteriophage Typing; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Female; Humans; Infant, Newborn; Male; Methicillin; Nurseries, Hospital; Rifampin; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The MICs and MBCs for 90% of strains tested (MIC90 and MBC90, respectively) of rifampin for 75 clinical isolates of pathogenic coagulase-negative staphylococci (PCNS) were 0.03 and 0.25 microgram/ml, respectively, while the MIC90 and MBC90 of clindamycin were both greater than 25 micrograms/ml. Although no synergy between rifampicin and clindamycin was found among the 15 strains studied by the checkerboard method, 6 of 12 selected strains showed synergy by the kill-curve method. No antagonism was observed by either method. All 30 strains rapidly developed resistance to rifampin in vitro, and this could be prevented by the simultaneous presence of 1.0 microgram of clindamycin per ml in the 24 methicillin-susceptible PCNS strains. The synergy between rifampin and clindamycin observed in vitro for some strains of PCNS, together with the prevention of emergence of resistance to rifampin by clindamycin, suggests that this antibiotic combination may be useful for the treatment of infections caused by methicillin-susceptible PCNS.

Topics: Clindamycin; Coagulase; Drug Interactions; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus

The antibacterial efficacies of 4 antibiotics with different modes of action against a penicillin-tolerant and a non-tolerant strain of Staphylococcus aureus were investigated. For the in vitro studies the minimum inhibitory concentration (MIC) and the minimum bacterial concentration (MBC) were determined and short-term growth experiments at different antibiotic concentrations were performed. For the in vivo studies, antibacterial efficacy in an experimental infection in normal and granulocytopenic mice was evaluated. For erythromycin, rifampicin and ciprofloxacin, there was no difference in the MIC and MBC values for the 2 strains. Benzylpenicillin had an MBC value for the tolerant strains which was 256 times higher than the MIC; with the non-tolerant strain there was no difference. EC50 values, calculated from the in vitro short-term growth curves, gave similar results. Only benzylpenicillin exhibited a difference in activity against the tolerant strain, as reflected by the EC50 that was 290 times the EC50 for the non-tolerant strain. Studies in normal and granulocytopenic mice gave similar results: benzylpenicillin was 268 times less active against the tolerant strain than against the non-tolerant strain. Erythromycin, rifampicin and ciprofloxacin were 2-3 times less active against the tolerant strain than against the non-tolerant strain. The presence of granulocytes is important for the antibacterial effect of all antibiotics studied, since in the absence of granulocytes higher doses of the antibiotics are needed in order to obtain the same antibacterial effect as when granulocytes are present.

Topics: Agranulocytosis; Animals; Ciprofloxacin; Drug Resistance, Microbial; Erythromycin; Mice; Penicillin G; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The therapeutic activities of ciprofloxacin (25 mg/kg every 8 h), rifampin (10 mg/kg every 24 h), ciprofloxacin plus rifampin, and vancomycin (17.5 mg/kg every 6 h) were compared by using the rabbit model of Staphylococcus aureus endocarditis. Animals infected with one of two test strains (SA1199 or SA487) were randomized into treatment groups and received 6 days of therapy. For SA1199, ciprofloxacin plus rifampin was most effective at reducing vegetation bacterial counts. For SA487, ciprofloxacin plus rifampin was as effective as vancomycin but less effective than ciprofloxacin alone. Resistance to ciprofloxacin at 5- and 10-fold the MIC emerged in the test strain in 82 and 55%, respectively, of rabbits infected with SA1199 and receiving ciprofloxacin monotherapy. The combination of ciprofloxacin and rifampin decreased these frequencies to 60% (P = 0.27) and 10% (P = 0.04). No resistance to ciprofloxacin was found in rabbits infected with SA487. We conclude that ciprofloxacin and ciprofloxacin plus rifampin are as efficacious as vancomycin in this model and that combining rifampin with ciprofloxacin may decrease the frequency at which high-level resistance to ciprofloxacin emerges. However, with respect to improved efficacy, the combination of ciprofloxacin and rifampin is unpredictable and may be detrimental.

Topics: Animals; Ciprofloxacin; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Kidney; Male; Rabbits; Rifampin; Spleen; Staphylococcal Infections

Teicoplanin, a recently introduced glycopeptide antibiotic, has been used, in combination with other antibiotics, to treat 31 episodes of septicaemia caused by Gram-positive organisms. Teicoplanin has double the activity of vancomycin against many Gram-positive bacteria, but allergic reactions and toxicity appear to be infrequent. A single daily dose is sufficient to maintain therapeutic levels, which is an advantage in conditions requiring long-term treatment. Of the 31 episodes treated, 16 were associated with infective endocarditis, 11 with Hickman catheter infection, two with bone and joint infection, and two with infection of other indwelling prosthetic devices. Staphylococcus epidermidis was isolated in 18 infections, of which seven treatment courses were unsuccessful. One death occurred from an uncontrolled infection, three deaths from underlying disease (one of which had relapsed twice), and one after withdrawal of treatment following febrile reaction. Eleven episodes were cured. Six episodes of Staphylococcus aureus septicaemia were treated, of which two failed to respond, two relapsed, one improved and one was cured. The remaining seven episodes were caused by streptococci (including Streptococcus faecalis), and in all of them cure was achieved despite the lack of consistent serum bactericidal activity in vitro.

Topics: Adolescent; Adult; Aged; Aminoglycosides; Enterococcus faecalis; Female; Glycopeptides; Half-Life; Humans; Male; Middle Aged; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcal Infections; Teicoplanin

The antistaphylococcal activity of teicoplanin, a new glycopeptide antibiotic, has been evaluated in vitro and compared with that of vancomycin, fucidin, rifampicin and gentamicin. Teicoplanin was found to be as active as vancomycin against clinical isolates of Staphylococcus aureus (both methicillin-resistant and methicillin-sensitive strains). Teicoplanin was found to be more active than vancomycin against Staphylococcus epidermidis. The minimum inhibitory concentration (MIC) of teicoplanin was 2- to 4-fold lower than that of other drugs tested. The minimum bactericidal concentration (MBC) of both teicoplanin and vancomycin either equalled or exceeded by 2-fold the respective MIC's. The rate at which staphylococci were killed showed that teicoplanin at 4 X MIC produced rapid killing in 10 h and no growth was detected after 24 h.

Topics: Fusidic Acid; Gentamicins; Glycopeptides; Humans; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin

The effect of rifampicin on Staphylococcus aureus in vitro was assessed as the difference between the logarithms of the numbers of colony forming units (CFU) with and without 3 h of exposure to the drug. The efficacy was expressed as the EC50, i.e. the concentration at which 50% of the maximal effect was obtained, calculated according to the Hill equation. The value found for the EC50 was 3.8 micrograms/l and the mean maximal effect was a log ratio of 5.03 (SEM 0.33). In vivo experiments were performed in normal mice and in mice made granulocytopenic by irradiation. The effect of rifampicin was assessed as the CFU count 5 h after the injection of a suspension of bacteria into the thigh muscle and 4 h after the administration of rifampicin. The efficacy was expressed as the ED50, i.e. the dose at which 50% of the maximal effect is obtained. This value was 0.18 mg/kg for the normal mice and 0.15 mg/kg for the granulocytopenic mice. The corresponding mean plasma concentrations of non-protein-bound drug were 28 and 24 mg/l, respectively. Thus, the EC50 was found to be much higher in vivo than that in vitro. This difference should be taken into account when parameters of in-vitro efficacy are applied to establish dosage schedules.

Topics: Agranulocytosis; Animals; Male; Mice; Rifampin; Specific Pathogen-Free Organisms; Staphylococcal Infections; Staphylococcus aureus

Retrospective review of 197 patients with methicillin-resistant Staphylococcus aureus (MRSA) identified 47 in whom a regimen for eradication of MRSA colonization could be evaluated. The patients were elderly (mean age, 67.7 years), with 53% transferred from another institution and 53% treated in an intensive care unit. A mean of 47.1 days of hospitalization with an average of 4.9 antibiotics preceded the first MRSA culture. The usual regimen (mean, 6.0 days) was oral trimethoprim-sulfamethoxazole, 160/800 mg twice daily, oral rifampin, 600 mg once daily, and bacitracin ointment three times a day. Eradication succeeded in 40 patients, 9 relapsed, and MRSA persisted in 7. Twenty-four of 25 nares sites were cleared but only 16 of 22 other sites. MRSA infection eventually developed in 36%. No adverse reactions to the eradication regimen were noted. Although this treatment for MRSA carriage was safe and effective, decreased efficacy outside the nares and relapse limited its value.

Topics: Aged; Bacitracin; Carrier State; Cross Infection; Drug Combinations; Drug Therapy, Combination; Hospital Bed Capacity, 300 to 499; Humans; Methicillin; Middle Aged; Nebraska; Penicillin Resistance; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Staphylococcus epidermidis is an infrequent cause of native valve endocarditis. We describe two cases associated with mitral valve prolapse, and discuss the significance, diagnosis and management of this condition.

Topics: Adult; Endocarditis, Bacterial; Floxacillin; Fusidic Acid; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Prolapse; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Topics: Catheters, Indwelling; Drug Therapy, Combination; Erythromycin; Floxacillin; Humans; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Retrospective Studies; Rifampin; Staphylococcal Infections

Groups of mice infected with 3.3 X 10(8) Staphylococcus aureus via the tail vein were treated three days later with rifampicin (13 mg/kg), vancomycin (33 mg/kg), or teicoplanin (33 mg/kg). Rifampicin was the most effective agent (28 out of 29 survivors). Vancomycin and teicoplanin were of equivalent efficacy (21 of 29 and 24 of 29 survivors, respectively). When intraleucocytic staphylococci were incubated with rifampicin (1 or 20 mg/l), vancomycin (100 mg/l), or teicoplanin (100 mg/l), rifampicin was the most active drug. Vancomycin and teicoplanin were similar.

Topics: Animals; Anti-Bacterial Agents; Glycopeptides; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Random Allocation; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

Topics: Factor VIII; Glycopeptides; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Teicoplanin

Teicoplanin and rifampicin were evaluated as single and combined agents in the treatment of endocarditis due to Staphylococcus epidermidis in the rabbit model. Rabbits were treated for ten days and the number of bacteria in vegetations determined. At the end of ten days the geometric mean number of bacteria in the vegetations were 5.53 X 10(8), 6.68 X 10(6). 1.10 X 10(4), 2.57 X 10(1) cfu/g of vegetation for control, teicoplanin, rifampicin, and teicoplanin plus rifampicin groups respectively. The MIC and MBC values of the S. epidermidis isolates were 0.78 mg/l for teicoplanin and less than or equal to 0.10 mg/l for rifampicin. In the rifampicin treated group three post-treatment isolates of S. epidermidis tested exhibited marked resistance to rifampicin with MIC and MBC values greater than or equal to 200 mg/l. Teicoplanin and rifampicin were both effective as single agents in the clearance of S. epidermidis from the bloodstream. Rifampicin was more effective than teicoplanin in the clearance of S. epidermidis from vegetations but teicoplanin in combination with rifampicin was more effective than either drug alone.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Glycopeptides; Male; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin

Thirty-two patients were treated by ofloxacin on bacteriological documented infections. They were Enterobacterias: n = 15 (MIC less than or equal to 0.06 to 0.5 microgram/ml); Pseudomonas aeruginosa and Acinetobacter: n = 1 (MIC 0.5 and 4 micrograms/ml); Staphylococcus: n = 6 (MIC less than or equal to 0.06 to 4 micrograms/ml); Pneumococcus: n = 1; Mycoplasma: n = 1; Chlamydia psittaci: n = 2; Legionella pneumophila: n = 1; Rickettsias: n = 4 (three mediterranean fevers one query fever). Ofloxacin was given orally from 400 to 800 mg per day (5 to 15 mg/kg/day). It was used alone 26 times and on 6 occasions it was associated with rifampin on 6 staphylococcal infections. On 19 cases it was used after failure or intolerance of initial therapy. Thirty times it was the first antibiotic substance used. Results were good mainly: 1) on nine pneumonitis (enterobacterias: 4; Pneumococcus: 1; Mycoplasma: 1; Chlamydia: 2; Legionella: 1) during a mean duration of twenty days; 2) urinary infections (n:7) provoked by E. coli and Enterobacter cloacae (mean duration: 20 days); 3) 4 osteo-articular-infections (mean duration: 77 days); 4) Rickettsial infections (n:4) during a mean duration of 11 days. Results are particularly noteworthy because patients treated had severe infections: 12 bacteremias, 1 endocarditis and 1 purulent meningitis. None severe adverse effect was observed.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Ofloxacin; Oxazines; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Urinary Tract Infections

At the Ann Arbor Veterans Administration Medical Center, 30 patients over a 6-month period became nosocomially infected or colonized by methicillin-resistant Staphylococcus aureus. Immediate institution of strict infection control measures, in conjunction with surveillance cultures of personnel and treatment of carriers, did not limit spread of the outbreak strain of MRSA. Multiple nonoutbreak strains, phenotypically exhibiting heteroresistance, were also uncovered. Thirteen hospital personnel were identified as MRSA carriers. Trimethoprim-sulfamethoxazole (TMP-SMX) and rifampin initially eradicated the carrier state, documented by anterior nares cultures in 13 courses of treatment in 11 employees. However, three employees were recolonized, one at one month, one at both one and four months, and one at four months. Treatment of the carrier state reservoir among personnel appeared to have no effect on the emergence and spread of nosocomial MRSA.

Topics: Carrier State; Cross Infection; Disease Outbreaks; Disease Reservoirs; Drug Combinations; Hospitals, General; Hospitals, Veterans; Humans; Methicillin; Michigan; Penicillin Resistance; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Changes in activity of beta-lysins in blood serum were studied in the time course on albino mice infected with staphylococci and treated with rifampicin, lincomycin and inactivated staphylococcal vaccine administered in combination or alone. It was shown that staphylococcal infection lowered activity of the serum beta-lysins in the animals and therapeutic use of inactivated staphylococcal vaccine stimulated beta-lysin activity. Therapeutic use of rifampicin or lincomycin under the same conditions lowered activity of beta-lysins. The inhibitory effect of rifampicin was less pronounced. Combined use of the antibiotics and the vaccine promoted an increase in activity of beta-lysins as compared to the use of the antibiotics alone.

Topics: Animals; Antimicrobial Cationic Peptides; Bacterial Vaccines; Blood Proteins; Drug Evaluation, Preclinical; Drug Therapy, Combination; Lincomycin; Mice; Proteins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Therapy with vancomycin alone or ciprofloxacin alone did not significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in bone in rats with experimental osteomyelitis, compared with the number in control rats. Treatment with rifampin significantly (p less than 0.01) decreased the number of MRSA per gram of bone compared with the number in control animals. There was no significant difference in the results of therapy with rifampin compared with the results obtained with the combination of vancomycin plus rifampin. The combination of ciprofloxacin plus rifampin was the most effective regimen for the treatment of MRSA experimental osteomyelitis and the results of therapy were significantly (p less than 0.01) superior to those following treatment with rifampin alone or the combination of vancomycin and rifampin. Following cessation of antimicrobial therapy, significant (p less than 0.01) regrowth of MRSA in bone occurred in animals treated with rifampin alone or ciprofloxacin plus rifampin. The emergence of resistance of MRSA during treatment occurred in two rats treated with rifampin alone and in one treated with rifampin plus vancomycin.

Topics: Animals; Anti-Bacterial Agents; Ciprofloxacin; Drug Therapy, Combination; Osteomyelitis; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections; Vancomycin

The efficacy of treating established vascular graft infections with rifampin and clindamycin (preferentially concentrated in leukocytes) and cefazolin (not concentrated in leukocytes) was studied in a canine model. Infrarenal aortic, 6 mm by 6 cm knitted Dacron double velour grafts were implanted and infected with 10(8) colony-forming units (CFU) of coagulase-positive Staphyloccus aureus organisms injected intravenously immediately after graft placement. Antibiotic therapy was instituted at 3 months postimplantation. Three groups were studied: (I) untreated controls (n = 3); (II) therapy with intravenous cefazolin 15 mg/kg/8 hr for 28 days (n = 7); and (III) combined therapy with intravenous rifampin 13 mg/kg/24 hr and intravenous clindamycin 13 mg/kg/8 hr for 28 days (n = 7). Grafts were removed for quantitative bacteriologic studies after the 28-day course of therapy. Two group I control grafts remained patent with 6.4 X 10(6) and 8.1 X 10(3) CFU S. aureus/gm of graft. The third control graft was thrombosed. Two group II animals demonstrated 1.6 X 10(7) and 2.3 X 10(5) CFU S. aureus organisms/gram of graft, respectively; the remaining five group II grafts were free of organisms. All group III grafts were sterile--a significant difference (p less than 0.05) from group I grafts. In this experimental model, established prosthetic graft infections were eradicated by intensive treatment with antibiotics preferentially concentrated in leukocytes.

Topics: Animals; Blood Vessel Prosthesis; Cefazolin; Clindamycin; Disease Models, Animal; Dogs; Drug Therapy, Combination; Female; Leukocytes; Rifampin; Staphylococcal Infections; Surgical Wound Infection

A methicillin- and rifampin-resistant strain of Staphylococcus aureus was introduced into a university hospital by interstate transfer of an infected surgical patient. An outbreak occurred, and 17 patients became infected or colonized with the epidemic strain. Reservoirs appeared to be patients who were infected or colonized with the resistant S aureus and possibly two nurses who were nasal carriers. The outbreak isolate was likely spread by contact with contaminated hands of personnel. A retrospective case-control study identified tracheostomy, débridement, and irrigation of wounds by power spray and prolonged nasogastric intubation as risk factors for acquisition of the epidemic strain. Analysis of factors by groups indicated that surgical procedures, wound care procedures and instrumentation of the respiratory tract were significantly associated with cases. The nasal carrier state was eradicated in two nurses by topical application of 5% vancomycin. The epidemic strain was eradicated from the hospital 8 months after it was introduced.

Topics: Carrier State; Cross Infection; Disease Outbreaks; Female; Hospital Bed Capacity, 500 and over; Humans; Intensive Care Units; Male; Methicillin; Middle Aged; Penicillin Resistance; Personnel, Hospital; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; Virginia

Rifampin-induced thrombocytopenia has been recognized as an immunological reaction associated with intermittent high-dose therapy, and rarely seen with daily low-dose regimens. Our patient was a 33-year-old male with Marfan's syndrome who was given rifampin 600 mg/d po along with intravenous vancomycin for the treatment of Staphylococcus epidermidis endocarditis. His platelet count dropped from a baseline of 519,000/mm3 to 4000/mm3 after four doses of rifampin. Petechiae were present on the lower extremities without the presence of other bleeding sites. Rifampin, low-dose aspirin, and dipyridamole were discontinued. His platelet count returned to normal nine days after discontinuation of therapy. With the increasing use of rifampin for the treatment of nontuberculosis infections, clinicians should recognize the possibility of this drug causing such serious immunological reactions as thrombocytopenia, hemolytic anemia, acute renal failure, and shock with daily or intermittent therapy.

Topics: Adult; Endocarditis, Bacterial; Humans; Male; Rifampin; Staphylococcal Infections; Thrombocytopenia

Topics: Anti-Bacterial Agents; Cephalosporins; Drug Therapy, Combination; Erythromycin; Humans; Methicillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Streptomycin; Vancomycin

We tested the ability of teicoplanin alone and in combination with rifampicin or gentamicin to cure experimental endocarditis and granuloma pouch infections in rats caused by Streptococcus faecalis, Str. sanguis, methicillin-sensitive and -resistant Staphylococcus aureus. Vancomycin and ampicillin were also tested. Teicoplanin was more active than vancomycin and ampicillin. Combinations of teicoplanin with rifampicin or gentamicin were significantly more effective than single drug therapy. These results suggest that teicoplanin could be an interesting alternative to vancomycin in the treatment of serious streptococcal and staphylococcal infections in man.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Glycopeptides; Granuloma; Male; Methicillin; Penicillin Resistance; Rats; Rats, Inbred F344; Rifampin; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Teicoplanin; Vancomycin

This study compared teicoplanin with vancomycin without and with gentamicin and/or rifampin for treatment of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis. In rabbits treated for three days and killed 12 hr after the last doses of antimicrobial agents, no significant difference in reducing bacterial titers of vegetations was detected between vancomycin and teicoplanin without and with gentamicin and/or rifampin. Addition of gentamicin and/or rifampin to vancomycin or teicoplanin significantly reduced bacterial titers of vegetations compared with vancomycin or teicoplanin alone. Addition of rifampin alone or gentamicin plus rifampin was significantly more effective than addition of gentamicin alone. In rabbits treated for three days and killed seven days after the last doses of antimicrobial agents, no significant difference in sterilizing vegetations was detected between vancomycin and teicoplanin with gentamicin and/or rifampin. However, there was a trend (probably due to the longer elimination half-life of teicoplanin in serum) that clearly favored teicoplanin over vancomycin. Teicoplanin plus rifampin without or with gentamicin is at least as effective as vancomycin plus rifampin without or with gentamicin for treatment of experimental endocarditis due to methicillin-resistant S. epidermidis.

Topics: Animals; Endocarditis, Bacterial; Female; Gentamicins; Glycopeptides; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Teicoplanin; Vancomycin

The risk of infection in vascular prosthetic conduits appears to be greatest in the perioperative period and the organism most frequently found is Staphylococcus aureus. Previous work suggests that antibiotics must be chemically bonded to the material to resist rapid washout caused by the flow of blood through the graft. The exception to this is rifampin, which remains fixed in Dacron prostheses after passive addition of the agent to aliquots of blood used to clot the interstices of porous Dacron grafts. This characteristic of rifampin is presumed to be caused by its poor water solubility. This potential infection resistance was challenged in a standard model of a canine infrarenal aortic graft by intravenous infusion of S. aureus organisms (10(7)) in the perioperative period. The grafts of five animals were preclotted with 9 ml of autogenous blood plus 1 ml of rifampin (60 mg/ml). A second group had similar procedures with 1 ml of cefazolin (238 mg/ml) substituted for the rifampin, and a control group had 1 ml of saline solution added to the 9 ml aliquot of blood. The animals were killed at 3 weeks and examined for clinically apparent infection. Rings of the graft material were also removed aseptically and cultured. All five grafts preclotted with cefazolin had clinical and culture evidence of infection (S. aureus), as did the grafts of three of the five control dogs. None of the grafts preclotted with rifampin was infected (p less than 0.05). Addition of rifampin to the blood used to clot the graft interstices appears to be a simple way of imparting graft resistance to perioperative sepsis.

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Dogs; Graft Occlusion, Vascular; Polyethylene Terephthalates; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Time Factors

Topics: Aortic Valve; Aortic Valve Stenosis; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Time Factors; Vancomycin

Epiglottitis (supraglottitis) in the adult, once thought a rare entity, has been reported in the literature with increasing frequency since the late 1960s. Five cases occurring in our hospital over a 12-week period prompted this report. Historical and literature reviews followed by five case reports and discussion, illustrate the important diagnostic and therapeutic features of this disease.

Topics: Adult; Airway Obstruction; Epiglottitis; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Laryngitis; Male; Middle Aged; Rifampin; Staphylococcal Infections

The authors evaluated the susceptibility of some antibiotics against several Staphylococci subdivided in lyogroups and different resistance patterns: methicillin-susceptible/penicillin-susceptible (MS/PS), methicillin-susceptible/penicillin-resistant (MS/PR), methicillin-resistant/penicillin-resistant (MR/PR) and methicillin-resistant/penicillin-susceptible (MR/PS). The antimicrobial agents used were: methicillin, penicillin, rifampin, tetracycline, lincomycin, erythromycin, gentamicin and netilmicin. Netilmicin showed better activity against all Staphylococcus strains tested, particularly against coagulase-negative.

Topics: Anti-Bacterial Agents; Erythromycin; Gentamicins; Humans; Lincomycin; Methicillin; Microbial Sensitivity Tests; Netilmicin; Penicillin Resistance; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Tetracycline

We present 6 patients in whom prosthetic failure occurred because of sepsis owing to Staphylococcus epidermidis. Such failure occurs in grafts in other areas and is caused by the high resistance of the organism to conventional antibacterial measures. Therapy with appropriate antibiotics, that is aminoglycosides, vancomycin and rifampin, and the need for an early operation are stressed.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Diabetes Complications; Drug Resistance, Microbial; Erectile Dysfunction; Humans; Male; Middle Aged; Penis; Prostheses and Implants; Prosthesis Failure; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Testis; Vancomycin

Topics: Adolescent; Adult; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Rifampin; Staphylococcal Infections; Staphylococcus

Two cases of ventriculitis with Staphylococcus epidermidis that failed on therapy with an antistaphylococcal penicillin are presented. Both infections responded to a combination of intravenous and intraventricular vancomycin and rifampin. Vancomycin and rifampin represent an important antibiotic regimen for the management of resistant infections of the central nervous system, especially with those due to S. epidermidis or methicillin-resistant Staphylococcus aureus.

Topics: Anti-Bacterial Agents; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Child; Craniocerebral Trauma; Encephalitis; Female; Humans; Infant; Injections, Intraventricular; Male; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Topics: Dermatitis; Drug Therapy, Combination; Humans; Ketoconazole; Rifampin; Staphylococcal Infections; Streptococcal Infections

A series of 4-deoxypyrido[1',2':1,2]imidazo[5,4-c]rifamycin SV derivatives (6-11) were prepared that demonstrated high antibacterial activity suitable for an intestinal disinfectant. These compounds are zwitterionic in nature and are poorly absorbed through the gastroenteric tract but maintain the ability to cross the bacterial cell wall. X-ray crystallographic data are presented to demonstrate the zwitterionic nature of these compounds. The structure-activity relationship of this novel series of antibiotics is discussed and the derivative with the highest ratio between subcutaneous and oral activity (6) was selected for clinical development. At the outset of this work several 3-(quaternary ammonium bromides) (1-5) were prepared and tested for antibacterial activity. These compounds were demonstrated to be too polar to even cross the bacterial cell wall but led to the synthesis of 6-11.

Topics: Animals; Bacterial Infections; Cell Wall; Chemical Phenomena; Chemistry; Digestive System; Intestinal Absorption; Mice; Rats; Rifamycins; Staphylococcal Infections; Structure-Activity Relationship

Seven patients with severe methicillin-resistant Staphylococcus aureus infections (5 with bacterial endocarditis, 1 with mediastinitis and 1 with meningitis and septicaemia) were treated with rifampicin combined with vancomycin in 6 cases and with gentamicin in 1 case. The 7 strains initially isolated from haemocultures were resistant to methicillin and sensitive to rifampicin. In 4 of these patients (3 of whom received vancomycin and 1 gentamicin) clinical and bacteriological failure was observed, with selection of rifampicin-resistant mutants. Bactericidal activity was always mediocre in both serum and cerebrospinal fluid, with insufficient vancomycin and gentamicin concentrations in 3 patients. An in vitro study of the combined antibiotics by the chequer-board method suggested antagonism in 3 of these 4 cases. Thus, in spite of its excellent activity and unquestionable effectiveness, rifampicin should be used with caution in severe staphylococcal infections.

Topics: Anti-Bacterial Agents; Drug Antagonism; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Rifampin; Staphylococcal Infections

Bilaterally velour, polyester vascular prostheses were soaked with antibiotics: vibramicin, gentamicin and riphamicin. To obtain more stable binding of the prostheses with the antibiotics, physico-chemical modification of its surface was made. The prostheses retained their bacteriocidal properties even after 120 hours of being in the arterial system of a dog. Experiments of animals show the prostheses are effective in fighting back experimental infection.

Topics: Animals; Anti-Bacterial Agents; Aorta, Abdominal; Blood Vessel Prosthesis; Dogs; Doxycycline; Drug Implants; Evaluation Studies as Topic; Female; Follow-Up Studies; Gentamicins; Male; Poland; Polyesters; Rifampin; Staphylococcal Infections; Surface Properties; Surgical Wound Infection; Textiles

The incidence of methicillin-resistant staphylococcal infections, for which vancomycin hydrochloride remains the only active cell-wall antibiotic therapy, is rising. Some physicians have been combining other antibiotics with vancomycin in hopes of obtaining a more effective regimen for the therapy of these infections. Rifampin has been advocated as a concurrent second antibiotic because of its extraordinary potent bactericidal activity for Staphylococcus aureus. When rifampin is used in combination with a cell-wall antibiotic, suppression of the development of rifampin resistance has been thought possible. We report a case of infection caused by a methicillin-resistant S aureus in which the rifampin resistance occurred during therapy with vancomycin and rifampin. The rifampin resistance was stable and was present after ten serial broth and agar passages. Physicians are cautioned against the indiscriminant or routine use of rifampin as a second antibiotic in combination with vancomycin for the therapy of infections caused by S aureus.

Topics: Adult; Humans; Male; Methicillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The antistaphylococcal activity of rifapentine, a new rifamycin SV derivative, was evaluated in vitro and compared with that of rifampin. A total of 313 staphylococcal strains freshly isolated from clinical material and including representatives of all currently recognized Staphylococcus species of human origin were used. The susceptibility to methicillin of all the test strains was determined preliminarily. Despite minor differences with some species, the MICs of rifapentine were found to be substantially similar to those of rifampin. Methicillin-resistant strains of all species were most resistant to rifapentine and rifampin than were their methicillin-susceptible counterparts. For most strains tested, the MBCs of both rifamycins exceeded by twofold the respective MICs. Both the checkerboard dilution and time-kill methods were used to determine the interactions of rifapentine or rifampin with six different antibiotics: cefamandole, vancomycin, teicoplanin, gentamicin, erythromycin, and fusidic acid. No significant differences between the two rifamycins in the combinations were observed against either methicillin-susceptible or methicillin-resistant strains. Minor differences were noted depending on the second antibiotic tested or the staphylococcal species examined. Antagonism was never observed, and indifference was the prevalent response. Cases of synergism were observed occasionally with the checkerboard method and slightly more often with the time-kill method.

Topics: Anti-Bacterial Agents; Drug Combinations; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus; Time Factors

Topics: Cross Infection; Disease Outbreaks; Drug Interactions; Hand Disinfection; Humans; Methicillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; United States; Vancomycin

The pharmacokinetics and bacteriological efficacy of nafcillin (NFPC), vancomycin (VCM), amikacin (AMK) and rifampicin (RFP) alone and in VCM combinations were evaluated in the experimental rabbit meningitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA). The mean concentrations of NFPC, VCM, AMK and RFP in cerebrospinal fluid (CSF) with MSSA meningitis exceeded the minimal bactericidal concentrations of MSSA during 8 hours therapy period. The mean CSF penetration rates of the 4 drugs during therapy were from 1% to 26% which are comparable to those observed in humans with meningitis. The median CSF bactericidal titers of RFP, VCM plus RFP, AMK, VCM plus AMK regimens were larger than 1:8 during therapy of MSSA meningitis study. In experimental MRSA meningitis, RFP and VCM plus RFP achieved titers greater than 1: 16 during therapy and at 24 hours. No statistically significant reduction in the CSF bacterial colony count was obtained with any of the antibiotic regimens in MSSA meningitis. By contrast, in 8 hours MRSA meningitis model, significant reductions in the number of MRSA were observed in animals treated for 8 hours with VCM plus RFP (P less than 0.01), RFP (P less than 0.05), and NFPC plus RFP (P less than 0.01).

Topics: Amikacin; Animals; Child; Drug Therapy, Combination; Humans; Kanamycin; Kinetics; Meningitis; Methicillin; Nafcillin; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Two patients with prosthetic valve endocarditis due to methicillin-resistant Gram-positive cocci (Staphylococcus epidermidis and Micrococcus spp.) are described. They were successfully treated with rifampicin combined first with an aminoglycoside and later with co-trimoxazole or co-trimoxazole plus vancomycin. The addition of rifampicin to these antibiotics resulted in enhanced serum bactericidal activity. High doses of rifampicin (1200-1800 mg) for 7-8 weeks did not cause any serious side-effect. Surgery was not required. During surveillance for more than 2 years endocarditis did not recur.

Topics: Adult; Aminoglycosides; Drug Combinations; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Methicillin; Microbial Sensitivity Tests; Micrococcus; Middle Aged; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Studies of in vitro and in vivo bactericidal interactions of vancomycin plus rifampin against Staphylococcus aureus have yielded conflicting results. In this study the efficacy of this drug combination in experimental endocarditis due to a methicillin-resistant strain of S. aureus was investigated. Left-sided endocarditis was induced in 84 rabbits by an infecting strain that had been found to be synergistically killed by vancomycin plus rifampin in vitro when tested by the timed-kill curve technique; in contrast, the checkerboard technique had indicated that the two drugs were antagonistic against this strain. Infected animals received no therapy, vancomycin alone (30 mg/kg per day), rifampin alone (20 mg/kg per day), or both drugs (in the same doses). The combination was significantly more effective than the single-drug regimens in terms of (1) reduction of mean methicillin-resistant S. aureus vegetation titers (P less than .05-.0005), (2) rate and incidence of sterilization of vegetations (P less than .0005), and (3) rate of "radical" cure of endocarditis (P less than .005). Vancomycin alone and vancomycin plus rifampin were equally effective in reducing mortality and sterilizing renal abscesses. The use of vancomycin prevented the in vivo development of resistance to rifampin. No evidence that rifampin exerted an antagonistic effect on the in vivo bactericidal activity of vancomycin was found.

Topics: Animals; Creatinine; Disease Models, Animal; Drug Therapy, Combination; Endocarditis, Bacterial; Kidney; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Development of rifampin-resistant Staphylococcus epidermidis was documented in three patients receiving vancomycin and rifampin therapy for prosthetic valve endocarditis. The minimum inhibitory concentrations and minimum bactericidal concentrations of rifampin for the original three isolates were 0.4 micrograms/mL or less. Organisms cultured during relapse or prosthetic valve replacement had minimum inhibitory concentrations of rifampin that were 12.5, 50, and greater than 100 micrograms/mL, respectively. Surgical intervention was necessary in all patients. One died, and one required a second prosthetic valve placement. The patients were treated with vancomycin plus aminoglycoside following identification of rifampin resistance. These observations suggest that vancomycin and rifampin may not be adequate therapy for prosthetic valve endocarditis caused by S epidermidis.

Topics: Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Reoperation; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tobramycin; Vancomycin

We report the cases of 2 female patients aged 69 and 61 yr, suffering from fulminant hepatitis induced by pirprofen, a new nonsteroidal antiinflammatory drug. The duration of pirprofen administration before the onset of hepatitis was long, 7 and 9 mo, respectively. Hepatitis was not preceded or accompanied by hypersensitivity manifestations. The liver lesion consisted of massive, predominantly centrilobular hepatic cell necrosis and microvesicular steatosis. One patient died of liver failure. Although the risk of fulminant hepatitis is very low, we recommend that, in patients taking pirprofen for more than 2 mo and complaining of asthenia, nausea, or vomiting, serum aminotransferase levels should be measured and administration of the drug should be interrupted as soon as an increased level is noted.

Topics: Aged; Alanine Transaminase; Amikacin; Chemical and Drug Induced Liver Injury; Female; Humans; Middle Aged; Phenylpropionates; Rifampin; Spondylitis, Ankylosing; Staphylococcal Infections; Vancomycin

A retrospective analysis of 10 adult patients with community-acquired Staphylococcus aureus meningitis was performed in order to elucidate the characteristics and treatment of this lethal disease. In all patients, a focus of infection outside the central nervous system was apparent at presentation. A poor prognosis was associated with severe underlying disease, greater degree of hyponatremia at presentation, development of seizures, failure of nuchal rigidity to develop, persistent or recurrent bacteremia, and the presence of concurrent S. aureus bronchopneumonia. Degree of deterioration in mental status and cerebrospinal fluid pleocytosis, protein levels, and glucose levels did not appear to have any prognostic significance. Therapy with rifampin and a semisynthetic penicillin effected a cure in all six patients treated with this regimen. In contrast, three of four patients treated with other antibiotic combinations died. On the basis of this experience, it is concluded that further trials with rifampin in combination with another anti-staphylococcal antibiotic for the treatment of S. aureus meningitis are warranted.

Topics: Adult; Aged; Blood Glucose; Cerebrospinal Fluid Proteins; Female; Glucose; Humans; Hyponatremia; Leukocyte Count; Male; Meningitis; Middle Aged; Nafcillin; Oxacillin; Prognosis; Retrospective Studies; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Three children had staphylococcal infections of the CNS. In two cases the organisms were resistant to methicillin sodium. Each case was treated with a combination of vancomycin hydrochloride and rifampin; in one instance vancomycin alone had been unsuccessful. The addition of rifampin resulted in prompt clinical and bacteriologic resolution. Satisfactory levels of rifampin were achieved by administering the drug either orally or intravenously, and in one patient oral administration of rifampin produced assayed levels in subdural pus many times that required for minimal bactericidal activity. Combination therapy with vancomycin and rifampin is recommended for staphylococcal infections of the CNS.

Topics: Adolescent; Brain Diseases; Cellulitis; Central Nervous System Diseases; Drug Therapy, Combination; Empyema, Subdural; Female; Humans; Infant; Male; Meningitis; Orbital Diseases; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Cyclosporins; Drug Interactions; Drug Therapy, Combination; Female; Humans; Middle Aged; Rifampin; Skin Diseases; Staphylococcal Infections

Topics: Adult; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Oxacillin; Rifampin; Staphylococcal Infections

Topics: Chlamydia Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Haemophilus Infections; Humans; Meningitis, Meningococcal; Rifampin; Staphylococcal Infections; Trimethoprim

Analysis of 20 cases of staphylococcal septicemia, observed over 1 1/2 months in a general hospital, confirms that these infections are frequent and severe. They occurred in compromised hosts and were nosocomial infections in 2/3 of cases. An intravenous device (particularly a central venous catheter) was associated with 70% of staphylococcal septicemia. Study of bacterial susceptibility to antibiotics and clinical course leads to advocate that high risk patients with fever be initially given rifampin combined with netilmicin.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Rifampin; Sepsis; Staphylococcal Infections

Selection of rifampicin-resistant Staphylococcus aureus has been described in vitro and in vivo when this compound is given as monotherapy or orally. That this occurrence may be prevented by combination antibiotic therapy is generally accepted. We report 25 cases of severe staphylococcal infection treated by a synergistic association of rifampicin with an aminoglycoside, vancomycin, or a macrolide. Therapy failed as a result of selection of the same rifampicin-resistant Staphylococcus aureus (serotype and lysotype) in seven cases. This finding may be explained by insufficient diffusion or inactivation of the other antibiotic in the infection site.

Topics: Adolescent; Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus

During an outbreak, 25 severely impaired patients (mean age 62) presented with severe infections due to Staphylococcus aureus resistant to oxacillin and aminoglycosides. All strains were isolated in pure culture and diagnostic procedures included transtracheal puncture and bone biopsy. Median MICs were: oxacillin 50 mg/l, gentamicin 12.5 mg/l, tetracycline 25 gm/l, vancomycin 0.195 mg/l, rifampicin 0.097 mg/l and minocycline 0.195 mg/l. All patients were treated with rifampicin (600 mg/day) and minocycline (200 mg or 400 mg/day) administered together intravenously or orally bid. Mean duration of treatment was 22 days (range 5 to 119). Overall results were 19/25 infections cured and one improved. Five were failures due mostly to emergence of Staph. aureus resistant to rifampicin. No side effects were noted. These preliminary results suggest that rifampicin plus minocycline may be useful in the treatment of severe infections due to multi-resistant Staph. aureus.

Topics: Adolescent; Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Rifampin; Staphylococcal Infections; Tetracyclines; Urinary Tract Infections

Rifampicin is a suitable drug for treating staphylococcal bone and articular infections, because high levels are obtained in the human tissues. The best oral dose is 600 mg 12 hourly. The serum levels range from 10 to 15 mg/l at the peak concentration and from 0.2 to 0.6 mg/l 8 h after oral administration of 600 mg. The ratio for cancellous bone/serum is 0.41 at 3 h and 0.39 at 12 h, and for cortical bone/serum is 0.20 at 3 h after a dose of 600 mg. In every case, tissue levels paralleled serum levels; cancellous bone levels are greater than the MIC of Staphylococcus aureus strains until 12 h after a dose of 600 mg. Rifampicin is always used in combination with another antibacterial substance. Results are excellent in most cases. The average duration of antibiotic treatment is 3 months for osteo-arthritis, 6 months for spondylitis and osteitis.

Topics: Adult; Aged; Bone and Bones; Diffusion; Drug Synergism; Female; Hip Prosthesis; Humans; Male; Middle Aged; Osteoarthritis; Rifampin; Staphylococcal Infections

Combination of rifampicin with trimethoprim, erythromycin, tetracycline or fusidic acid have some desirable features in the treatment of difficult infections. They are active against a very wide range of possible pathogens. Resistance to rifampicin is rare. Such combinations may be bactericidal and may be usefully synergistic. They may prevent or delay the emergence of bacterial resistant seen when some single agents are used. They can be used in patients with penicillin hypersensitivity. A series of life-threatening infections has been treated with rifampicin-containing combinations. The infections included endocarditis, meningitis, pneumonia, Legionnaire's disease, and head and neck sepsis. A major reason for the choice of drug was often penicillin hypersensitivity. A second reason was the presumption (mostly subsequently confirmed) that streptococci and/or staphylococci were implicated. The clinical outcome of these infections was generally satisfactory, with few side effects and little evidence of the emergence of antibiotic resistance.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Drug Therapy, Combination; Erythromycin; Female; Fusidic Acid; Humans; Infant; Legionnaires' Disease; Male; Meningitis; Middle Aged; Osteomyelitis; Rifampin; Sepsis; Skin Diseases, Infectious; Staphylococcal Infections; Tetracycline; Trimethoprim

Staphylococcal endocarditis is a condition affecting intravenous drug abusers at increasing rates, and its treatment is still controversial. We used, successfully, high doses of rifampicin, associated with an aminoglycoside, for the treatment of two heroin addicts. In the first we found a left-sided endocarditis with metastatic abscesses in brain, both kidneys, liver and spleen; in the other the finding of bilateral lung abscesses was related to embolic episodes from a diseased tricuspid valve. Since the isolated strains of Staphylococcus aureus were tolerant to methicillin, we used oral rifampicin (20 mg/kg/day) plus an aminoglycoside (amikacin in the former and gentamicin in the latter), after in-vitro testing had proved these combinations to be effective. We achieved, in both cases stable bactericidal concentrations in the serum and a lasting clinical recovery.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Heroin Dependence; Humans; Methicillin; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections

Topics: Adolescent; Female; Heroin Dependence; Humans; Injections, Intravenous; Peritonitis; Pneumonia, Staphylococcal; Rifampin; Staphylococcal Infections; Vancomycin

Activity of eleven antimicrobial agents against methicillin-, methicillin- and rifampin-resistant Staphylococcus aureus was studied using a microtiter broth dilution technique. Coumermycin was the most active agent. Vancomycin, rifampin, fusidic acid and N-formimidoyl-thienamycin showed excellent activity against methicillin-resistant St. aureus (MRSA). Antimicrobial susceptibility pattern was similar for MRSA and methicillin- and rifampin-resistant St. aureus. 8% of MRSA were resistant to trimethoprim and sulfamethoxazole.

Topics: Anti-Bacterial Agents; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Macrophages isolated from the involuted bovine mammary gland were cultured in vitro. Phagocytosis of opsonized Staphylococcus aureus occurred rapidly, but intracellular killing of bacteria was slow. Many intracellular staphylococci survived for up to 4 d exposure to extracellular cloxacillin and emerged from within the macrophages to multiply extracellularly when the antibiotic was inactivated. Rifampicin was significantly more efficient than cloxacillin in killing intracellular S. aureus after 18 h incubation, but it too failed to sterilize the cultures within 3 d. Staphylococci, which had remained viable within macrophages during 20 h incubation with extracellular cloxacillin, showed an increased sensitivity to dilute lysostaphin on subsequent exposure. A 3 d course of intramammary therapy with cloxacillin, commencing simultaneously with an infecting inoculum of approximately 10(8) colony forming units (c.f.u.) S. aureus, apparently eliminated the infection from one quarter of the udders of each of three lactating cows, but bacteria were re-isolated from two cows after a delay of several days. However, when other quarters of the same cows were infected with approximately 10(8) c.f.u. S. aureus which had been phagocytosed by autologous mammary macrophages, similar simultaneous antibiotic therapy failed to affect these infections. The in vitro and in vivo findings indicate the significance of intracellular survival of S. aureus as a factor contributing to failure of antibiotic therapy.

Topics: Animals; Cattle; Cells, Cultured; Cloxacillin; Female; Lysostaphin; Macrophages; Mammary Glands, Animal; Mastitis, Bovine; Penicillin Resistance; Phagocytosis; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Adolescent; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Cloxacillin; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus

The in-vitro inhibitory and bactericidal activities of vancomycin and rifampicin were tested against several Staphylococcus strains recently isolated from clinical material. All strains were first tested for their susceptibility to methicillin, and typed by lyogroup. With vancomycin, minimum inhibitory concentrations (MICs) fell within a narrow range (0.62-2.5 mg/l), and significant differences were not observed both among different lyogroups and between methicillin-sensitive (M-S) and methicillin-resistant (M-R) strains. Minimum bactericidal concentrations (MBCs) of vancomycin either equalled or exceeded by twofold the MICs. With rifampicin, MICs were found to be distributed over a wide range (0.002 to greater than 5 mg/l), and susceptibility appeared to be less in M-R than in M-S isolates. Although MICs greater than or equal to mg/l were only observed in three of the six lyogroups, data appeared insufficient to substantiate definite interspecies differences in staphylococcal susceptibility to rifampicin. MBCs of rifampicin either equalled or exceeded by two- to eightfold the MICs. In-vitro interactions between vancomycin and rifampicin, were investigated both by checkerboard and time-kill tests. By both methods, indifference was observed with the great majority of isolates. Synergism was a rare event, and antagonism was never observed.

Topics: Drug Combinations; Drug Synergism; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

During a hospital outbreak of methicillin-resistant Staphylococcus aureus (MRSA) disease in 30 patients we studied the use of rifampin and trimethoprim/sulfamethoxazole (TMP/SMX) in managing asymptomatic carriers. The outbreak persisted despite control measures including "barrier" precautions, screening cultures, identification of affected persons and rapid hospital discharge of affected patients. The MRSA strain was susceptible to both rifampin and TMP/SMX and in vitro the combination was not antagonistic. Fourteen carriers received a five-day course of rifampin and TMP/SMX given by mouth. Twelve patients were evaluable. Cultures remained persistently positive in four patients, three of whom had foreign bodies that could not be removed. Among the eight with an initial response, two relapsed to the carrier state more than six months after treatment. During the study the outbreak resolved. These data suggest that rifampin and TMP/SMX may decrease the number of MRSA-colonized patients, but may not permanently eradicate the MRSA carrier state.

Topics: Adult; Aged; Carrier State; Cross Infection; Drug Combinations; Drug Therapy, Combination; Humans; Methicillin; Middle Aged; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Selection of rifampicin-resistant Staphylococcus aureus has been described in vitro and in vivo when this compound is given as monotherapy or orally. That this occurrence may be prevented by combination-antibiotic therapy is generally accepted. We report three cases of serious staphylococcal infection treated by a synergic association of rifampicin with either an aminoglycoside or vancomycin. Therapy failed as a result of selection of the same rifampicin-resistant Staphylococcus aureus (serotype and lysotype). These observations may be explained by insufficient diffusion or inactivation of the other antibiotic in the infection site.

Topics: Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mutation; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Rifampicin is used for treating 20 Staphylococcus septic arthritis, in combination with another antibiotic. The former is chosen for its striking bone diffusion. The average duration of the whole antibiotic treatment is 3 months. Rifampicin is usually prescribed, in daily doses of 1 200 mg for 60 days, after one month of parenteral antibiotherapy. The bactericidal activity is controlled regularly by measuring serum inhibitory titre. For 2 patients, the administration of rifampicin is suspended after 12 and 25 days respectively, due to digestive disorders. Results are evaluated at the end of a period averaging 18 months. Articular infection has been cured in all patients. Taking these results into account, we are able to emphasize that the inclusion of rifampicin in the antibiotic scheme is of great value in treating bone and articular infections.

Topics: Adult; Aged; Arthritis, Infectious; Female; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections; Time Factors

10 patients with serious infections caused by Staphylococcus epidermidis (8 cases of endocarditis in non-prosthetic valves, 1 was complicated by osteomyelitis, 1 case of osteomyelitis, and 1 case of septicemia) are described. Clinical and microbiologic features were evaluated including antibiotic sensitivity and synergy studies, phage typing and biotyping. Endocarditis tended to affect the elderly population and the clinical manifestations were quite similar to those caused by Streptococcus viridans. Both patients with osteomyelitis had involvement of the cervical spine with excellent response to antibiotic therapy. The only patient with septicemia acquired via hyperalimentation had delayed clearance of the bacteremia but ultimately responded to intravenous antibiotics. Rifampicin was the most effective of all antibiotics tested. All isolates were sensitive to penicillinase-resistant penicillins and cephalosporins and over half were sensitive to penicillin. Full synergistic activity was demonstrated with cephalothin and nafcillin in combination with rifampicin, and rifampicin-vancomycin was partially synergistic against the majority of the strains. Five of 8 available isolates were non-phage typeable and no definite pattern was established for various types of infections. Four of the 8 isolates were classified as biotype SIIa, 2 biotype SIIc and 2 biotype SVh.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteriological Techniques; Endocarditis, Bacterial; Female; Humans; Male; Middle Aged; Osteomyelitis; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus epidermidis

Topics: Adult; Endocarditis, Bacterial; Female; Humans; Rifampin; Shock, Septic; Staphylococcal Infections; Syndrome

The activities of a range of antibiotics on Staphylococcus aureus organisms that survive within bovine neutrophils in vitro were studied in mice. Cloxacillin, floxacillin, and cephradine failed to kill intracellular staphylococci but increased the organisms' sensitivity to killing by lysostaphin after neutrophil disruption. Fusidate and clindamycin caused an apparent small reduction in viable intraleukocytic S aureus, whereas novobiocin did not demonstrate intracellular activity. Substantial intracellular bactericidal effects were shown in vitro by rifampin and rifamycin SV, even at concentrations in slight excess of the minimum inhibitory concentration. In a mouse model of chronic mastitis, intramammary therapy with rifampin was more effective in reducing viable S aureus in infected glands than was therapy with rifamycin SV.

Topics: Animals; Anti-Bacterial Agents; Cattle; Cloxacillin; Disease Models, Animal; Drug Therapy, Combination; Female; Leukocytes; Lysostaphin; Mastitis; Mastitis, Bovine; Mice; Neutrophils; Penicillin Resistance; Pregnancy; Rifampin; Rifamycins; Rodent Diseases; Staphylococcal Infections; Staphylococcus aureus

The changes in staphylococcal flora induced by antibiotic prophylaxis with rifampin and nafcillin in combination among patients undergoing cardiac valve surgery were compared to those in patients undergoing coronary artery bypass surgery concurrently, who received only cefazolin. Rifampin-nafcillin prophylaxis eradicated carriage of Staphylococcus aureus at a significantly higher rate than did cefazolin (eradicated carriage of 89% vs. 48%, respectively; P less than 0.01); however, by the seventh postoperative day, 75% of the patients receiving rifampin and nafcillin had rifampin-resistant, coagulase-negative staphylococcal perianal floras, compared to 19% of those who received cefazolin (P less than 0.001). Patients receiving rifampin-nafcillin were colonized as frequently (66%) with coagulase-negative staphylococci resistant to gentamicin and methicillin as were those receiving cefazolin (68%). Patients in the coronary intensive care unit who received no antibiotics were infrequently colonized with either rifampin-resistant (none) or gentamicin- and methicillin-resistant (11%) staphylococci. Antibiotic prophylaxis may, therefore, be an important factor in perpetuating the hospital reservoir for antibiotic-resistant, coagulase-negative staphylococci.

Topics: Anti-Bacterial Agents; Cefazolin; Coagulase; Coronary Artery Bypass; Coronary Care Units; Female; Gentamicins; Heart Valve Prosthesis; Humans; Male; Nafcillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus

Topics: Drug Combinations; Humans; Male; Prostatitis; Rifampin; Staphylococcal Infections; Trimethoprim

The authors report a case of legionnaires' disease with retractile late sequelae affecting the lingula and the dorsal segment of the culmen. They stress the need for appropriate and prolonged treatment because of the possible presence of intracellular Legionella pneumophila. The existence of an associated staphylococcal infection is also one of the hypotheses raised in explaining such sequelae.

Topics: Erythromycin; Humans; Legionnaires' Disease; Lung Diseases; Male; Middle Aged; Radiography; Rifampin; Staphylococcal Infections; Time Factors

Vancomycin was used alone and in combination with rifampin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 60 mg of vancomycin/kg of body weight twice a day for 28 days was ineffective in sterilizing infected rabbit bones. Rifampin (40 mg/kg) injected once a day for 28 days sterilized 57% of infected rabbit bones. Treatment with a combination of vancomycin and rifampin for either 14 or 28 days was significantly more effective than either drug used alone, sterilizing 84% and 90%, respectively, of the infected bones of treated animals. A possible explanation for the failure of vancomycin when used alone may be that its in vitro activity against the infecting strain of S. aureus (as measured by minimal inhibitory concentrations or minimal bactericidal concentrations) was substantially less under anaerobic conditions (that is, at partial pressures of oxygen analogous to those in osteomyelitic bones) than under aerobic conditions.

Topics: Animals; Chronic Disease; Drug Therapy, Combination; Female; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The time course of changes in the activity, intensity and completeness of phagocytosis with leukocytes of the peritoneal exudate was studied on mice with experimental staphylococcal infection treated with rifampicin, lincomycin and inactivated staphylococcal vaccine used alone or in combination. It was shown that immunization of the animals with inactivated staphylococcal vaccine promoted stimulation of the phagocytic defense. Rifampicin and lincomycin applied therapeutically induced a decrease in the activity, intensity and completeness of phagocytosis. It should be noted that rifampicin had a less pronounced inhibitory effect than lincomycin. The combined use of vaccine and antibiotics with therapeutic purposes promoted an increase in phagocytosis as compared to the use of the antibiotics alone. The combined therapy sometimes resulted in completeness of phagocytosis making it reach the control values (the 10th and 15th days, rifampicin and vaccine). It should be noted that a more pronounced stimulation of the activity, intensity and completeness of the phagocytosis was observed with the use of the combination of rifampicin and the vaccine.

Topics: Animals; Drug Evaluation, Preclinical; Drug Therapy, Combination; Immunization; Leukocytes; Lincomycin; Mice; Phagocytosis; Rifampin; Staphylococcal Infections; Staphylococcal Vaccines; Time Factors

Topics: Aged; Endocarditis, Bacterial; Humans; Male; Methicillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Vancomycin

Changes in the activity of succinate dehydrogenase (SDH), total and acid phosphatase (TP and AP) were studied in treatment of laboratory animals with rifampicin, lincomycin and with inactivated staphylococcal vaccine used alone or in combinations. It was shown that immunization of the animals with inactivated staphylococcal vaccine under conditions of experimental staphylococcal infection promoted stimulation of the enzyme activity. Rifampicin and lincomycin used for the treatment of such animals lowered the activity of the enzymes. The suppressing effect of the antibiotics increased with an increase in the period of their use. It should be noted that the inhibitory effect of rifampicin on the activity of SDH, TP and AP was less pronounced than that of lincomycin. The combined use of the vaccine and antibiotics for the treatment of the animals promoted an increase in the enzyme activity as compared to the use of the antibiotics alone. Sometimes the activity of SDH, TP and AP reached the control levels in such animals or the levels observed in the animals treated with the vaccine alone. Stimulation of the enzyme activity was more pronounced when the vaccine was used in combination with rifampicin.

Topics: Animals; Drug Evaluation, Preclinical; Drug Therapy, Combination; Lincomycin; Liver; Mice; Phosphoric Monoester Hydrolases; Rifampin; Staphylococcal Infections; Staphylococcal Vaccines; Succinate Dehydrogenase; Time Factors

The survival level of the experimental animals with infection caused by Staphylococcus and Ps. aeruginosa was the highest when the animals were treated with a combination of gentamicin and rifampicin as compared to the use of every antibiotic alone. The combination had a more favourable effect on the plasmocytic reaction and production of the antibody-forming cells in the lymphoid organs which correlated with the therapeutic efficacy of the antibiotics.

Topics: Animals; Antibody-Producing Cells; Drug Evaluation, Preclinical; Drug Therapy, Combination; Gentamicins; Mice; Plasma Cells; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Time Factors

Antibiotic therapy of methicillin-resistant Staphylococcus epidermidis endocarditis was investigated with the rabbit endocarditis model. Time-kill studies in vitro demonstrated that gentamicin and rifampin had the most rapid early bactericidal rates. With rifampin alone, rifampin-resistant subpopulations emerged. Combinations of antibiotics with gentamicin or rifampin in vitro did not significantly alter the killing rate but prevented emergence of subpopulations resistant to the latter. In the rabbit endocarditis model, gentamicin and vancomycin were the most effective single antibiotic regimens in terms of ability to reduce the bacterial densities on cardiac valve vegetations. Five treatment regimens were equally effective, including vancomycin, gentamicin, vancomycin plus rifampin or gentamicin, and rifampin plus gentamicin. The three-drug combination of vancomycin, rifampin, and gentamicin did not significantly improve the results. Cephalothin therapy was significantly less effective than any of the regimens noted above. It was no more effective than no treatment at 2 days and was only slightly more effective at 4 days. This result with cephalothin treatment was not predicted by routine types of in vitro antibiotic susceptibility testing. Treatment of rabbits with methicillin or cephalothin was associated with an increase in the subpopulation of bacteria resistant to the respective drugs. A number of regimens show potential for therapy of these infections, including vancomycin plus rifampin or gentamicin, rifampin plus gentamicin, and vancomycin alone.

Topics: Animals; Anti-Bacterial Agents; Cephalothin; Disease Models, Animal; Drug Therapy, Combination; Endocarditis; Gentamicins; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Vancomycin

Four patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage in one body site each (urine, anterior nares, throat, or wound) received 300 mg of oral rifampin twice daily for ten days. Treatment did not eradicate MRSA carriage in any patient, and three of the posttherapy isolates were highly resistant to the drug. Rifampin by itself does not appear to be an effective drug for the eradication of MRSA carriage.

Topics: Adult; Aged; Female; Humans; Male; Methicillin; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Rifampin; Staphylococcal Infections

An eight-year-old boy developed staphylococcal endocarditis. He was treated initially with nafcillin and gentamicin, but he remained febrile. The minimum bactericidal concentration (MBC) of nafcillin was 130 times the minimum inhibitory concentration (MIC). Following the addition of rifampin to the antibiotic regimen, the patient became afebrile and recovered. The discrepancy between the MBC and MIC indicated tolerance to nafcillin. Tolerance is a mode of antibiotic resistance that must be considered in treating life-threatening illness.

Topics: Child; Drug Tolerance; Endocarditis, Bacterial; Humans; Male; Nafcillin; Rifampin; Staphylococcal Infections

Rifampicin plus trimethoprim (rifaprim) was used to treat 20 patients with chronic prostatitis in exacerbation: 11 received 2 tablets at bedtime for 15 days followed by 1 tablet at bedtime for another 105 days, and 9 received 1 tablet in the morning and 2 tablets at bedtime for 15 days, then 2 tablets at bedtime for 15 days followed by 1 tablet at bedtime for another 90 days. All patients had an enlarged tender prostate and all but 2 were symptomatic. In 10 patients previous treatment, including co-trimoxazole in 5, had failed. Cultures of the expressed prostatic secretions yielded Staphylococcus aureus in 17 patients and gram-negative micro-organisms in 3. At the end of treatment 6 of 11 patients given the lower dosage were cured clinically and bacteriologically compared to 8 of 9 given the higher dosage. After 2 to 3 years of following 5 of 9 patients in the first group and all 7 in the second group had not suffered relapse. From our study it is evident that rifaprim is a potent drug in the treatment of chronic prostatitis caused mainly by Staphylococcus aureus. A promptness of therapeutic response and the rate of cure at the end of treatment as well as after at least 2 years of followup favor the higher drug dosage.

Topics: Adult; Chronic Disease; Drug Combinations; Humans; Male; Middle Aged; Prostatitis; Rifampin; Staphylococcal Infections; Trimethoprim

Strains of methicillin-resistant Staphylococcus aureus are resistant to other penicillins. The in-vitro susceptibility to the cephalosporins differs among strains. Some strains, susceptible to cephalosporins by the standard disk susceptibility test, are proved resistant by the quantitative dilution test; they may show pop-up colonies within the zone of inhibition when incubated further at room temperature. The clinical efficacy of the cephalosporins with or without an aminoglycoside in treating infections due to methicillin-resistant S. aureus is in doubt. To date, susceptible to vancomycin. In-vitro antagonism of vancomycin and rifampin against S. aureus has been shown. Thus, vancomycin alone appears to be the treatment of choice; if this treatment fails, aminoglycoside or rifampin should be added. Serum bactericidal titers should be carefully monitored before and after the addition of the new agent and in-vitro time-kill studies of combination of antibiotics done if feasible.

Topics: Cephalosporins; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

We investigated rifampin and cefazolin sodium as prophylactic agents in a dog model of vascular graft infection. A 1-cm segment of 3-mm-diameter polytetrafluoroethylene (Gore-tex) graft was sewn into the right carotid artery of each dog, and prior to closure, 10(3) Staphylococcus organisms sensitive to both cefazolin and rifampin were injected over the graft. The dogs were killed five days after surgery and the grafts cultured. Infection occurred in 100% of controls, 58% of cefazolin-pretreated dogs, and 17% of rifampin-pretreated dogs. Mean blood levels of antibiotics were assayed as follows: cefazolin, 50.1 micrograms/mL; rifampin, 2.9 micrograms/mL. Both were well above the minimal inhibitory concentration. Thus, rifampin proved to be more effective than cefazolin in this animal model.

Topics: Animals; Blood Vessel Prosthesis; Cefazolin; Dogs; Premedication; Rifampin; Staphylococcal Infections; Surgical Wound Infection

Topics: Animals; Anti-Bacterial Agents; Male; Methicillin; Mice; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Vancomycin

Topics: Cephalexin; Cephalothin; Clindamycin; Cloxacillin; Endocarditis, Bacterial; Gentamicins; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections

Staphylococcus epidermidis ventriculitis developed in a patient undergoing treatment for meningeal lymphoblastic lymphoma via Ommaya subcutaneous reservoir. Treatment with a regimen of intravenous and intraventricular vancomycin and oral rifampin resulted in prompt cure of the infection without removal of the reservoir. The antibiotic therapy, guided by CSF bacteriocidal levels, was convenient to administer, nontoxic, and well tolerated. No interruption of lymphoma treatment was necessary.

Topics: Adult; Brain Diseases; Cerebral Ventricles; Drug Implants; Drug Therapy, Combination; Humans; Lymphoma; Male; Meningeal Neoplasms; Rifampin; Staphylococcal Infections; Vancomycin

During the period 1965-79 191 cystic fibrosis patients have been treated with 2349 course of anti-staphylococcal chemotherapy in the Danish Cystic Fibrosis Centre. The standard treatment was orally administered Fusidic acid in combination with Oxacillin or Dicloxacillin given for 14 days. In cases of penicillin allergy Fusidic acid in combination with Rifampicin was given. The overall results showed that S. aureus was eradicated from sputum by a single course of chemotherapy in 74% of the cases, although in 8% the original strains (phage-type) was replaced by a new strain. Repeated or extended treatment was successful in most of the remaining cases and, as a result, only 9% of our patients harboured S. aureus continuously for 6 months or more. On the average each patient received 2 anti-staphylococcal treatment per year, but no decrease in efficacy of repeated treatment was seen. Likewise, no significant increase of S. aureus precipitins and no development of resistant strains was seen in our patients. Due to the efficacy of chemotherapy and the principles of early treatment whether there are clinical symptoms of infection or not, S. aureus infection is now considered a minor problem without relation to poor prognosis in our cystic fibrosis patients.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Dicloxacillin; Female; Fusidic Acid; Humans; Infant; Male; Oxacillin; Probenecid; Pseudomonas Infections; Rifampin; Staphylococcal Infections

By the time-kill method, the combinations of nafcillin plus rifampin and oxacillin plus rifampin were antagonistic against 20 strains of Staphylococcus aureus. No synergism was demonstrated.

Topics: Drug Therapy, Combination; Microbial Sensitivity Tests; Nafcillin; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Cerebral Ventricles; Encephalitis; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Rifampin; Staphylococcal Infections

Cloxacillin effectively killed Staphylococcus aureus in vitro and in experimental acute mastitis in the mouse, but was ineffective in reducing bacterial counts in those with experimental chronic mastitis. Rifampicin was similarly bactericidal for staphylococci in vitro and in acute mastitis but it also significantly reduced numbers of viable bacteria in chronic mastitis. Exposure of multiplying staphylococci in vitro and in vivo to rifampicin alone led to the emergence of resistant bacteria, but this was prevented by the use of a combination of rifampicin with cloxacillin. This combination showed neither antagonism nor synergy in vitro, was more effective than either antibiotic alone in acute mastitis and killed S aureus in the chronic infection as effectively as rifampicin alone.

Topics: Animals; Cloxacillin; Drug Therapy, Combination; Female; Mammary Glands, Animal; Mastitis; Mice; Penicillin Resistance; Pregnancy; Rifampin; Staphylococcal Infections; Staphylococcus aureus

A 69-year-old man with chronic renal failure maintained on twice weekly hemodialysis had infection of the vascular access graft with bacteremia due to Staphylococcus aureus. Despite serum vancomycin levels that greatly exceeded the mean inhibitory and bactericidal concentrations, he failed to respond and rifampin was added. The bacteremia promptly cleared, but the patient died suddenly eight days later. Autopsy showed an acute arteritis of the graft with intracellular gram-positive organisms; two splenic blood cultures grew S aureus. Although previous investigators have shown that the combination of vancomycin and rifampin may be effective in some cases of S aureus endocarditis this antibiotic combination should not be used routinely unless in vitro synergy is demonstrated.

Topics: Aged; Arteriovenous Shunt, Surgical; Drug Synergism; Drug Therapy, Combination; Humans; Male; Renal Dialysis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

By the time-kill method, vancomycin and rifampin were antagonistic against 43 of 50 strains of Staphylococcus aureus, whether susceptible or resistant to methicillin.

Topics: Drug Interactions; Drug Therapy, Combination; Humans; Methicillin; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Three patients with Staphylococcus epidermis meningitis associated with cerebrospinal fluid (CSF) shunt devices were treated with a combination of intravenous vancomycin and oral rifampin. Two of the isolates were methicillin-resistant. All patients had a favorable clinical response. Time-kill curves showed that the addition of rifampin to vancomycin resulted in enhanced bactericidal activity against all isolates when compared to either antibiotic alone. This finding suggests that the combination of oral rifampin and intravenous vancomycin may be useful in the treatment of methicillin-resistant and recalcitrant methicillin-sensitive S. epidermis meningitis associated with CSF shunts. In vitro susceptibility testing should be performed.

Topics: Aged; Cerebrospinal Fluid Shunts; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Meningitis; Rifampin; Staphylococcal Infections; Vancomycin

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infusions, Parenteral; Male; Middle Aged; Rifampin; Staphylococcal Infections; Tuberculosis; Tuberculosis, Pulmonary

Twenty clinical isolates of Staphylococcus aureus were examined to determine the frequency of rifampin-resistant variants. All isolates were highly susceptible to rifampin, with mean minimum inhibitory concentrations of 0.11 +/- 0.1 microgram/ml and mean minimum bactericidal concentrations of 0.22 +/- 0.2 microgram/ml. The frequency of isolation of resistant variants was similar to all rifampin concentrations tested. Rifampin-resistant variants maintained their resistance upon daily subculture in rifampin-free broth. Rifampin-susceptible S. aureus exhibited a growth and survival advantage over the rifampin-resistant mutants both in pure cultures and in mixtures with rifampin-resistant antecedents. A comparison of the virulence for mice of five susceptible isolates and their 100 microgram/ml-rifampin-resistant variants showed that two of the resistant variants were less virulent than the susceptible strains via intraperitoneal challenge, whereas three of the resistant variants were less virulent by intravenous challenge (P less than 0.05).

Topics: Animals; Drug Resistance, Microbial; Female; Mice; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Rifampin is a potentially useful anti-staphylococcal agent, but resistance develops frequently when the drug is used alone. The efficacy of rifampin, trimethoprim, and a penicillin alone or in combination was examined in mice with acute or subacute infections. Mice were infected intraperitoneally with penicillin-susceptible Staphylococcus aureus. Survival after penicillin therapy was only 9.1% in contrast to survival after rifampin therapy which was 68% (P less than 0.001). No rifampin-resistant S. aureus were isolated from peritoneal fluid or heart blood samples from dead animals in these short-term experiments. Rifampin was ineffective (survival, 4.8%) for infections instituted with rifampin-resistant strains. Long-term experiments were conducted after intravenous injection of 4 x 10(8) S. aureus. Forty percent of the animals survived after methicillin therapy; 77% survived after rifampin therapy (P less than 0.001). However, 40% of those animals that died after rifampin therapy died with rifampin-resistant organisms. No animal dying in groups treated with a combination of rifampin and trimethoprim (85% survival) or rifampin and methicillin (79% survival) died with rifampin-resistant organisms. Thus, rifampin combined with a penicillin or trimethoprim was effective in preventing the development of rifampin-resistant strains.

Topics: Acute Disease; Animals; Drug Synergism; Drug Therapy, Combination; Male; Methicillin; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Rifampin; Staphylococcal Infections; Trimethoprim

Topics: Animals; Ascitic Fluid; Cephalothin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; In Vitro Techniques; Macrophages; Male; Mice; Penicillin G; Phagocytosis; Rats; Rats, Inbred Strains; Rifampin; Staphylococcal Infections

Staphylococcus epidermidis endocarditis occurred four days following aortic valve replacement with a Björk-Shiley prosthesis. Antimicrobial therapy, shown to be effective by in vitro and in vivo studies, failed to eradicate the infection. When rifampin was added to the existing antibiotic regimen, peak serum bactericidal activity increased, the patient defervesced, and blood cultures became negative.

Topics: Adult; Aortic Valve; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Postoperative Complications; Rifampin; Staphylococcal Infections

Topics: Cerebrospinal Fluid Shunts; Humans; Rifampin; Staphylococcal Infections; Surgical Wound Infection

Topics: Animals; Anti-Bacterial Agents; Cattle; Cattle Diseases; Dog Diseases; Dogs; Goats; Humans; Rifampin; Staphylococcal Infections; Streptomycin; Surgical Wound Infection

Rifampin and trimethoprim were used alone and in combination in the treatment of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Rifampicin levels in infected bone were well above the minimum inhibitory concentration of the infecting strain of S. aureus for at least 4 h after injection. In contrast, trimethoprim levels in diseased bone were below the minimum inhibitory concentration as early as 1 h after injection. Trimethoprim or rifampin, administered alone for 14 days, were ineffective in sterilizing infected rabbit bones. The combination of rifampin plus trimethoprim was significantly more effective (P less than 0.005) than either agents given alone for a comparable duration of time. Staphylococci isolated from the bones of rabbits treated with rifampin alone or rifampin plus trimethoprim were uniformly resistant to rifampin, but retained their susceptibility to trimethoprim.

Topics: Administration, Oral; Animals; Bone and Bones; Drug Therapy, Combination; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Trimethoprim

Topics: Adult; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Rifampin; Staphylococcal Infections; Vancomycin

Antibiotic prophylaxis for the prevention of endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a modified rabbit endocarditis model and compared with results obtained with methicillin-sensitive S. epidermidis (MSSE). One dose of nafcillin, cefamandole, cephalothin, or vancomycin neither prevented endocarditis nor sterilized the blood of rabbits challenged with each of two MRSE or two MSSE isolates. One dose of gentamicin protected greater than or equal to 80% of animals challenged with three of the four isolates, and one dose of rifampin protected greater than or equal to 90% challenged with any of the four isolates. Multiple doses of any of the antibiotics prevented endocarditis in greater than or equal to 80% of rabbits challenged with MSSE, and four doses of vancomycin protected rabbits challenged with MRSE. However, MRSE endocarditis was prevented in less than or equal to 25% of animals given six doses of nafcillin or cephalosporins. Thus, nafcillin and cephalosporins were ineffective prophylaxis for MRSE endocarditis, whereas vancomycin, gentamicin, and rifampin were effective.

Topics: Animals; Anti-Bacterial Agents; Cefamandole; Cephalothin; Endocarditis, Bacterial; Female; Gentamicins; Male; Methicillin; Nafcillin; Penicillin Resistance; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

The persistence of staphylococcal arthritis in a patient treated with nafcillin was attributed to intracellular sequestration of staphylococci. These intraphagocytic organisms were protected against bactericidal activity. The infection was cleared by rifampin--an agent which can penetrate leucocyte membranes. When clinical infections do not respond to seemingly adequate antimicrobial treatment, intracellular persistence of bacteria should be considered.

Topics: Adult; Arthritis, Infectious; Elbow Joint; Humans; Knee Joint; Male; Nafcillin; Penicillin Resistance; Phagocytosis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Synovial Fluid

Topics: Cerebrospinal Fluid Shunts; Coagulase; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Rifampin; Staphylococcal Infections; Staphylococcus; Surgical Wound Infection

Two children with persistent bacteremia and endocarditis due to Staphylococcus aureus failed to respond to vancomycin therapy, even though serum levels greatly exceeded the inhibitory concentrations. The Staphylococcus from one patient was resistant to methicillin; the other patient had a penicillin hypersensitivity. There was a wide disparity between the minimum inhibitory and the minimum bactericidal concentrations of vancomycin. Striking clinical and laboratory evidence of improvement was demonstrated with the addition of rifampin therapy.

Topics: Blood; Child, Preschool; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Humans; Infant; Male; Methicillin; Penicillin Resistance; Rifampin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Three patients with bacterial endocarditis (one case due to Staphylococcus aureus and two to S epidermidis) failed to improve on standard therapeutic regimens which were judged adequate by in vitro testing for sensitivity. Rifampin was added to the regimen in each case and resulted in increased bactericidal activity in the serum, sterilization of the cardiac valves, and clinical cure. The apparent clinical success that was achieved suggests that further investigation of the effectiveness of therapy with rifampin in selected cases of staphylococcal endocarditis is warranted.

Topics: Adult; Endocarditis, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Oxacillin; Rifampin; Staphylococcal Infections; Vancomycin

Rifampin was added to existing antibiotic regimens in two patients with Staphylococcus epidermidis infections; one patient had prosthetic valve endocarditis and the other had an infection of a CSF shunt. The addition of rifampin increased serum or CSF bactericidal titers 16-fold or greater and was correlated with a favorable clinical response. The results of tests for tube-dilution antibiotic susceptibility showed rifampin to be the most active of all antibiotics tested against the patients' organisms. The combinations of gentamicin sulfate, nafcillin sodium, or vancomycin hydrochloride with rifampin prevented the emergence of rifampin resistance in vitro and promoted enhanced killing when compared with either antibiotic alone.

Topics: Adolescent; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Drug Synergism; Endocarditis, Bacterial; Female; Gentamicins; Heart Valve Prosthesis; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Nafcillin; Postoperative Complications; Rifampin; Staphylococcal Infections; Staphylococcus; Vancomycin

Studies on the chemotherapeutic action of rifampicin in treatment of staphylococcal sepsis and sepsis caused by gramnegative organisms showed its high efficacy only in treatment of the staphylococcal infection. By the level of its efficacy rifampicin was much superior to benzylpenicillin and especially tetracycline. No difference in the activity level of the antibiotic in treatment of staphylococcal infections caused by sensitive and multiple resistant staphylococcal strains was found. In treatment of the infections caused by gramnegative organisms the drug activity was moderate.

Topics: Acute Disease; Animals; Bacterial Infections; Chronic Disease; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Escherichia coli Infections; Mice; Moscow; Proteus Infections; Pseudomonas Infections; Rifampin; Staphylococcal Infections

The rate at which various antimicrobial agents eradicated Staphylococcus aureus from cardiac vegetations in a rabbit model of endocarditis was studied. The rate at which various drugs and combinations killed high titers of bacteria in broth correlated with the relative effectiveness of the agents in vivo. Gentamicin plus penicillin proved to be synergistic in vitro and more effective in eradicating bacteria from cardiac vegetations in vivo than was penicillin alone. Vancomycin killed bacteria at a rate similar to that for the combination of penicillin and gentamicin, and the rate for cefazolin was similar to that for penicillin alone. Clindamycin was less effective in vivo and in vitro than penicillin. Therapy with rifampin led to the emergence of resistant organisms, and, when penicillin, this drug was less effective in vitro and in vivo than was penicillin alone. This model appears to offer an effective method for evaluation of antimicrobial treatment of staphylococcal endocarditis.

Topics: Animals; Anti-Bacterial Agents; Cephalothin; Clindamycin; Disease Models, Animal; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Penicillins; Rabbits; Rifampin; Staphylococcal Infections; Time Factors; Vancomycin

Topics: Aminosalicylic Acids; Drug Resistance, Microbial; Drug Therapy, Combination; England; Humans; Isoniazid; Rifampin; Staphylococcal Infections; Streptomycin; Substance-Related Disorders; Tuberculosis

Topics: Animals; Bacteria; Bacterial Infections; Bordetella; Drug Evaluation, Preclinical; Enterococcus faecalis; Escherichia coli; In Vitro Techniques; Klebsiella pneumoniae; Listeria monocytogenes; Listeriosis; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Proteus Infections; Proteus mirabilis; Proteus vulgaris; Pseudomonas aeruginosa; Rifampin; Salmonella typhimurium; Sarcina; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Streptococcus pneumoniae

Topics: Animals; DNA, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacter; Escherichia coli; Escherichia coli Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Nalidixic Acid; Proteus vulgaris; Pseudomonas aeruginosa; Rifampin; Salmonella enteritidis; Salmonella typhi; Shigella flexneri; Shigella sonnei; Staphylococcal Infections; Staphylococcus

Topics: Ampicillin; Arthritis, Rheumatoid; Fusidic Acid; Humans; Lincomycin; Male; Middle Aged; Penicillin Resistance; Potassium; Rifampin; Sepsis; Staphylococcal Infections; Urea

Topics: Administration, Oral; Child; Endocarditis, Bacterial; Erythromycin; Humans; Male; Rifampin; Staphylococcal Infections

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Chloramphenicol; Chlortetracycline; Dihydrostreptomycin Sulfate; Drug Stability; Erythromycin; Gastric Juice; Hydrogen-Ion Concentration; Kanamycin; Male; Mice; Microbial Sensitivity Tests; Novobiocin; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rifampin; Solutions; Staphylococcal Infections; Staphylococcus; Streptococcal Infections

Topics: Anti-Bacterial Agents; Cephaloridine; Chloramphenicol; Erythromycin; Fusidic Acid; Humans; Kanamycin; Leucomycins; Lincomycin; Microbial Sensitivity Tests; Mongolia; Neomycin; Oxacillin; Penicillin Resistance; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus; Streptomycin; Tetracycline; Vancomycin

Bacteria surviving within leukocytes are protected from the lethal action of high concentrations of most antibiotics, which may explain, in part, the failure of bactericidal antibiotics to eradicate staphylococci from abscesses. Since rifampin is unique in its ability to kill intraleukocytic bacteria, the efficacy of this drug was tested in the treatment of staphylococcal infections in mice. Groups of mice infected intravenously with Staphylococcus aureus were treated with rifampin (20 mg/kg), procaine penicillin (937.5 mg/kg), or methicillin (200 mg/kg). All untreated mice died with disseminated visceral abscesses. After 10 days of therapy, survival in groups treated with penicillin and methicillin was 16 and 20%, respectively, whereas with rifampin it was 80% (P < 0.0005). Antibiotic concentrations in the serum of mice treated with penicillin, methicillin, or rifampin were bactericidal for the strain of S. aureus used. Serial bacterial counts of kidney, lung, and spleen homogenates showed that neither penicillin nor methicillin was able to eradicate staphylococci, whereas rifampin completely sterilized those organs in many mice. When abscess contents and infected peritoneal washings were incubated with high concentrations of penicillin, methicillin, or rifampin, only rifampin killed all of the bacteria. The capacity of rifampin to eradicate staphylococci from pus in vitro and from abscesses in mice appears to be related to the ability of rifampin to kill intraleukocytic bacteria.

Topics: Animals; Exudates and Transudates; Male; Mice; Mice, Inbred Strains; Rifampin; Staphylococcal Infections; Time Factors

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloglycin; Cephalosporins; Enterobacteriaceae Infections; Gentamicins; Humans; Pseudomonas Infections; Rifampin; Staphylococcal Infections

Topics: Abscess; Animals; Leukocytes; Mice; Microbial Sensitivity Tests; Phagocytosis; Rifampin; Staphylococcal Infections; Staphylococcus

Topics: Animals; Cephaloridine; Escherichia coli; Escherichia coli Infections; Infections; Klebsiella; Klebsiella Infections; Listeria monocytogenes; Listeriosis; Mice; Pasteurella; Pasteurella Infections; Pneumococcal Infections; Rifampin; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus; Streptococcus pneumoniae

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cephaloridine; Cephalothin; Chloramphenicol; Cross Infection; Erythromycin; Erythromycin Ethylsuccinate; Humans; Kanamycin; Lincomycin; Methicillin; Microbial Sensitivity Tests; Oxacillin; Penicillin Resistance; Penicillins; Personnel, Hospital; Rifampin; Staphylococcal Infections; Staphylococcus; Streptomycin; Tetracycline

Topics: Animals; Cattle; Drug Resistance, Microbial; Female; Injections; Mammary Glands, Animal; Mastitis, Bovine; Milk; Rifampin; Staphylococcal Infections; Streptococcal Infections

Topics: Animals; Drug Synergism; Erythromycin; Methicillin; Rabbits; Rifampin; Staphylococcal Infections

Topics: Animals; Bacteria; Drug Resistance, Microbial; Escherichia coli Infections; Mice; Microbial Sensitivity Tests; Nalidixic Acid; Piperidines; Rifampin; Staphylococcal Infections

Topics: Acute Disease; Adult; Chronic Disease; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Proteus Infections; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Adult; Empyema; Humans; Male; Middle Aged; Rifampin; Staphylococcal Infections

Topics: Bronchial Diseases; Chloramphenicol; Humans; Lung Diseases; Microbial Sensitivity Tests; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Streptococcal Infections; Tetracycline

Topics: Chronic Disease; Humans; Infections; Nitrogen; Pneumococcal Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Tuberculosis, Pulmonary; Urinary Tract Infections

Topics: Ampicillin; Animals; Drug Stability; Escherichia coli; Escherichia coli Infections; Hydrogen-Ion Concentration; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus

Topics: Anti-Bacterial Agents; Erythromycin; Humans; Kanamycin; Lincomycin; Novobiocin; Oxacillin; Penicillin Resistance; Rifampin; Staphylococcal Infections; Staphylococcus; Time Factors

Topics: Animals; Dermatomycoses; Drug Resistance, Microbial; Enterobacteriaceae Infections; Guinea Pigs; Humans; Male; Microbial Sensitivity Tests; Prostatitis; Pyoderma; Rabbits; Rats; Rifampin; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Urethritis; Urinary Tract Infections

Topics: Antitubercular Agents; Humans; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Staphylococcus; Tuberculosis, Pulmonary; Urinary Tract Infections

Topics: Administration, Topical; Anti-Infective Agents, Local; Anti-Inflammatory Agents; Female; Humans; Male; Ointments; Prednisolone; Rifampin; Skin Diseases, Infectious; Skin Tests; Staphylococcal Infections

Topics: Ampicillin; Animals; Bacillus; Bacteria; Brucella; Cephaloridine; Clostridium perfringens; Enterobacteriaceae; Haemophilus influenzae; Mice; Micrococcus; Mycobacterium; Neisseria; Pasteurella; Pseudomonas; Rifampin; Sarcina; Staphylococcal Infections; Staphylococcus; Streptococcus; Streptococcus pneumoniae; Tetracycline

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Endocarditis, Bacterial; Erythromycin; Female; Fusidic Acid; Humans; Infant; Infant, Newborn; Male; Methicillin; Middle Aged; Novobiocin; Penicillin Resistance; Pneumonia, Staphylococcal; Rifampin; Sepsis; Staphylococcal Infections

Topics: Adolescent; Adult; Bone Diseases; Central Nervous System Diseases; Female; Humans; Injections, Spinal; Male; Middle Aged; Neurosurgery; Pneumococcal Infections; Rifampin; Skin Diseases; Staphylococcal Infections

Topics: Anti-Infective Agents, Local; Carrier State; Chloramphenicol; Cloxacillin; Cross Infection; Erythromycin; Humans; Lincomycin; Oxytetracycline; Penicillin G; Penicillin Resistance; Rifampin; Staphylococcal Infections; Surgical Wound Infection

Topics: Child; Female; Humans; Lung Diseases; Osteomyelitis; Penicillins; Rifampin; Staphylococcal Infections

Topics: Biliary Tract Diseases; Cholecystitis; Humans; Rifampin; Staphylococcal Infections

Topics: Animals; Mice; Rifampin; Staphylococcal Infections; Tuberculosis

Topics: Adolescent; Adult; Aged; Bacteria; Female; Humans; In Vitro Techniques; Infant; Male; Middle Aged; Rifampin; Staphylococcal Infections; Staphylococcus; Surgical Wound Infection

Topics: Animals; Chemical Phenomena; Chemistry; In Vitro Techniques; Mice; Oxides; Rifampin; Staphylococcal Infections

Topics: Animals; Blood; Humans; In Vitro Techniques; Mice; Pneumococcal Infections; Rifampin; Staphylococcal Infections; Streptococcal Infections; Urine