rifampin and Bacterial-Infections

Rifampin was initially approved for the treatment of tuberculosis. Because of its low toxicity, broad-spectrum activity, and good bioavailability, rifampin is now commonly administered as combination antimicrobial therapy for the treatment of various infections caused by organisms other than mycobacteria. This review summarizes the most recent clinical studies on the use of rifampin combinations for treating four common non-mycobacterial infections: acute bacterial meningitis, infective endocarditis and bacteraemia, pneumonia, and biofilm-related infections.. We performed a literature search of clinical studies published in English from January 2005 to June 2016 using the PubMed database with the search terms "rifampin" with "meningitis" or "infective endocarditis and bacteraemia" or "pneumonia" or "prosthetic joint infections.. Current evidence to support a rifampin combination therapy as a treatment for non-mycobacterial infections was largely based on in vitro/in vivo studies and non-comparable retrospective case series. Additionally, controlled clinical trials that directly compared outcomes resulting from rifampin treatment versus treatment without rifampin were limited.. Rifampin combination therapy appears promising for the treatment of non-mycobacterial infections. However, further definitive clinical trials are necessary to validate its use because the risk of adverse drug-drug interactions and of the emergence of rifampin resistance during treatment may outweigh the potential benefits.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Mycobacterium Infections; Rifampin

Animal infection models in the pharmacokinetic/pharmacodynamic (PK/PD) evaluation of antimicrobial therapy serve an important role in preclinical assessments of new antibiotics, dosing optimization for those that are clinically approved, and setting or confirming susceptibility breakpoints. The goal of animal model studies is to mimic the infectious diseases seen in humans to allow for robust PK/PD studies to find the optimal drug exposures that lead to therapeutic success. The PK/PD index and target drug exposures obtained in validated animal infection models are critical components in optimizing dosing regimen design in order to maximize efficacy while minimize the cost and duration of clinical trials. This review outlines the key components in animal infection models which have been used extensively in antibiotic discovery and development including PK/PD analyses.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Disease Models, Animal; Microbial Sensitivity Tests

Implant-associated infection is caused by surface-adhering bacteria persisting as biofilm. Periprosthetic joint infection is difficult to diagnose and treat. The high susceptibility of implanted devices to infection is because of a locally acquired host defense defect, and persistence is mainly because of the rapid formation of a biofilm resistant to host defense and antimicrobial agents. Successful treatment of periprosthetic joint infection requires the optimal surgical procedure combined with long-term antimicrobial therapy directed against surface-adhering microorganisms. Surgical treatment according to an algorithm has been validated in several observational studies. The role of rifampin against device-associated staphylococcal infection has been evaluated in an animal model, in observational studies and in a controlled trial. Given the limited efficacy of traditional antibiotics in implant-associated infections, novel strategies such as coating of the device, vaccination against biofilms, and quorum-sensing inhibitors are promising future options for prevention and treatment.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Biofilms; Disease Models, Animal; Humans; Joint Prosthesis; Prosthesis-Related Infections; Randomized Controlled Trials as Topic; Rifampin; Treatment Outcome

The first antibiotic of the ansamycin family, rifampicin (RIF), was isolated in 1959 and was introduced into therapy in 1962; it is still a first-line agent in the treatment of diseases such as tuberculosis, leprosy and various biofilm-related infections. The antimicrobial activity of RIF is due to its inhibition of bacterial RNA polymerase (RNAP). Most frequently, bacteria become resistant to RIF through mutation of the target; however, this mechanism is not unique. Other mechanisms of resistance have been reported, such as duplication of the target, action of RNAP-binding proteins, modification of RIF and modification of cell permeability. We suggest that several of these alternative resistance strategies could reflect the ecological function of RIF, such as autoregulation and/or signalling to surrounding microorganisms. Very often, resistance mechanisms found in the clinic have an environmental origin. One may ask whether the introduction of the RIF analogues rifaximin, rifalazil, rifapentine and rifabutin in the therapeutic arsenal, together with the diversification of the pathologies treated by these molecules, will diversify the resistance mechanisms of human pathogens against ansamycins.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Ecology; Genes, Bacterial; Humans; Rifampin; Selection, Genetic

Intestinal epithelium, mucosal immune system, and bacterial flora represent a morpho-functional system on dynamic balance responsible for the intestinal metabolic and trophic functions, and the regulation of mucosal and systemic host's immunity. Obesity is a pathological condition affecting a growing number of people especially in the Western countries resulting from the failure of the organism's energetic balance based on the perfect equality of income, waste, and storage. Recent evidences explain the mechanisms for the microbial regulation of the host's metabolism both in health and disease. In particular, animal studies have explained how quali-/quantitative changes in microflora composition are able to affect the absorption of the nutrients and the energy distribution. Antibiotics, prebiotics, probiotics, and symbiotics are the instruments utilized in the current clinical practice to modulate the intestinal bacterial flora in man both in health and pathologic conditions with promising preliminary results on prevention and therapy of obesity and related metabolic diseases.

Topics: Antibiotics, Antitubercular; Bacterial Infections; Humans; Intestinal Mucosa; Intestines; Metabolic Diseases; Metagenome; Obesity; Probiotics; Rifampin; Stomach

Topics: Antibiotics, Antitubercular; Bacterial Infections; Child; Drug Therapy, Combination; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Tuberculosis

This article discusses three classes of antibacterial agents that are uncommonly used in bacterial infections (other than mycobacterial infections) and can be thought of as special-use agents. These are the polymyxins, rifampin, and the aminoglycosides.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Humans; Polymyxins; Rifampin

Infection of penile prostheses, estimated to occur in 3% of cases, represent the major complication of this type of prosthesis. Early sepsis occurs during the first week and presents in the form of frank clinical features (pain, erythema, penile discharge); highly virulent bacteria are isolated, such as Staphylococcus aureus. Late sepsis occurs after an interval of several weeks to several months with less specific clinical features; Staphylococcus epidermidis is isolated in more than 50% of cases. Conventional treatment of these infections consists of antibiotics adapted to the local flora and removal of the prosthesis, sometimes followed by deferred reimplantation. Prosthetic material salvage procedures are now proposed. Patient-related risk factors for infection include diabetes, urinary tract infection and immunodepression, while procedure-related risk factors include the length of hospital stay, poor operative technique, prolonged operating time and iatrogenic urethral injuries. Prevention of sepsis of penile prostheses is based on prevention of these risk factors and prophylactic antibiotics or prolonged antibiotic therapy.

Topics: Bacterial Infections; Diabetes Complications; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Penile Prosthesis; Penis; Postoperative Complications; Rifampin; Risk Factors; Vancomycin

Rifampin has limited use in monotherapy because of the rapid development of resistance. In combination therapy with a variety of antimicrobials, it has many applications for treatment of serious infections.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Infections; Drug Therapy, Combination; Humans; Mycoses; Rifampin; Tuberculosis

Vascular catheters impregnated with antimicrobial agents have been shown to decrease the risk of catheter-related colonization and bloodstream infections. Various antimicrobials and antiseptics have been used. In a recent meta-analysis of 12 studies, catheters coated with chlorhexidine and silver sulfadiazine (CH/SS) were shown to be significantly less likely to be associated with catheter-related bloodstream infections than uncoated catheters. However, these catheters were coated only on the external surface and they are associated with short antimicrobial durability (3-7 days). In addition, anaphylactic reactions to them were reported in Japan. Vascular catheters impregnated with minocycline and rifampin (M/R) were found to be highly efficacious in preventing catheter-related infections. In a recent prospective, randomized trial, the likelihood of catheter-related bloodstream infections associated with the use of M/R catheters was one-twelfth of that observed with catheters coated with CH/SS. The M/R catheters are coated on the external and internal surfaces and have an antimicrobial durability of 4 weeks. Although no resistance to either minocycline or rifampin has been seen in two trials, further studies are required to determine whether the risk of resistance outweighs the benefits derived from their use. In conclusion, antimicrobial catheters have been shown to be highly cost effective in decreasing the risk of catheter-related bloodstream infection.

Topics: Anaphylaxis; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Local; Bacteremia; Bacterial Infections; Catheters, Indwelling; Chlorhexidine; Coated Materials, Biocompatible; Enzyme Inhibitors; Humans; Minocycline; Rifampin; Risk Assessment; Risk Factors; Silver Sulfadiazine

Rifampin has very broad antimicrobial properties with in vitro activities against many bacteria, mycobacteria, higher bacteria, chlamydia, fungi, parasites, and viruses (Table 1). The clinical use of rifampin is more limited, in part because of the lack of in vivo human clinical studies demonstrating its efficacy. Investigators have valid concerns regarding the emergence of resistance of mycobacteria if widespread use of rifampin becomes common, although this has not been well documented. Because rifampin obtains therapeutic levels intracellularly and is distributed widely throughout the body, the antibiotic potentially could be used on a broader scale, but more studies will be needed to demonstrate its clinical utility.

Topics: Animals; Bacterial Infections; Humans; Rifampin

Topics: Adult; Bacterial Infections; Child; Drug Combinations; Humans; Isoniazid; Rifampin; Tuberculosis

Topics: Age Factors; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Drug Combinations; Erythromycin; Humans; Infant; Nitrofurantoin; Penicillins; Rifampin; Sulfamethoxazole; Sulfisoxazole; Trimethoprim; Vancomycin

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

Following the discovery of Legionella pneumophila as the cause of an epidemic of pneumonia at an American Legion Convention in Philadelphia, a group of related bacteria were recognized as additional human pathogens. This newly established bacteria genus, Legionella, includes the agents of Legionnaires' Disease, Pittsburgh pneumonia and several related infections. A number of researches have been performed in the past few years about these bacteria; many of these data are here summarized to give an idea of the most important characteristics of Legionella and of the diseases they cause.

Topics: Antibody Formation; Bacterial Infections; Disease Outbreaks; Erythromycin; Humans; Legionella; Legionnaires' Disease; Phenotype; Pneumonia; Postoperative Complications; Rifampin; Serotyping; Tetracycline

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Bacterial Infections; Cattle; Cattle Diseases; Chloramphenicol; Erythromycin; Female; Horse Diseases; Horses; Kinetics; Oxytetracycline; Penicillins; Respiratory Tract Infections; Rifampin

Topics: Bacteria; Bacterial Infections; Humans; Kinetics; Meningitis; Rifampin

A review of the published literature has allowed the identification of a number of non-tubercular indications where rifampicin (trade mark Ciba-Geigy: Rimactane) has been successfully used in combination with other chemotherapeutic agents. The cases reviewed with regard to effectiveness sum 562. The most frequently combined drugs were aminoglycosides (mainly gentamicin), cotrimoxazole, colistine, vancomycin and fusidic acid, these two latter in cases due to Staphylococcus spp. The main indications where combined rifampicin treatment led to favourable results were UTI (success rate 64.9%), bone infections (86.9%), staphylococcal endocarditis (85.0%), respiratory tract infections often due to gram-negative rods (97.7%) as well as skin and soft tissue infections (83.3%), and bacterial meningitis (100%). Very favourable results were obtained in a non-life-threatening though epidemiologically important condition, i.e. salmonella carriers, where a 100% conversion rate was reached in an average period of 6 weeks. Special attention may deserve the combined treatment of fungal infections with rifampicin and amphotericin B. Tolerability was evaluated on a total of 650 cases. It appears to be good for daily doses up to 1,200 mg/day, even on long-term treatment; less so for the highest doses used (1,800 or 30 mg/kg a day). The clinical results, which are in good agreement with the results of the in vitro tests, indicate that rifampicin may have an important role in the combined treatment of severe non-mycobacterial infections. Further prospective, whenever possible, comparative studies are warranted for a thorough appraisal of its possible usefulness.

Topics: Anti-Infective Agents; Bacterial Infections; Drug Combinations; Humans; Mycoses; Rifampin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacitracin; Bacterial Infections; Cephalosporins; Child; Child, Preschool; Chloramphenicol; Clindamycin; Drug Combinations; Drug Therapy, Combination; Erythromycin; Humans; Infant; Kidney Diseases; Lincomycin; Nalidixic Acid; Nitrofurans; Oxolinic Acid; Penicillin Resistance; Penicillins; Polymyxins; Rifampin; Sulfamethoxazole; Sulfonamides; Tetracyclines; Trimethoprim; Vancomycin

Topics: Ampicillin; Bacterial Infections; Brain Edema; Child, Preschool; Chloramphenicol; Cloxacillin; Gentamicins; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Injections, Spinal; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Methicillin; Minocycline; Neisseria meningitidis; Penicillin G; Rifampin; Seizures; Shock; Streptococcus pneumoniae; Sulfonamides

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloglycin; Clindamycin; Doxycycline; Gentamicins; Humans; Imidazoles; Indenes; Minocycline; Penicillin Resistance; Penicillins; Rifampin; Spectinomycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Cephalosporins; Clindamycin; Dosage Forms; Gentamicins; Humans; Lincomycin; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin

Topics: Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Chloramphenicol; Drug Combinations; Erythromycin; Humans; Penicillin Resistance; Penicillins; Rifampin; Ristocetin; Tetracycline; Vancomycin

Topics: Animals; Antibiotics, Antineoplastic; Antitubercular Agents; Antiviral Agents; Bacteria; Bacterial Infections; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; DNA-Directed RNA Polymerases; Drug Resistance, Microbial; Humans; Leprosy; Microbial Sensitivity Tests; Rifampin; Tuberculosis

Topics: Animals; Bacteria; Bacterial Infections; Bile; Carbon Isotopes; Chemical Phenomena; Chemistry; Child, Preschool; Drug Combinations; Drug Interactions; Drug Resistance, Microbial; Female; Fetus; Guinea Pigs; Humans; In Vitro Techniques; Mice; Microbial Sensitivity Tests; Pregnancy; Pregnancy Complications, Infectious; Protein Binding; Rabbits; Rifampin; Time Factors; Viruses

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Resistance, Microbial; Endocarditis, Bacterial; Gonorrhea; Humans; Intestinal Absorption; Leprosy; Meningococcal Infections; Mycobacterium; Respiratory Tract Infections; Rifampin; Thrombocytosis; Tuberculosis; Tuberculosis, Pulmonary; Urologic Diseases; Viruses

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

Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections.. We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months.. A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98).. Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Defibrillators, Implantable; Female; Heart Diseases; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Minocycline; Pacemaker, Artificial; Prosthesis-Related Infections; Rifampin; Single-Blind Method; Standard of Care

 Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described..  In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively..  Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected..  The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research..  NCT01756924.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Interactions; Drug Therapy, Combination; Female; Fusidic Acid; Humans; Male; Middle Aged; Prosthesis-Related Infections; Rifampin

Antimicrobial central venous catheters are discussed as a device to reduce catheter-related infections. Previously we have reported a study with 223 adult surgical patients randomized to receive either a rifampicin-miconazole-loaded central venous catheter (CVC) (n=118) or a standard CVC (n=105). The antimicrobial CVC was shown to reduce catheter colonization (CC) and catheter-related local infection (CRI) significantly even at long-term catheterization. Here, we present further evaluation of the study focusing on possible benefits for high-risk patients. Subgroup analyses showed a pronounced reduction of CC and CRI in male, overweight and oncology patients. Important covariates were skin colonization for CC and oncological disease for CRI. Odds ratio (OR) for reducing CC was 0.076 (95% CI: 0.016-0.360) and CRI was reduced from 26% to 2.3% (p=0.001) in the cancer subgroup. Ex vivo long-term antimicrobial activity of modified catheters exceeded 4 weeks.. Immunocompromized patients suffering from cancer, transplantation, and dialysis patients with a long-term vascular access may mostly benefit from rifampicin-miconazole-releasing catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Antifungal Agents; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Coated Materials, Biocompatible; Equipment Contamination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Rifampin; Risk Factors; Young Adult

To determine the efficacy of minocycline and rifampin-impregnated catheters compared to non-impregnated catheters in critically ill patients.. Prospective, randomized, double-blind, controlled, multicenter trial.. Intensive care units of seven acute-care teaching hospitals in Spain. PATIENTS. Intensive care unit patients requiring triple-lumen central venous catheter for more than 3 days.. At catheter insertion, 228 patients were randomized to minocycline and rifampin-impregnated catheters and 237 to non-impregnated catheters. Skin, catheter tip, subcutaneous segment, hub cultures, peripheral blood and infusate cultures were performed at catheter withdrawal. The rate of colonization, catheter-related bloodstream infection (CRBSI) and catheter-related clinical infectious complications (purulence at the insertion site or CRBSI) were assessed.. In the intention-to-treat analysis (primary analysis), the episodes per 1000 catheter days of clinical infectious complications decreased from 8.6 to 5.7 (RR =0.67, 95% CI 0.31-1.44), CRBSI from 5.9 to 3.1 (RR =0.53, 95% CI 0.2-1.44) and tip colonization from 24 to 10.4 (RR =0.43, 95% CI 0.26-0.73). Antimicrobial-impregnated catheters were associated with a significant decrease of coagulase-negative staphylococci colonization (RR =0.24, 95% CI 0.13-0.45) and a significant increase of Candida spp. colonization (RR =5.84, 95% CI 1.31-26.1).. The use of antimicrobial-impregnated catheters was associated with a significantly lower rate of coagulase-negative staphylococci colonization and a significant increase in Candida spp. colonization, although a decrease in CRBSI, increase in 30-day survival or reduced length of stay was not observed.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood-Borne Pathogens; Catheterization, Central Venous; Catheters, Indwelling; Critical Illness; Cross Infection; Double-Blind Method; Drug Delivery Systems; Humans; Intensive Care Units; Minocycline; Prospective Studies; Rifampin; Treatment Outcome

Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections.. Prospective controlled non-blinded randomized clinical trial in two German university hospitals.. 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable.. Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection.. A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed.. CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Equipment Contamination; Female; Humans; Male; Miconazole; Middle Aged; Mycoses; Prospective Studies; Rifampin; Sepsis; Treatment Outcome

Catheter-related infection of the cerebrospinal fluid (CSF) pathways is a potentially life-threatening complication of external ventricular drainage. A major source of infection is bacterial contamination along the external ventricular drain (EVD) catheter track. The authors examined the efficacy of EVD catheters impregnated with minocycline and rifampin in preventing these catheter-related infections.. The authors conducted a prospective, randomized clinical trial at six academic medical centers. All hospitalized patients 18 years or older who required placement of an EVD catheter were eligible for inclusion in the study. Patients were randomly assigned to undergo placement of an EVD with a catheter impregnated with minocycline and rifampin or a standard untreated catheter (control group). To assess primary outcome, CSF samples were collected using a sterile technique at the time of catheter insertion, at least every 72 hours while the catheter remained in place, and at the time of catheter removal. At the time of removal, CSF cultures were obtained from the tip and tunneled segments of each catheter by performing semiquantitative roll-plate and quantitative sonication techniques. Of the 306 patients enrolled in the study, data from 288 were included in the final analysis. Eighteen patients were excluded from analysis: 14 because the ventricular catheter was in place less than 24 hours, and four because CSF cultures obtained at the time of catheter insertion were positive for infection. Of these 288 patients, 139 were assigned to the control group and 149 to the treatment group. The two groups were well matched with respect to all clinical characteristics, including patient sex and mean age, indication for catheter placement, and length of time the catheter remained in place. The antibiotic-impregnated catheters were one half as likely to become colonized as the control catheters (17.9 compared with 36.7%, respectively, p < 0.0012). Positive CSF cultures were seven times less frequent in patients with antibiotic-impregnated catheters compared with those in the control group (1.3 compared with 9.4%, respectively, p = 0.002).. The use of EVD catheters impregnated with minocycline and rifampin can significantly reduce the risk of catheter-related infections.

Topics: Anti-Infective Agents, Local; Bacterial Infections; Brain Injuries; Catheters, Indwelling; Cerebral Ventricles; Humans; Intracranial Hypertension; Minocycline; Prospective Studies; Rifampin

The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter-related infection in melanoma patients treated with interleukin-2 (IL-2) plus interferon-alpha and chemotherapy (biochemotherapy).. Patients with advanced melanoma who were treated with biochemotherapy at the University of Texas M. D. Anderson Cancer Center were randomized in a crossover study to receive either oral antibiotic prophylaxis consisting of novobiocin and rifampin or observation alone over a 35-day course period. Patients were subsequently "crossed over" to the opposite arm of the study for an additional 35-day period, with each serving as his or her own control.. Twenty-six patients were enrolled. Nine patients (35%) failed to tolerate oral antibiotics because of severe nausea and vomiting; 17 patients (65%) were crossed over and considered evaluable. During the control patient courses, 71% of evaluable patients had infectious complications, 41% had a catheter-associated bacteremia, and 53% had a local catheter infection. In contrast, of the patients treated with antibiotic prophylaxis, only 12% had an infectious complication (P = 0.001), 12% had a local catheter infection (P = 0.008), and 6% had catheter-associated bacteremias (P = 0.04). Thirty-six episodes of catheter infections occurred during the 17 control courses, whereas only 3 episodes occurred during antibiotic prophylaxis (P < 0.001).. Although more than one-third of patients receiving IL-2 treatment with biochemotherapy failed to tolerate novobiocin and rifampin, this oral antibiotic regimen was efficacious in preventing the infectious complications, especially those associated with vascular catheters, in this high risk patient population.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Infections; Catheterization, Central Venous; Catheterization, Peripheral; Catheters, Indwelling; Chemoprevention; Cross-Over Studies; Equipment Contamination; Female; Humans; Immunologic Factors; Interferon-gamma; Interleukin-2; Male; Melanoma; Middle Aged; Nausea; Novobiocin; Prospective Studies; Rifampin; Vomiting

To develop diagnostic and treatment strategies for peritoneal dialysis catheter exit-site and tunnel infections.. All consenting peritoneal dialysis patients performing home dialysis through the University of Iowa Hospitals and Clinics Home Dialysis Training Center. This is a state-owned teaching hospital serving a rural population of approximately one million people in Iowa and western Illinois.. Four dialysis nurses collected information on a prospectively designed data acquisition tool. Patients were randomly assigned to one of two treatment groups, intraperitoneal vancomycin plus oral rifampin or oral trimethoprim/sulfamethoxazole (TMP/SMX), and their initial antibiotic therapy determined by that assignment. If the infection was gram-negative, the initial antibiotics were discontinued and an alternative therapy begun. Therapy was initiated by the nursing staff and required physician notification within 48 hours.. There were 126 recorded catheter infections (exit-site, tunnel, or cuff infection) resulting in a rate of 0.67 episodes per patient year of exposure. Staphylococcus aureus was isolated from the majority (60%) of these events. Pseudomonas aeruginosa was the next most common isolate and accounted for 21% of infections. Rubor, dolor, and turgor are the classic signs of inflammation, and at least one of these was present in 79% of the episodes. Isolated pericatheter erythema or serous discharge was associated with a minimal risk (< 2%) of catheter loss. The presence of a purulent exit-site discharge identified patients who had a 30% chance of failing systemic antibiotic therapy and a 20% risk of catheter loss. The concurrent presence of exit-site tenderness or swelling identified the most severe infections. Staphylococcal infections responded equally well to local cleaning and vancomycin plus rifampin (86% cured) or oral trimethoprim/sulfamethoxazole (89% cured) therapy. Gram-negative infections were frequent (27%) and appeared to respond best to a combination of tobramycin and ciprofloxacin.. Exit-site/tunnel inflammation is detectable by patients and can be used to guide therapy. An isolated finding of erythema or serous discharge is not indicative of an acute infection and may not require systemic antibiotics. The presence of purulence identifies patients at risk for catheter loss, and these patients benefit from systemic therapy. The combination of a purulent exit-site discharge plus pericatheter tenderness or swelling identifies patients likely to suffer treatment failure and require subsequent catheter removal. The cure rate of gram-positive catheter infections treated with vancomycin plus rifampin was indistinguishable from that achieved with oral trimethoprim/sulfamethoxazole (p = 0.99).

Topics: Bacterial Infections; Catheterization; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

We studied the effectiveness of prophylactic oral ciprofloxacin and rifampin on fever prevention in patients undergoing autologous bone marrow transplantation (ABMT) for breast cancer. Furthermore, we evaluated the toxicity and efficacy of empiric once-daily vancomycin and tobramycin for febrile neutropenia.. Ninety-nine assessable women received prophylactic ciprofloxacin and rifampin after high-dose chemotherapy (HDC) for advanced or high-risk primary breast cancer supported with either bone marrow and peripheral-blood progenitor cells (PBPCs) or bone marrow purged with chemotherapy and monoclonal antibodies. Neutropenic fever was treated with empiric once-daily vancomycin and tobramycin. Patients were compared with historic controls treated with the identical HDC and bone marrow support regimen.. In patients treated with bone marrow and PBPCs, the incidence of fever during neutropenia was reduced by ciprofloxacin and rifampin from 98% to 57%. Documented infections were reduced from 42% to 13% (P < .01) and bacteremia from 18% to 0% (P < .001). In purged bone marrow recipients, the overall infection rate decreased from 74% to 17% (P < .001), and bacteremia from 29% to 7%. (P = .02). No patient developed breakthrough bacteremia or sepsis syndrome while on study. Serum creatinine level greater than 1.8 g/dL was noted in 7% of controls and 10% of study patients. Increased ototoxicity was not encountered with the higher peak concentrations of vancomycin and tobramycin.. The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients. Once-daily vancomycin and tobramycin was safe and effective and, because of the ease of use, facilitates outpatient management of ABMT patients.

Topics: Administration, Oral; Adult; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Bone Marrow Purging; Bone Marrow Transplantation; Breast Neoplasms; Ciprofloxacin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Injections, Intravenous; Middle Aged; Neutropenia; Rifampin; Stem Cell Transplantation; Tobramycin; Vancomycin

Acedapsone (DADDS), a repository sulfone given by injection five times a year, has been used since 1967 for the treatment of all leprosy patients in the Karimui, an area of diffic-lt access. More than 460 patients have been treated, 336 beginning in November 1967 and continuing through the latest assessment 6 years later. The injections have been well received and they have been administered very regularly. Clinical observations were begun before 1967, as a base-line of assessments was available for the patients whose disease appeared before that time. The response to DADDS therapy has been satisfactory except in 5 of the 28 multibacillary patients in whose smears solid-staining Mycobacterium leprae have reappeared. M. leprae was isolated in mice from three of these patients; one strain has been proven to be completely susceptible to dapsone (DDS), and the other two very probably are. DDS levels in the plasma of these five patients were normal and well above the minimal inhibitory concentration. The most probable explanation is that a few viable M. leprae survived in the presence of inhibitory concentrations of DDS for the 4 to 6 years during which dead bacilli were disintegrating and disappearing from the tissues. The other 23 multibacillary patients responded satisfactorily. The decrease in the number of M. leprae in the skin smears has been most prompt in patients with low initial bacterial loads and in those with borderline lepromatous diagnoses. A high initial bacterial load and a fully lepromatous diagnosis were associated with a slow initial loss of M. leprae in the 1st year, followed by a more rapid loss the next year. All of the multibacillary patients have now been treated by the addition of a 90-day course of rifampicin.

Topics: Acetamides; Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Dapsone; Dosage Forms; Female; Humans; Infant; Leprostatic Agents; Leprosy; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium leprae; New Guinea; Recurrence; Remission, Spontaneous; Rifampin; Time Factors

In recent years, traditional antibiotic efficacy has rapidly diminished due to the advent of multidrug-resistant (MDR) bacteria, which poses severe threat to human life and globalized healthcare. Currently, the development cycle of new antibiotics cannot match the ongoing MDR infection crisis. Therefore, novel strategies are required to resensitize MDR bacteria to existing antibiotics. In this study, novel cationic polysaccharide conjugates Dextran-graft-poly(5-(1,2-dithiolan-3-yl)-N-(2-guanidinoethyl)pentanamide) (Dex-g-PSS

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Dextrans; Disulfides; Humans; Mice; Microbial Sensitivity Tests; Rifampin

Arr is an ADP-ribosyltransferase enzyme primarily reported in association with rifamycin resistance, which has been used to treat tuberculosis in addition to Gram-positive infections and, recently, pan-resistant Gram-negative bacteria. The arr gene was initially identified on the Mycolicibacterium smegmatis chromosome and later on Proteobacteria plasmids. This scenario raised concerns on the distribution and spread of arr, considering the Bacteria domain. Based on 198,082 bacterial genomes/metagenomes, we performed in silico analysis, including phylogenetic reconstruction of Arr in different genomic contexts. Besides, new arr alleles were evaluated by in vitro analysis to assess their association with rifampin resistance phenotype. The arr gene was prevalent in thousands of chromosomes and in hundreds of plasmids from environmental and clinical bacteria, mainly from the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. Furthermore, this gene was identified in other and new genomic contexts. Interestingly, Arr sequences associated with rifampin resistance were distributed across all phylogeny, indicating that, despite the diversity, their association with rifampin resistance phenotype were maintained. In fact, we found that the key residues were highly conserved. In addition, other analyzes have raised evidence of another Arr function, which is related to guanidine metabolism. Finally, this scenario as a whole also suggested the Actinobacteria phylum as a potential ancestral source of arr within the Bacteria domain.

Topics: ADP Ribose Transferases; Amino Acid Sequence; Bacteria; Bacterial Infections; Base Composition; Base Sequence; Conserved Sequence; Drug Resistance, Bacterial; Genome, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Phylogeny; Rifampin

An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration.. Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route.. The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Bacterial Infections; Bone Diseases; Clindamycin; Female; Humans; Joint Diseases; Male; Middle Aged; Prospective Studies; Rifampin

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

Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO.. We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria.. In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively).. Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Ciprofloxacin; Clindamycin; Drug Therapy, Combination; Empirical Research; Enterobacteriaceae; Female; Gene Expression; Humans; Levofloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Osteomyelitis; Retrospective Studies; Rifampin; Spine; Streptococcus; Vancomycin

External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain.. Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS.. Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1 week or 4 weeks, and examined for evidence of inflammation and toxicity.. Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4 week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity.. The antimicrobial catheter appears to withstand bacterial challenge for at least 4 weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Catheter-Related Infections; Catheterization; Catheters; Cerebral Ventriculitis; Cerebrospinal Fluid Leak; Disease Models, Animal; Humans; Male; Models, Theoretical; Rats, Wistar; Rifampin; Treatment Outcome; Triclosan; Trimethoprim

Complex extremity wounds in Wounded Warriors can become contaminated with microbes, which may cause clinical outcomes resulting in amputation, morbidity, or even fatality. Local delivery of multiple or broad-spectrum antibiotics allows practicing clinicians treatment solutions that may inhibit biofilm formation. Propagation of vancomycin-resistant Staphylococcus aureus is also a growing concern. The development of vancomycin-resistant S. aureus has become a critical challenge in nosocomial infection prevention in the USA, but to date has seen little occurrence in osteomyelitis. As an alternative, locally delivered ciprofloxacin and rifampin were investigated in a preclinical model for the prevention of biofilm in complex extremity wounds with implanted fixation device. In vitro assays demonstrated ciprofloxacin and rifampin possess an additive effect against Gram-negative Pseudomonas aeruginosa and were actively eluted from a chitosan sponge based local delivery system. In an in vivo orthopedic hardware-associated polymicrobial model (S. aureus and Escherichia coli) the combination was able to achieve complete clearance of both bacterial strains. E. coli was detected in bone of untreated animals, but did not form biofilm on wires. Results reveal the clinical potential of antibiotic-loaded chitosan sponges to inhibit infection through tailored antibiotic selection at desired concentrations with efficacy towards biofilm inhibition.

Topics: Analysis of Variance; Animals; Anti-Bacterial Agents; Bacterial Infections; Biopolymers; Chitosan; Chromatography, High Pressure Liquid; Ciprofloxacin; Mice; Microbial Sensitivity Tests; Rifampin; Staphylococcus aureus

A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level.

Topics: Anti-Infective Agents; Antimalarials; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Malaria, Falciparum; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Plasmodium falciparum; Pyrazoles; Quinolines; Structure-Activity Relationship; Tuberculosis

The clinical management of prosthetic joint infections and other persistent bacterial infections represents a major unmet medical need. The rifamycins are one of the most potent antibiotic classes against persistent bacterial infections, but bacteria can develop resistance to rifamycins rapidly and the clinical utility of the rifamycin class is typically limited to antibiotic combinations to minimize the development of resistance. To develop a better therapy against persistent bacterial infections, a series of rifamycin based bifunctional molecules were designed, synthesized, and evaluated with the goal to identify a dual-acting drug that maintains the potent activity of rifamycins against persistent pathogens and at the same time minimize the development of rifamycin resistance. TNP-2092 was identified as a drug candidate and is currently in an early stage of clinical development for the treatment of prosthetic joint infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Microbial Sensitivity Tests; Molecular Structure; Rifamycins; Staphylococcus aureus; Structure-Activity Relationship

The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated.. Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria.. Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria.. These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteria; Bacterial Infections; beta-Cyclodextrins; Ciprofloxacin; Click Chemistry; Drug Carriers; Drug Resistance, Bacterial; Erythromycin; Glucose; Humans; Mannose; Microbial Sensitivity Tests; Rifampin; Staphylococcus aureus

In this paper we report the SAR studies of a series of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)amide and N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)sulfonamide derivatives 6(a-o) and 7(a-o), were synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The preparation of the key intermediate highlights an optimized palladium catalyzed (Pd₂(dba)₃/RuPhos) Buchwald cross-coupling of intermediate 2 and 3. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7d, 7f, 7h and 7n displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Topics: Amides; Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Structure-Activity Relationship; Sulfonamides

Implant-associated infections following invasive orthopedic surgery are a major clinical problem, and are one of the primary causes of joint failure following total joint arthroplasty. Current strategies using perioperative antibiotics have been met with little clinical success and have resulted in various systemic toxicities and the promotion of antibiotic resistant microorganisms. Here we report the development of a biodegradable localized delivery system using poly(D,L-lactic acid-co-glycolic acid) (PLGA) for the combinatorial release of fusidic acid (FA) (or its sodium salt; SF) and rifampicin (RIF) using electrospinning. The drug-loaded formulations showed good antibiotic encapsulation (~75%-100%), and a biphasic drug release profile. All dual-loaded formulations showed direct antimicrobial activity in vitro against Staphylococcus epidermidis, and two strains of methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, lead formulations containing 10% (w/w) FA/SF and 5% (w/w) RIF were able to prevent the adherence of MRSA to a titanium implant in an in vivo rodent model of subcutaneous implant-associated infection.

Topics: Animals; Anti-Bacterial Agents; Arthroplasty, Replacement; Bacterial Infections; Drug Delivery Systems; Female; Fusidic Acid; Lactic Acid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nanofibers; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostheses and Implants; Prosthesis-Related Infections; Rats; Rats, Sprague-Dawley; Rifampin; Staphylococcus epidermidis

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Humans; Male; Minocycline; Penile Prosthesis; Postoperative Complications; Rifampin

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Humans; Male; Minocycline; Penile Prosthesis; Postoperative Complications; Rifampin

A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by (1)H NMR, (13)C NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffraction study. The compounds were evaluated for their preliminary in vitro antibacterial, antifungal activity and were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The synthesized compounds displayed interesting antimicrobial activity.

Topics: Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Crystallography, X-Ray; Fungi; Humans; Microbial Sensitivity Tests; Models, Molecular; Mycobacterium tuberculosis; Mycoses; Thiazoles; Tuberculosis

Prolonged treatment with linezolid may cause toxicity. The purpose of this study was to define pharmacodynamic thresholds for improving safety outcomes of linezolid.. We performed a retrospective study of patients who had trough (C(min)) and peak (C(max)) plasma levels measured during prolonged linezolid treatment. Dosage adjustments were performed when C(min) ≥10 mg/L and/or AUC₂₄ ≥400 mg/L · h. Patients were divided into two subgroups according to the absence or presence of co-treatment with rifampicin (the linezolid group and the linezolid + rifampicin group, respectively). Data on demographic characteristics, disease, microbiology and haematochemical parameters were collected and outcomes in relation to drug exposure were compared between groups.. A total of 45 patients were included. Dosage adjustments were needed in 40% versus 0% of patients in the linezolid group (n = 35) versus the linezolid + rifampicin group (n = 10), respectively. Patients in the linezolid group had either significantly higher C(min) [3.71 mg/L (1.43-6.38) versus 1.37 mg/L (0.67-2.55), P < 0.001] or AUC₂₄ [212.77 mg/L · h (166.67-278.42) versus 123.33 mg/L · h (97.36-187.94), P < 0.001]. Thrombocytopenia appeared in 51.4% versus 0% of cases in the linezolid group versus the linezolid + rifampicin group, respectively. In 33.3% of those patients who were experiencing thrombocytopenia, therapeutic drug monitoring (TDM)-guided dosage reductions allowed recovery from toxicity and prosecution of therapy with good outcome. A logistic regression model for thrombocytopenia estimated a probability of 50% in the presence of C(min) of 6.53 mg/L and/or of AUC₂₄ of 280.74 mg/L · h.. Maintenance over time of C(min) between 2 and 7 mg/L and/or of AUC₂₄ between 160 and 300 mg/L · h may be helpful in improving safety outcomes while retaining appropriate efficacy in adult patients receiving prolonged linezolid treatment.

Topics: Acetamides; Adult; Anti-Bacterial Agents; Bacterial Infections; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Plasma; Retrospective Studies; Rifampin; Treatment Outcome

Medical and pharmacological communities have long searched for antimicrobial drugs that increase their effect when used in combination, an interaction known as synergism. These drug combinations, however, impose selective pressures in favour of multi-drug resistance and as a result, the benefit of synergy may be lost after only a few bacterial generations. Furthermore, there is experimental evidence that antibiotic treatment can disrupt colonization resistance by shifting the balance between enteropathogenic and commensal bacteria in favour of the pathogens, with the potential to increase the risk of infections. So, we ask, what is the best way of using synergistic drugs? We pose an evolutionary model of commensal and pathogenic bacteria competing in a continuous culture device for a single limiting carbon source under the effect of two bacteriostatic and synergistic antibiotics. This model allows us to evaluate the efficacy of different drug deployment strategies and, using ideas from optimal control theory, to understand whether there are circumstances in which other types of therapy might be favoured over those based on fixed-dose multi-drug combinations. Our main result can be stated thus: the optimal deployment of synergistic antibiotics to remove a pathogen in the presence of commensal bacteria in our model system occurs not in combination, but by deploying them sequentially.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bioreactors; Drug Resistance, Multiple; Drug Synergism; Humans; Models, Biological; Rifampin

Patients who undergo device revision surgery are at higher risk for infection than virgin implant recipients. The revision rate due to virgin implant infection is statistically significantly lower for minocycline/rifampin impregnated than for nonimpregnated inflatable penile prostheses. We determined whether the frequency of infection revision events after device replacement surgery would also be lower for minocycline/rifampin impregnated inflatable penile prostheses.. Patient information forms voluntarily submitted to AMS® after replacement inflatable penile prosthesis implantation between 2001 and 2007 were retrospectively reviewed to compare secondary infection related revision events for antibiotic impregnated vs nonimpregnated implants. Only men who received an inflatable penile prosthesis at a first recorded operation to replace a previously implanted penile prosthesis were included in the study. Life table survival analysis was done between the groups to compare infection related events resulting in a second surgical revision after replacement implantation. Survival function extrapolation was based on parametric analysis using the Weibull distribution model.. On life table survival analysis secondary revision due to infection was significantly less common in the minocycline/rifampin impregnated group than in the nonimpregnated group (log rank p = 0.0252). At up to 6.6 years of followup 2.5% of 9,300 men with vs 3.7% of 1,764 without an impregnated device underwent secondary revision due to infection.. This long-term device survival analysis provides clinical evidence of a significant decrease in infection related secondary revisions using minocycline/rifampin impregnated prostheses vs nonimpregnated inflatable penile prostheses at replacement implant surgery.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Penile Prosthesis; Postoperative Complications; Prosthesis Design; Reoperation; Retrospective Studies; Rifampin; Time Factors; Treatment Outcome

We describe a septic loosening of a hip prosthesis in a 71-year-old woman caused by Gardnerella vaginalis. Infection was confirmed by culture and molecular identification of this bacterium. The patient was treated by a one-step exchange of prosthesis and antibiotic therapy combining trimethoprim-sulfamethoxazole and rifampin, with favorable evolution.

Topics: Aged; Anti-Bacterial Agents; Arthritis; Arthroplasty, Replacement, Hip; Bacterial Infections; Female; Gardnerella vaginalis; Humans; Molecular Sequence Data; Prosthesis-Related Infections; Rifampin; Sequence Analysis, DNA; Trimethoprim, Sulfamethoxazole Drug Combination

For long-term orthopaedic implants, the creation of a surface that is repulsive to bacteria while adhesive to tissue cells represents a promising strategy to control infection. To obtain such multifunctional surfaces, two possible approaches were explored to incorporate a model antibiotic, rifampicin (Rf), into the osteogenic polycaprolactone (PCL)/chitosan (CHS) biomimetic nanofibre meshes by (1) blending Rf into the electrospinning solutions and then electrospinning into nanofibres (i.e., Rf-incorporating fibres), or (2) depositing Rf-containing poly(D,L-lactic-co-glycolic) acid (PLGA) micro-patterns onto the PCL/chitosan nanofibre meshes via ink-jet printing (i.e., Rf-eluting micro-pattern/fibre). Rapid release of Rf from both meshes was measured even though a relatively slower release rate was obtained from the Rf-eluting micro-pattern ones. Antibacterial assay with Staphylococcus epidermidis showed that both mesh surfaces could effectively kill bacteria and prevent biofilm formation. However, only Rf-eluting micro-pattern meshes favoured the attachment, spreading and metabolic activity of preosteoblasts in the cell culture study. Furthermore, the Rf-eluting micro-pattern meshes could better support the osteogenic differentiation of preosteoblasts by up-regulating the gene expression of bone markers (type I collagen and alkaline phosphatase). Clearly, compared to Rf-incorporating nanofibre meshes, Rf-eluting micro-patterns could effectively prevent biofilm formation without sacrificing the osteogenic properties of PCL/chitosan nanofibre surfaces. This finding provides an innovative avenue to design multifunctional surfaces for enhancing bone tissue formation while controlling infection.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Infections; Biofilms; Biomimetic Materials; Cell Differentiation; Cells, Cultured; Chitosan; Mice; Nanofibers; Osteoblasts; Osteogenesis; Polyesters; Rifampin; Staphylococcus epidermidis

Infection is the worst complication seen with inflatable penile prosthesis (IPP). Both the American Medical Systems (AMS) and Coloplast IPP have infection retardant coatings. AMS is coated at the factory with rifampicin and minocycline (InhibiZone). The Coloplast IPP has a hydrophilic coating covalently bonded to its components that will absorb any aqueous solution before implantation and provides increased surface lubricity to decrease bacterial adherence.. We tested several antibiotic dips comparing zones of inhibition (ZOI) against five commonly infecting bacteria with coated Coloplast implants. Results were compared with those ZOI created with strips of an AMS IPP precoated with InhibiZone..   Pieces of sterile Coloplast Titan IPP were dipped in (i) trimethoprim/polymixin B ophthalmic solution; (ii) trimethoprim/sulfamethoxazole infusion solution; (iii) bacitracin; (iv) rifampicin/minocycline; and (v) rifampin/trimehtoprim/sulfamethoxazole. ZOI for the Titan strips and for AMS InhibiZone coated strips were tested against Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus aureus, Pseudomonas, and Enterococcus.. ZOIs of the Coloplast Titan for each of the medicated solutions were compared with ZOI created by undipped strips of a sterile InhibiZone coated IPP placed on plates of the identical bacteria.. All dips except bacitracin showed ZOI≥InhibiZone (P≥0.005) for most organisms. Because of broad-spectrum effectiveness, ease of handling, and cost, infusion vial of trimehtoprim/sulfamethoxazole seemed optimal at this time. If trimehtoprim/sulfamethoxazole is unavailable; the ZOI with Polytrim ophthalmic solution zones were almost as good.. The Coloplast strips when dipped in several solutions showed equal or significantly larger ZOI against commonly infecting organisms than the InhibiZone coated strips. At the present time using off the shelf trimethoprim sulfamethoxazole infusion solution seems optimum. The flexibility of choosing the drug eluting from the Coloplast device seems promising in the changing bacterial environment.

Topics: Anti-Bacterial Agents; Bacitracin; Bacterial Infections; Drug Therapy, Combination; Humans; Minocycline; Penile Implantation; Penile Prosthesis; Prosthesis-Related Infections; Rifampin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous vasculitis is a clinical entity with a broad differential diagnosis, including an adverse drug reaction. It is defined as inflammation of skin blood vessel walls. During a 7-year-period, we observed three patients who developed isolated cutaneous vasculitis during antibiotic therapy of bacterial infection. All were treated with a fluoroquinolone (ciprofloxacin or levofloxacin) combined with rifampin (two cases) or flucloxacillin (three cases), respectively. In all three cases the lesions gradually resolved after treatment with the inciting fluoroquinolone had been stopped. In one patient, leukocytoclastic small-vessel vasculitis was histologically confirmed. Fluoroquinolone-associated cutaneous vasculitis consists of an isolated self-limiting disorder that is part of a systemic vasculitis, or even life-threatening disease. Clinicians should be aware of this serious adverse event because any continuation of treatment may be fatal.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Floxacillin; Fluoroquinolones; Humans; Male; Rifampin; Skin Diseases; Vasculitis; Withholding Treatment

QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic compound is an unusual barbituric acid derivative whose activity resides in the (-)-enantiomer. QPT-1 had activity against a broad spectrum of pathogenic, antibiotic-resistant bacteria, was nontoxic to eukaryotic cells, and showed oral efficacy in a murine infection model, all before any medicinal chemistry optimization. Biochemical and genetic characterization showed that the QPT-1 targets the beta subunit of bacterial type II topoisomerases via a mechanism of inhibition distinct from the mechanisms of fluoroquinolones and novobiocin. Given these attributes, this compound represents a promising new class of antibacterial agents. The success of this reverse genomics effort demonstrates the utility of exploring strategies that are alternatives to target-based screens in antibacterial drug discovery.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Bacteria; Bacterial Infections; Bacterial Proteins; Cell Line; Cell Proliferation; Metabolic Clearance Rate; Mice; Microbial Sensitivity Tests; Molecular Structure; Staphylococcus aureus; Stereoisomerism; Topoisomerase II Inhibitors

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

Bacteria from the exit site of dialysis catheter can grow into microcolonies in biofilm. It has been hypothesized that rifampin-protamine combination may have an effect on the biofilm. In hemodialysis centre a combination of rifampin mixed with protamine is commonly used in some centre in order to prevent catheter related infections in hemodialysis patients. Therefore, a pharmaceutical assessment of the rifampin-protamine mixture is clearly mandatory. The aim of this study is to evaluate the stability and the sterility of the rifampin-protamine solution. Five milliliters of protamine (10 mg) was mixed with 10 mL of Rifampin (600 mg). The solution was kept at -20 degrees C temperature for two weeks and subsequently at 4 degrees C for two additional weeks. Stability and sterility were evaluated the first day and two weeks, three weeks and four weeks after the preparation. Concentration of rifampin in the solution was assessed by HPLC. Protamine concentration was evaluated by the effect of the solution on the heparin activity of a heparinized plasma. The solution was cultured on broth media and mannitol agar plate. Areas under curve of rifampin were similar between the four different evaluations. The effect of the solution on the heparin activity was comparable at the four different evaluations. Our results demonstrate the stability and the compatibility of the solution. However, there was biological interference between broth media and the solution. It was, therefore, impossible to make any conclusion after broth culture. Culture on mannitol agar plate did not show any microbiological growth. Based on this finding, we recommend preparing the rifampin-protamine combination in individual conditioning at the time of the utilization.

Topics: Bacterial Infections; Biofilms; Chromatography, High Pressure Liquid; Heparin; Humans; Peritoneal Dialysis; Pharmaceutical Solutions; Protamines; Renal Dialysis; Rifampin

The best antibiotic regimen for acute prosthetic joint infection, treated without removal of the implant, has not been well-defined. This study describes the use of a protocol based on oral rifampicin combinations to treat 47 cases that were followed prospectively for a 2-year period. The regimen used most commonly was levofloxacin 500 mg/24 h plus rifampicin 600 mg/24 h for a mean duration of 2.7 +/- 1 months. The cure rate was 76.9%, and the only independent risk-factor associated with treatment failure was infection caused by methicillin-resistant Staphylococcus aureus or Enterococcus spp. (OR 17.6, p 0.003). Overall, the results suggested that use of oral antibiotics, including rifampicin, for 2-3 months was a good treatment option.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Bacterial Infections; Debridement; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Levofloxacin; Male; Ofloxacin; Prosthesis-Related Infections; Rifampin; Treatment Outcome

Intravascular devices are widely used for vascular access but are associated with substantial risk of development of devices-related bloodstream infection (DR-BSI), which causes a considerable increase of morbidity and mortality, prolonged hospitalisation and growing medical costs. Since conventional treatment of DR-BSI fails in a significant number of cases, resulting in removal of the device, new approaches are needed to prevent bacterial colonization. In this paper, two antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes exhibiting acidic or basic properties. The influence of the type of antibiotic-polymer interaction on the amount of adsorbed antibiotic and on the release kinetics was studied. It was seen that the antibiotic-polymer affinity increases both with the introduction in the polymer side-chain of functional groups and with the matrix hydrophilicity. The antimicrobial activity of the treated polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of antibiotic adsorbed, on the strength of drug-matrix interaction and on the water swelling of the polymers. The inhibition zone of bacterial growth lasts only a few hours for the amoxi-coated polymers while remains at least for five months for the rifampin-coated ones. The presence of serum proteins decreases by about 30% the inhibition zone diameter of these latest matrices after two months.

Topics: Adsorption; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Colony Count, Microbial; Equipment Contamination; Polyurethanes; Rifampin; Staphylococcus aureus; Staphylococcus epidermidis

Topics: Acetamides; Adult; Bacterial Infections; Drug Resistance, Bacterial; Female; Humans; Linezolid; Oxazolidinones; Prosthesis-Related Infections; Rifampin; Sarcoma, Ewing

We have developed a rapid, continuous method for monitoring the effectiveness of several antibacterial agents in real time, noninvasively, by using a recently described mouse model of chronic biofilm infection (J. L. Kadurugamuwa et al., Infect. Immun. 71:882-890, 2003), which relies on biophotonic imaging of bioluminescent bacteria. To facilitate real-time monitoring of infection, we used a Staphylococcus aureus isolate that was made bioluminescent by inserting a modified lux operon into the bacterial chromosome. This bioluminescent reporter bacterium was used to study the antimicrobial effects of several antibiotics belonging to different molecular families. Treatment with rifampin, tobramycin, and ciprofloxacin was started 7 days after subcutaneous implantation of catheters precolonized with 10(4) CFU of S. aureus. Three different doses of antibiotics were administered twice a day for 4 consecutive days. The number of metabolically active bacteria in untreated mice and the tobramycin- and ciprofloxacin-treated groups remained relatively unchanged over the 4-week observation period, indicating poor efficacies for tobramycin and ciprofloxacin. A rapid dose-dependent decline in metabolic activity in rifampin-treated groups was observed, with almost a 90% reduction after two doses and nearly undetectable levels after three doses. The disappearance of light emission correlated with colony counts. After the final treatment, cell numbers rebounded as a function of concentration in a time-dependent manner. The staphylococci isolated from the catheters of mice treated with rifampin were uniformly resistant to rifampin but retained their in vitro susceptibilities to tobramycin and ciprofloxacin. Since the metabolic activities of viable cells and a postantibiotic effect could be detected directly on the support matrix nondestructively and noninvasively, the methodology is specifically appealing for investigating the effects of antibiotics on biofilms in vivo. Moreover, our study points to the possible use of biophotonic imaging for the detection of the development of resistance to therapeutic agents during treatment of chronic infections in vivo.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Biofilms; Catheterization; Ciprofloxacin; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Monitoring; Luminescent Measurements; Mice; Rifampin; Staphylococcus aureus; Tobramycin

The use of antibiotic coated catheters has been proposed as a means of reducing catheter related sepsis. In this study, an in vitro comparison of bacterial colonisation rates was made between uncoated umbilical venous catheters and catheters coated with rifampicin and minocycline. The following parameters were determined; the direct antimicrobial effect of coated and uncoated catheter segments against a range of organisms associated with line sepsis, the assessment of the decline in antimicrobial activity in coated catheters immersed in plasma and the inhibitory efficacy of the catheters to colonisation over a 28-day period. Minocycline and rifampicin coated umbilical catheters showed a superior inhibitory effect and prevented colonisation with the commoner line-related organisms, when compared with uncoated catheters. The inhibitory effect declined after 14 days in the human plasma. Resistance to colonisation in vitro may not extend beyond 21 days.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Infections; Candida albicans; Candidiasis; Catheters, Indwelling; Colony Count, Microbial; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Minocycline; Rifampin; Time Factors; Umbilical Veins

Seventeen diabetic patients with moderate to mild foot lesions associated with 20 osteomyelitic bones diagnosed by both bone scan and bone biopsy received rifampicin plus ofloxacin for a median duration of 6 months. Cure was defined as disappearance of all signs and symptoms of infection at the end of the treatment and absence of relapse during follow up. At the end of the treatment period, cure was achieved in 15 patients (88.2%) and was maintained in 13 patients (76.5%) at the end of an average post-treatment follow-up of 22 months. No serious drug-related adverse events were recorded.

Topics: Administration, Oral; Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Infections; Chronic Disease; Diabetic Foot; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ofloxacin; Osteomyelitis; Rifampin; Treatment Outcome

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

Oral antibiotic therapy achieves clinical and bacteriological cure of the adult bacterial osteomyelitis associated or not to orthopedic implant.. We carried out a prospective study, with follow-up at 24 months, of patients with adult bacterial osteomyelitis, that were initially treated with parenteral antibiotic therapy for a week, followed with oral antibiotic therapy during 2 to 6 months, depending on the absence or presence or orthopedic implant, respectively.. 37 patients presented 44 episodes of adult bacterial osteomyelitis, 34 of them in presence of orthopedic implant. The most frequent causative microorganism was S. aureus (44%), followed by coagulase-negative Staphylococcus (29%). The oral antibiotic therapy most frequently employed was the combination cotrimoxazole-rifampin, followed by ciprofloxacin-rifampin. The clinical and bacteriologic cure were 85%, 82% in the group with orthopedic implant. 82% required surgical intervention.. The oral antibiotic therapy, preceded by a short parenteral therapy, can get high rates of clinical and bacteriological cure in the adult's bacterial osteomyelitis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antibiotics, Antitubercular; Bacterial Infections; Ciprofloxacin; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Osteomyelitis; Prospective Studies; Rifampin; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The in vitro and in vivo activities of catheters coated with minocycline and rifampin and with chlorhexidine gluconate and silver sulfadiazine were evaluated. When incubated in serum at 37 degrees C, the half-life of the inhibitory activity of catheters coated with minocycline and rifampin was 25 days compared with 3 days for catheters coated with chlorhexidine gluconate and silver sulfadiazine. In a rabbit model, catheters coated with minocycline and rifampin were significantly more efficacious than catheters coated with chlorhexidine and silver sulfadiazine in preventing colonization and infection with Staphylococcus aureus (P < .05). Catheters coated with minocycline and rifampin demonstrated broad-spectrum in vitro inhibitory activity against gram-positive bacteria, gram-negative bacteria, and Candida albicans that was significantly superior to the inhibitory activity of catheters coated with chlorhexidine gluconate and silver sulfadiazine (P < .01). Minocycline and rifampin were also highly efficacious in preventing colonization and infection in vivo.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacterial Adhesion; Bacterial Infections; Candida albicans; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Chlorhexidine; Colony Count, Microbial; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Microbial Sensitivity Tests; Minocycline; Rabbits; Rifampin; Silver Sulfadiazine

For the initial treatment of peritonitis complicating peritoneal dialysis (PD), we use intraperitoneally administered gentamicin (broad spectrum and low costs) and rifampin (intracellular bactericidal activity). In order to assess the efficacy of this treatment, the outcome of 248 suspected episodes of peritonitis (abdominal pain, cloudy effluent, and a leukocyte count over 100/mm3) was evaluated. Of 227 cases with a positive culture of the PD effluent, one bacterial species was cultured in 188 cases (75.8%), more than one in 32 cases (12.9%), and in 7 cases (2.8%) yeasts. In 87.2% of the culture-positive cases, a good clinical response to the initialized antibiotic therapy was found. In 20 cases (8.1%) antibiotic treatment was discontinued within one week because no micro-organisms were cultured. In one case no effluent was cultured. Although in vitro resistance or indifference to both antibiotics was found in 45 cases (19.8%), in only 29 culture-positive cases (12.8%) the clinical condition did not improve on initial therapy. Of the peritonitis episodes in which micro-organisms resistant to both antibiotics were cultured, 23 were Staphylococcus epidermidis, 5 were E. coli, 7 were yeasts, and there were miscellaneous (mostly enteral) bacteria in 10 cases. In the studied period no significant changes were found in the susceptibility of the cultured microorganisms to gentamicin and rifampin. Susceptibility profile per episode, however, showed an increasing resistance against both antibiotics. It is concluded that the combination of gentamicin and rifampin as initial treatment of peritonitis is effective in most (87%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Therapy, Combination; Gentamicins; Humans; Microbial Sensitivity Tests; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Retrospective Studies; Rifampin

Infection due to implanted polymeric devices is a major problem in modern medicine. Microbial colonization of implants in neurosurgery, e.g. cerebrospinal fluid (CSF) shunts is the main reason for their failure, and often results in the consequent removal of the infected implants. In this paper we report on new approaches in the prevention of bacterial infections by incorporation of an antibiotic (rifampicin) into the polymer devices (silicone). Drug release characteristics are investigated, and the physico-chemical mechanism of the delivery is discussed. Measurements of killing kinetics and the bacterial adhesion to the antibiotic-loaded silicone in a static adhesion assay reveal that only the liberation of high antibiotic doses over a period of weeks can prevent the bacterial colonization of the polymeric surface.

Topics: Animals; Bacterial Adhesion; Bacterial Infections; Cerebrospinal Fluid Shunts; Dose-Response Relationship, Drug; Drug Delivery Systems; Equipment Contamination; Kinetics; Materials Testing; Microscopy, Electron, Scanning; Rabbits; Rifampin; Silicones

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 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

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

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

Chronic orbital inflammatory disease (COID) is usually considered non-infectious and idiopathic. Treatment is empirical, palliative, and may not prevent disease progression. COID occurs in isolation or in association with various systemic diseases. Exophthalmos may be an important presenting sign. Vasculitis, lymphoid infiltrates, and granulomas are common. Mollicute-like organisms (MLO) parasitising and destroying vitreous leucocytes are often found to cause human chronic uveitis when an appropriate search is made. Inoculation of these MLO into mouse eyelids produced chronic uveitis and exophthalmic orbital inflammatory disease. Mollicutes are cell wall deficient bacteria. Extracellular mollicutes cause human and animal diseases characterised by lymphoid infiltrates, immunosuppression, and autoantibody production. Intracellular morphologically similar bacteria are non-cultivable pathogens termed MLO. Identification is based on direct detection in diseased cells by transmission electron microscopy. MLO are cytopathogenic and detection is aided by the alterations they produce. MLO replace the cytoplasm, destroy the organelles, and alter the nucleus. This results in cell proliferation, destruction, and dysfunction. MLO parasitise lymphocytes, monocytes, and polymorphonuclear leucocytes. This report describes orbital leucocytes parasitised by MLO in three patients with isolated COID. Rifampicin treatment of MLO disease is discussed.

Topics: Adolescent; Aged; Bacterial Infections; Chronic Disease; Female; Humans; Inflammation; Leukocytes; Microscopy, Electron; Middle Aged; Mycoplasmatales Infections; Orbital Diseases; Rifampin

In 1986, an outbreak of Moraxella follicular conjunctivitis occurred in girls attending a Navajo boarding school in New Mexico. We diagnosed 19 cases of culture-proven, and 21 of clinical conjunctivitis based on isolation of Moraxella from conjunctival cultures and the occurrence of symptoms significantly associated with positive culture. Sharing eye makeup was significantly associated with Moraxella-positive conjunctivitis (odds ratio [OR] = 7.2, P = .004) and showed a trend toward significance in those with clinical conjunctivitis (OR = 2.9, P = .09). Eyeliner and eye shadow were implicated (OR = 4.1, P less than .05). We cultured samples of 13 students' makeup; one third of the eyeliners were positive for Moraxella. Nasal carriage of Moraxella was found in 35 (44%) of the 79 female boarders and in 20 (21%) of 97 Navajo patients at two nearby clinics. In a prospective evaluation of the effect of patient education and rifampin therapy on the occurrence of conjunctivitis during an 11-month follow-up period, both types of intervention were successful in significantly reducing the rate of conjunctivitis when compared with that in a control group.

Topics: Adolescent; Bacterial Infections; Conjunctiva; Conjunctivitis, Bacterial; Cosmetics; Disease Outbreaks; Female; Humans; Indians, North American; Male; Moraxella; New Mexico; Nose; Patient Education as Topic; Prospective Studies; Rifampin; Risk Factors

The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bacterial Infections; Biological Availability; Female; Horse Diseases; Horses; Microbial Sensitivity Tests; Rifampin

Clinical efficacy of rifampicin, a semisynthetic broad spectrum antibiotic was estimated in 247 patients with purulent inflammations. It was shown advisable to use rifampicin intravenously in treatment of severe bronchopulmonary pathology, disorders of the bile excretion system, osteomyelitis, severe wound infections and in prophylaxis of postoperative purulent complications in cardiovascular surgery and other cases. High rifampicin sensitivity of staphylococci and streptococci belonging to various species was revealed. Rifampicin was found to be less active against gramnegative pathogens. The isolation frequency of rifampicin sensitive strains of E. coli, Proteus spp., Klebsiella spp. and P. aeruginosa amounted to 88.4, 52.1, 58.8 and 49.3 per cent respectively.

Topics: Bacteria; Bacterial Infections; Cholangitis; Drug Resistance, Microbial; Hepatitis; Humans; Osteomyelitis; Respiratory Tract Infections; Rifampin; Wound Infection

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Humans; Meningitis, Haemophilus; Meningitis, Meningococcal; Premedication; Rifampin

Topics: Bacteria, Anaerobic; Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penile Diseases; Rifampin; Ulcer

The effect of recombinant murine interferon-gamma (IFN-gamma) on the growth of Listeria monocytogenes for 4 h and Mycobacterium microti for up to 3 days in monolayers of peritoneal macrophages from BALB/c mice was examined by serial viable counts of cell-associated bacteria. Macrophages pretreated with 10 u IFN-gamma per ml were bacteriostatic and with 100 u or 1000 u per ml were bactericidal against L. monocytogenes. Addition of IFN-gamma 3 days before infection caused monolayers to be bactericidal against M. microti mainly during the first 15 min after infection. This was just evident with 10 u IFN-gamma per ml and greater with 100 u or 1000 u per ml. If IFN-gamma was added when phagocytosis of M. microti was complete, about 2 h after infection, its action was only bacteriostatic, the viable counts remaining stationary while those of unexposed monolayers increased. IFN-gamma 100 u per ml added before infection did not alter the bactericidal activity of rifampicin 10 mg/l, nor did it alter the killing curves for isoniazid 1 mg/l or for rifampicin 10 mg/l if added after completion of phagocytosis.

Topics: Animals; Bacterial Infections; Cells, Cultured; Drug Therapy, Combination; Interferon-gamma; Isoniazid; Listeriosis; Lymphokines; Macrophages; Mice; Mice, Inbred BALB C; Mycobacterium Infections; Recombinant Proteins; Rifampin

It was shown that long-term oral administration of rifampicin (40 mg/kg) to rats was accompanied by a marked decrease in the number of enterococci and staphylococci in their large intestine. A significant decrease in the number of colibacilli and anaerobic nonsporulating gramnegative bacteria was also observed. Discontinuation of the antibiotic administration resulted in rapid recovery of the intestinal flora with respect to all the indices tested. It was found for the first time that pregany of rats with experimental disbacteriosis was characterized by lowered colon resistance in spite of similarity in the intestinal flora of the experimental and control pregany. This was evident from increased periods of indicator microorganism retention in the animal intestine.

Topics: Animals; Animals, Newborn; Bacteria; Bacterial Infections; Feces; Female; Intestinal Diseases; Intestine, Large; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Rifampin; Time Factors

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

Many factors are involved in choice of an antimicrobial agent. Cost has become a matter of increasing concern. Of course, overall expense for the hospitalized patient includes costs of tests for monitoring for toxicity as well as administration costs, which are affected by the dosing frequency. A reasoned choice necessitates knowledge of the place of newer agents in the therapeutic armamentarium and of some new applications of well-established drugs.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cephalosporins; Clindamycin; Drug Interactions; Drug Therapy, Combination; Erythromycin; Humans; Kidney Failure, Chronic; Metronidazole; Penicillin Resistance; Penicillins; Rifampin; Tetracycline; Tissue Distribution; Vancomycin

Several antimicrobial agents were evaluated for activity against experimental Legionella micdadei pneumonia in guinea pigs. Erythromycin, rifampin, doxycycline, and sulfamethoxazole-trimethoprim produced significant reductions in mortality. Penicillin, cefazolin, cefoxitin, chloramphenicol, and gentamicin were not efficacious even though, at the doses administered, the peak concentrations of these agents in serum substantially exceeded their MICs for the test strain. It is suggested that the poor performance of the latter group of agents resulted from poor penetration into cells in which L. micdadei was multiplying.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cefazolin; Cefoxitin; Chloramphenicol; Doxycycline; Drug Combinations; Erythromycin; Gentamicins; Guinea Pigs; Kinetics; Legionella; Male; Penicillin G; Pneumonia; Rifampin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Large populations of rifampicin-sensitive strains of Mycobacterium tuberculosis have been exposed in vitro to changing concentrations of rifampicin (RIF) in line with changes in the blood level of the drug observed during treatment, and to much lower concentrations. Experiments in which the organism was exposed to either 7 or 14 days of cyclically-changing rifampicin concentrations have resulted in the elimination of the M. tuberculosis test strains without the emergence of RIF resistance. The significance of these laboratory findings is discussed in relation to the debate as to whether rifampicin should be used in short courses for the treatment of non-tuberculous infections or whether it should be withheld for fear of inadvertently generating rifampicin-resistant strains of tubercle bacilli. It is argued that the evidence for withholding rifampicin from use in short courses against non-tuberculous infections is slight.

Topics: Bacterial Infections; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Time Factors

In chronic granulomatous disease (CGD) polymorphonuclear leukocytes (PMN) are unable to kill phagocytized catalase-positive bacteria. Therefore, patients with CGD are prone to infections and dependent on antimicrobial agents able to penetrate PMN membranes and to act intracellularly. Owing to their good lipid solubility, trimethoprim/sulfamethoxazole and rifampicin passively diffuse the membrane. In contrast, fosfomycin is transported actively into the cell. In normal PMN, it reaches cellular-to-extracellular ratios of 1.83 after 15 min, in CGD-PMN 2.18 after 30 min. At concentrations between 16 and 200 mg/liter, fosfomycin was able to kill staphylococci surviving within CGD-PMN, thus compensating for the bactericidal deficiency in CGD. A combination of low concentrations of fosfomycin (8 mg/liter) plus rifampicin (0.06 mg/liter) was more effective at the intracellular level than either agent alone. Apart from a stimulation of PMN-chemiluminescence of yet unknown significance, the agent did not interfere with other neutrophil functions. Clinical investigations are indicated to study whether fosfomycin can be added to the small number of antibiotics useful in CGD.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Biological Transport, Active; Chemotaxis, Leukocyte; Child; Child, Preschool; Female; Fosfomycin; Granulocytes; Granulomatous Disease, Chronic; Humans; Intracellular Fluid; Male; Middle Aged; Neutrophils; Penicillins; Phagocytosis; Rifampin; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim

Laboratory tests of antibiotic activity in vitro, ranging from simple MIC determinations to sophisticated, computerized models for studying the effects of simulated plasma concentration-time curves of antibiotics in broth, differ inherently from tests in vivo in both the general and specific variables. There are therefore likely to be discrepancies between the results obtained. Apart from the obvious lack of host-defence mechanisms in the in-vitro tests systems, the reasons for these discrepancies have still not been fully elucidated. For the time being, it seems unrealistic to expect that in-vitro tests could be developed that would make it possible to predict the efficacy of any antibiotic against any specific infection in vivo.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Disease Models, Animal; Mice; Microbial Sensitivity Tests; Rifampin

Topics: Bacterial Infections; Child; Erythromycin; Female; Granulomatous Disease, Chronic; Humans; Isoniazid; Legionella; Rifampin; Sulfamethoxazole

Topics: Bacterial Infections; Humans; Kinetics; Leprosy; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Seventy out-patients suffering from chronic bacterial prostatitis were treated with a combination of trimethoprim plus rifampicin or trimethoprim alone. A combination of 300 mg. rifampicin plus 160 mg. trimethoprim (rifaprim) was used. Forty-four patients were administered rifaprim at doses of 920 mg. (twice a day) for two months. Twenty-six patients were administered trimethoprim at doses of 320 mg. (twice a day) for two months. Cultures of the expressed prostatic secretions (EPS) yielded gram-positive bacteria in 61 patients and gram-negative bacteria in 9. In rifaprim group, clinical responses were excellent in 9 cases, moderate in 23 cases and poor in 12 cases. The efficacy rate was 73%. In trimethoprim group, excellent in 1 case, moderate in 14 cases and poor in 11 cases. The efficacy rate was 60%. Seven patients of chronic bacterial prostatitis were treated by local injection of tobramycin into the prostate. The antibiotic level in the prostatic fluid twenty-four hours after injection was very high. The pain and discomfort experienced by the patients during injection into the prostate were minimal. Local necrosis was not found after histologic or electron microscopic studies of biopsied prostatic specimen after the injection. Results show that this simple method should be valuable in the treatment of the refractory group of chronic bacterial prostatitis.

Topics: Adult; Bacterial Infections; Chronic Disease; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Injections; Male; Middle Aged; Prostate; Prostatitis; Rifampin; Tobramycin; Trimethoprim

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

Prosthetic valve endocarditis due to Legionella pneumophila occurred in a woman who had aortic and mitral valve replacements with porcine xenografts. During surgery for persistent fever and aortic regurgitation due to presumed endocarditis, she had vegetations involving both the aortic and mitral valve prostheses with a circumferential abscess of the aortic annulus. Cultures, Dieterle stain, and direct fluorescent antibody stain of valve tissue, and subsequent measurements of serum antibody levels confirmed L. pneumophila as the infecting organism. This infection occurred in the absence of pneumonia. Legionella pneumophila must be considered a potential cause of culture-negative prosthetic valve endocarditis and should be sought in appropriate clinical circumstances.

Topics: Aortic Valve; Bacterial Infections; Bioprosthesis; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Female; Heart Valve Prosthesis; Humans; Legionella; Middle Aged; Mitral Valve; Rifampin

A case of Flavobacterium meningosepticum ventriculitis is described in which the failure of therapy with a combination of rifampicin and erythromycin is attributed to inadequate antibiotic levels in cerebrospinal fluid. The successful eradication of the organism was achieved with the use of mezlocillin and cefoxitin given by the intravenous and intraventricular route. In vitro sensitivity tests of recently isolated strains of Flavobacterium meningosepticum suggested that the combination mezlocillin and cefoxitin is more often synergistic than rifampicin and erythromycin.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefoxitin; Cerebral Ventricles; Drug Therapy, Combination; Encephalitis; Erythromycin; Female; Flavobacterium; Humans; Infant; Mezlocillin; Microbial Sensitivity Tests; Penicillins; Rifampin

A parenteral formulation of rifampicin (Rimactan i.v., Ciba-Geigy, Basel, Switzerland) was administered to 237 critically ill or comatose patients, or patients with gastro-intestinal or absorption problems. There were 160 patients suffering from tuberculosis, 77 suffering from non-tuberculous (non-tb) infections including 30 cases of sepsis, 8 cases of bacterial meningitis and/or cerebral abscess and 9 patients with Legionnaires' disease. The usual daily dose of rifampicin was 450-600 mg, administered in most cases by i.v. bolus (122 cases) or i.v. drip infusion (79 cases) for a period of 1-113 days. Rifampicin was in all cases combined with one or more antimicrobial drug(s). The physicians considered the therapy as successful when the treatment with oral rifampicin could be instituted soon after parenteral administration or when the patients markedly improved their clinical condition. Of a total of 123 tuberculous patients for whom assessment of efficacy was possible, 100 (81.3%) showed favourable clinical results. Of 40 non-tb patients who could be analysed for clinical progress, 32 (80.0%) had a favourable outcome. Special attention should be drawn to the 11 patients with proven staphylococcal infections, of whom 10 were cured clinically and/or bacteriologically. Thrombophlebitis occurred in 10 out of the 237 (4.2%) patients, almost always in patients who were treated for more than 30 days. Systemic unwanted effects occurred in 14 (5.9%); the relationship to the treatment was not always established. Treatment was withdrawn due to unwanted effects in 5 (2.1%) of the 237 patients. Taking into account the severe, life-threatening infections reported, the results suggest that i.v. rifampicin is useful and in some critically ill patients even life-saving. Tolerability was good, even in long-term i.v. administration, although there seems to be the possibility that thrombophlebitis might develop if treatment is continued over 30 days.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Rifampin; Tuberculosis

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Humans; Infusions, Parenteral; Intensive Care Units; Middle Aged; Rifampin; Suppuration

Topics: Bacterial Infections; Erythromycin; Female; Flavobacterium; Humans; Infant; Meningitis; Rifampin

A combined kinetic and clinical study showed that rifampicin displays good tissue diffusibility, though it may have a tendency to accumulate. A liquor transfer sufficient for the bacteria most commonly responsible for meningeal inflammation was observed; 15/18 cases of purulent bacterial meningitis treated were clinically cured without sequelae, while 1 displayed considerable improvement. Two patients died from unforseen, uncontrollable complications that were not related to administration of the drug.

Topics: Adolescent; Adult; Bacterial Infections; Child; Drug Evaluation; Female; Humans; Infusions, Parenteral; Kinetics; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Rifampin; Tissue Distribution

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infusions, Parenteral; Male; Middle Aged; Rifampin; Staphylococcal Infections; Tuberculosis; Tuberculosis, Pulmonary

DL 473, a new semisynthetic rifamycin, was 2-10 times more active in vitro than rifampicin (RAMP) against several clinical isolates of Mycobacterium tuberculosis and only slightly less active than RAMP against Gram-positive and Gram-negative bacteria. It showed excellent therapeutic activity in mice in experimental infections caused by Staphylococcus aureus, Streptococcus pyogenes group A, Streptococcus pneumoniae and Klebsiella pneumoniae. In the experimental TB infection in the mouse DL 473 was clearly more active than isoniazide and RAMP, two of the most effective antitubercular drugs in current use. The LD50 in the mouse was significantly higher than that of RAMP and the half-life was about 5 times longer than that of RAMP.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Dose-Response Relationship, Drug; Isoniazid; Mice; Microbial Sensitivity Tests; Rifampin; Tuberculosis

The course of fever was examined in 75 patients with pulmonary tuberculosis treated with modern chemotherapy. Sixteen patients (21%) were afebrile and differed from 59 febrile patients (79%) by having lower incidences of the following: symptoms (p < 0.02), alcoholism (p < 0.01), lung cavitation (p < 0.01), "far advanced disease" (p < 0.05), and sputum smears containing "numerous" acid-fast bacilli (p < 0.01). Resolution of fever was variable (mean, 16 days; median, 10 days; range, 1 to 109 days). Thirty-eight patients (64%) became afebrile within 2 wk (group 1); 21 (36%) had fever for longer than 2 wk (group 2). Far advanced disease and high temperature (> 38.8 degrees C) on admission were more frequent in group 2 (p < 0.05 and p < 0.01, respectively). However, the groups did not differ in demographic features or in the frequency of symptoms on admission, alcoholism, lung cavitation, numerous acid-fast bacilli on sputum smears, or coexisting bacterial respiratory infection. Antimicrobial drug treatment of presumed coexistent bacterial infection in 19 febrile patients did not influence the course of fever. Analysis of variance and covariance were used to compare the independent effects of various antituberculosis drug regimens on the course of fever; no significant differences were observed.

Topics: Alcoholism; Antitubercular Agents; Bacterial Infections; Drug Therapy, Combination; Ethambutol; Female; Fever; Humans; Isoniazid; Lung; Male; Middle Aged; Rifampin; Sputum; Streptomycin; Time Factors; Tuberculosis, Pulmonary

589 isolates of anaerobic bacteria, including 127 isolates of Bacterioides fracilis, were tested against 23 antimicrobial agents. At their usually achievable serum levels, carbenicillin, ticarcillin, mezlocillin and piperacillin; cefoxitin, minocycline, doxycycline, clindamycin, chloramphenicol and rifampin were effective against more than 80% of B. fragilis isolates. At usual therapeutic doses, penicillin (PEN), ampicillin (AMP), cyclacillin (CYC), cephalothin (CT), cefazolin (CZ), cephradine (CPD), cefamandole (CMD), cefaclor (CCL), cefuroxime (CRX), spectinomycin (SPT), tetracycline (TET), ethambutol (EMB) and isoniazid (INH) were ineffective against B. Fragilis. However, high and clinically tolerated doses of PEN, CMD and SPT inhibited more than 80% of B. fragilis isolates, but AMP, CYC, CT, CZ, CPD, CCL and CRX, TET, EMB and INH remained totally ineffective against B. fragilis. The therapeutic merits of these antibiotics are discussed.

Topics: Anaerobiosis; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteroides fragilis; beta-Lactamases; Cephalosporins; Chloramphenicol; Clindamycin; Ethambutol; Humans; Isoniazid; Microbial Sensitivity Tests; Penicillins; Rifampin; Spectinomycin; Tetracyclines

The presence of allugtinins to the causative organism of contagious equine metritis (C.E.M.) in human serum has been confirmed. Agglutinins were found in the serum of 84 (37.6%) of 223 patients with non-gonococcal urethritis (N.G.U.), and in 12.5% of these patients there was a four-fold or greater rise in titre during the course of their illness. There was no evidence that these agglutinins were the result of infection by chlamydiae or ureaplasmas. Certain patients with these agglutinins seemed to respond better to therapy with antibiotics to which the C.E.M. bacterium is susceptible in vitro than did patients in whom these agglutinins were not found. The findings suggest that the C.E.M. bacterium or a microorganism related to it may be aetiologically involved in a proportion of patients with N.G.U. A search for such an organism in these patients is in progress.

Topics: Agglutination Tests; Agglutinins; Animals; Antibodies, Bacterial; Bacterial Infections; Endometritis; Female; Horse Diseases; Horses; Humans; In Vitro Techniques; Male; Minocycline; Rifampin; Urethritis

Topics: Adult; Aged; Bacterial Infections; Female; Humans; Kidney Diseases; Male; Middle Aged; Neomycin; Rifampin; Urinary Tract Infections

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Microbial; Drug Stability; Mice; Microbial Sensitivity Tests; Naphthalenes; Rifampin

It has tested the effect of Rifamicina SV in the cystolusis employed on patients with permanent catheter: compared to the treatment with physiological solution this one, with Rifamicina SV, has showed, in most cases, the lower incidence of urine bacteria and their quick negative answer. This by an only local theatment. During the experiment has also been showed the possibility for the Rifamicina SV of selecting the Citrobacter as a resistant bacterial species.

Topics: Bacterial Infections; Humans; Rifampin; Urinary Catheterization; Urinary Tract Infections

Topics: Bacterial Infections; Drug Evaluation; Humans; Rifampin; Tuberculosis

Topics: Animals; Bacterial Infections; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Guinea Pigs; Humans; Rifampin; Trimethoprim; Tuberculosis

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

Topics: Anaerobiosis; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; Cephalosporins; Chloramphenicol; Clindamycin; Clostridium; Erythromycin; Fusobacterium; Gram-Negative Anaerobic Bacteria; Humans; Lincomycin; Metronidazole; Penicillin Resistance; Penicillins; Rifampin; Tetracycline; Thiamphenicol; Vancomycin

Topics: Adult; Aged; Bacterial Infections; Drug Evaluation; Female; Humans; Male; Middle Aged; Rifampin

Topics: Bacterial Infections; Humans; Intestinal Absorption; Kidney; Liver; Rifampin; Urinary Tract Infections

Topics: Adult; Aged; Bacterial Infections; Female; Humans; Lung Diseases; Male; Middle Aged; Postoperative Complications; Rifampin; Sepsis; Urinary Tract Infections

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: Administration, Oral; Adult; Aged; Bacterial Infections; Bile; Cholecystitis; Drug Resistance, Microbial; Escherichia coli; Female; Humans; Klebsiella; Male; Middle Aged; Pyelonephritis; Rifampin; Urinary Tract Infections

Topics: Actinomyces; Actinomycosis; Anaerobiosis; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriological Techniques; Bacteroides; Bacteroides Infections; Carbon Dioxide; Chloramphenicol; Clindamycin; Clostridium; Erythromycin; Female; Humans; Hydrogen-Ion Concentration; Lincomycin; Maternal-Fetal Exchange; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Placenta; Pregnancy; Rifampin; Tetracycline

Topics: Actinomycetales Infections; Anaerobiosis; Anti-Bacterial Agents; Bacterial Infections; Bacteroides Infections; Cephalosporins; Chloramphenicol; Clindamycin; Clostridium Infections; Erythromycin; Fusobacterium; Humans; Lincomycin; Metronidazole; Microbial Sensitivity Tests; Oxygen; Penicillins; Rifampin; Streptococcal Infections; Tetracycline; Treponemal Infections; Vancomycin; Veillonella

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cephalothin; Child; Child, Preschool; Chlortetracycline; Gentamicins; Humans; Infant; Neomycin; Penicillins; Respiratory Tract Infections; Rifampin; Streptomycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Humans; Penicillin Resistance; Penicillins; Polymyxins; Rifampin; Spectinomycin

Topics: Bacterial Infections; Gonorrhea; Humans; Rifampin; Urethritis

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbenicillin; Cephalexin; Clindamycin; Doxycycline; Gentamicins; Microbial Sensitivity Tests; Minocycline; Rifampin; Sulfamethoxazole; Tetracycline; Trimethoprim

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: Bacterial Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Rifampin

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloglycin; Cephalosporins; Enterobacteriaceae Infections; Gentamicins; Humans; Pseudomonas Infections; Rifampin; Staphylococcal Infections