minocycline and Cross-Infection

Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases.. We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed.. In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009).. Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Minocycline; Respiratory Tract Infections; Retrospective Studies; Tigecycline; Treatment Outcome

Treatment of Acinetobacter baumannii has become a medical challenge because of the increasing incidence of multiresistant strains and a lack of viable treatment alternatives. This systematic review attempts to investigate the changes in resistance of A. baumannii to different classes of antibiotics in Iran, with emphasis on the antimicrobial activity of polymyxin B (PMB) and colistin (COL). Biomedical databases were searched for English-published articles evaluating microbiological activity of various antimicrobial agents, including PMB and COL. Then, the available data were extracted and analyzed. Thirty-one studies, published from 2009 to 2015, were identified which contain data for 3,018 A. baumannii clinical isolates. With the exception of polymyxins and tigecycline (TIG), there was a high rate of resistance to various groups of antibiotics, including carbapenems. The minimum inhibitory concentration (MIC) ranges for PMB and COL on A. baumannii isolates tested were 0.12-64 μg/ml and 0.001-128 μg/ml, respectively. Polymyxins showed adequate activity with no significant trends in the resistance rate during most of the study period. The incidence of resistance to TIG was estimated low from 2% to 38.4% among the majority of A. baumannii. The present systematic review of the published literatures revealed that multidrug-resistant (including carbapenem-resistant) strains of A. baumannii have increased in Iran. In these circumstances, the older antibiotics, such as COL or PMB, preferably in combination with other antimicrobials (rifampicin, meropenem), could be considered as the therapeutic solution against the healthcare-associated infections. Designing rational dosage regimens for patients to maximize the antimicrobial activity and minimize the emergence and prevalence of resistance is recommended.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Iran; Meropenem; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Rifampin; Thienamycins; Tigecycline

The wide dissemination of carbapenemase producing K. pneumoniae (KPC-Kp) has caused a public health crisis of global dimensions, due to the serious infections in hospitalized patients associated with high mortality. In 2014, we aim to review clinical data on KPC-Kp at a time when a pro-active strategy (combating the problem before it is established) is no longer useful, focusing on epidemiology, patient risk profile, infection control, digestive tract colonization and treatment issues such as the role of carbapenems or carbapenem sparing strategies, colistin and resistance, dual carbapenem administration and the role of tigecycline. All these issues are illustrated prospectively to provide a forum for a Consensus strategy when not only intensive care units but also medical and surgical wards are affected by the epidemics.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Drug Therapy, Computer-Assisted; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Risk Factors; Tigecycline

Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial infection at a high mortality rate. Nosocomial pneumonia in particular is associated with high mortality, likely due to the unfavorable pulmonary pharmacokinetics of the antibiotics used against this agent. Therefore, early and accurate microbiological identification and susceptibility evaluation are crucial in order to optimize antibiotic therapy. We report a case of ventilator-associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC-type carbapenemase treated using a carbapenem-sparing therapy and tailored according to the serum procalcitonin concentration in order to limit the duration of antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Calcitonin; Calcitonin Gene-Related Peptide; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Equipment Contamination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Pneumonia, Bacterial; Protein Precursors; Tigecycline; Treatment Outcome; Ventilators, Mechanical

To review cases of multidrug-resistant (MDR) Gram-negative bacillus urinary tract infections (UTIs) treated with tigecycline and the literature related to this subject.. We performed a systematic review of the literature identifying patients with MDR Gram-negative bacillus UTIs treated with tigecycline.. Fourteen cases describing treatment of UTIs caused by MDR Gram-negative bacilli with tigecycline are reviewed. Favourable clinical outcomes were noted in 11 of 14 cases. An initial favourable microbiological outcome was noted in 12 cases. Post-treatment cultures in two cases were positive for tigecycline-resistant organisms.. The clinical efficacy of tigecycline for treatment of UTIs has not been extensively evaluated. Based on the available literature, tigecycline appears to have efficacy in some patients with MDR Gram-negative bacillus UTIs. Further research in this area is needed to fully elucidate the role of tigecycline in treating such patients.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Humans; Male; Minocycline; Risk Factors; Tigecycline; Treatment Outcome; Urinary Tract Infections

Carbapenem-resistant Enterobacteriaceae are a group of virulent, drug-resistant gram-negative bacteria that are increasingly the cause of infection. Such infections are associated with a high morbidity and mortality and increased health care costs. Management of these infections requires recognition of patients at risk for multidrug-resistant microbial colonization and infections, identification of the causative organism, and rapid, appropriate treatment. Lack of awareness of proper isolation of patients harboring these organisms and delay in prescribing antibiotics such as tigecycline and polymyxins contribute to the spread of infection in intensive care units. Surveillance and infection control measures are paramount in preventing outbreaks of infection caused by carbapenem-resistant Enterobacteriaceae. Critical care nurses are in a vital position to monitor patients at risk for such infections and to promote infection prevention measures.

Topics: Anti-Bacterial Agents; Carbapenems; Critical Care Nursing; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Humans; Infection Control; Intensive Care Units; Minocycline; Sepsis; Tigecycline

Tigecycline is indicated for the treatment of complicated skin infections, soft tissue and intraabdominal infections. Its use could be extended to community-acquired pneumonia (CAP) and hospital pneumonia (HN). The objective was to evaluate the efficacy and safety of tigecycline in the treatment of respiratory infections.. systematic review (2012). Databases used were MEDLINE, EMBASE, Cochrane Library, CRD and WOK. We identified clinical trials of adults with respiratory infection, treated with tigecycline. The quality of the studies was assessed using CASPe checklist.. We selected four clinical trials of high-moderate quality. Three studies with patients with CAP and a trial with HN patients. In patients with CAP, efficacy of tigecycline (88.6 to 90.6%) was higher than levofloxacin (85.3 to 87.2%). The non inferiority testing was statistically significant (p < 0.001). In the study of patients with HN tigecycline showed an efficiency of 67.9% versus 78.2% for imipenem/cilastatin. Main adverse effects were gastrointestinal.. The efficacy of tigecycline is non inferior than levofloxacin in patients with CAP, but less than imipenem in patients with HN. Tigecycline demonstrates noninferiority versus others tested antibiotics, and it shows a good safety profile.

Topics: Adult; Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Cross Infection; Humans; Minocycline; Pneumonia; Respiratory Tract Infections; Tigecycline

Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens in the nosocomial and community setting. Hospitalization costs associated with MRSA infections are substantially greater than those associated with methicillin-sensitive S. aureus (MSSA) infections, and MRSA has wider economic effects that involve indirect costs to the patient and to society. In addition, there is some evidence suggesting that MRSA infections increase morbidity and the risk of mortality. Glycopeptides are the backbone antibiotics for the treatment of MRSA infections. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Several new antimicrobials demonstrate in vitro activity against MRSA and other Gram-positive bacteria. Data from large surveys indicate that linezolid, daptomycin, and tigecycline are almost universally active against MRSA. This review will briefly discuss the epidemiology, costs, outcome, and therapeutic options for the management of MRSA infections.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Cross Infection; Daptomycin; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Staphylococcal Infections; Tigecycline; Treatment Outcome

This article reviews the clinical experience with tigecycline in the treatment of infections caused by microorganisms with prevalent resistance mechanisms among nosocomial microbiota, as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, multidrug- resistant Acinetobacter baumannii and enterobacteria producing extended spectrum beta-lactamases. Most of articles found in the literature describe the use of tigecycline in the treatment of severe infections (sepsis and septic shock, nosocomial pneumonia and ventilator-associated pneumonia...) produced by multidrug-resistant microorganisms, in patients with multiple comorbidities (admitted in ICU, with malignancies, transplants and/or immunodepressed...) and in many occasions after failures of previous antibiotic treatments. Favourable outcomes with tigecycline are reported in most articles. However, an accurate global assessment is difficult since, in addition to the described confounding factors, there are concomitant or sequential antibiotic treatments in several communications, and lack of relevant clinical (as comorbidities), microbiological (as susceptibility) and outcome (different criteria by different authors) data in others. More even, the described series are retrospective and lack of control groups. Nevertheless the usefulness of this revision is based on the fact that in daily clinical practice the use of tigecycline will increase, since epidemiology of specific hospital medical units shows multidrug resistance among nosocomial isolates and tigecycline can be one of the scarce available compounds active against multidrug-resistant strains/clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Minocycline; Tigecycline

Therapeutic strategies in the management of skin and soft tissue infections should take account of different variables: epidemiological trends (community or hospital acquired infections), pathogen or pathogens involved, virulence, seriousness of pathology (possible co-morbidities, knowledge of local epidemiology and antimicrobial susceptibility patterns of community and hospital strains. Therapy often should be started promptly, and on an empiric base, once microbiological analysis have been performed, waiting for culture and antimicrobial susceptibility testing. Surgical incision and drainage represent essential therapeutic procedures in the treatment of many complicated skin and soft tissue infections such as abscesses and fasciitis. Gram-positive bacteria and specifically Staphylococcus aureus, are the main cause of such kind of infections. Therefore antistaphylococcal beta-lactams represents a first choice in empirical antimicrobial chemotherapy. Considering high incidence of MRSA in Italian hospitals, treatment of hospital acquired skin and soft tissue infections should be based on glycopeptides combined with third generation cephalosporins, piperacillin-tazobactam, carbapenems or fluoroquinolones. Recently, new drugs (as linezolid, daptomycin, tigecycline) demonstrated good efficacy in the treatment of serious infections caused by multi-drug resistant microorganisms. Most recent guidelines for the diagnosis and treatment of skin and soft tissue infections were published in 2005 by Infectious Diseases Society of America (IDSA). In Italy, the multidisciplinary group of Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) published guidelines for the treatment of skin and soft tissue infections in Internal Medicine wards in 2005. General approach and methodology in writing test were based on analysis of data from available scientific literature and comparing them with actual Italian epidemiological trends and drug prescribing policy. Considering these guidelines, we updated the newest antimicrobial drugs suggested for the treatment of skin and soft tissue infections, such as daptomycin and tigecycline.

Topics: Acetamides; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Cross Infection; Daptomycin; Debridement; Drainage; Drug Therapy, Combination; Humans; Italy; Linezolid; Minocycline; Oxazolidinones; Practice Guidelines as Topic; Sepsis; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Wound Infection

Traditionally, pneumonia is categorized by epidemiologic factors into community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Microbiologic studies have shown that the organisms which cause infections in HAP and VAP differ from CAP in epidemiology and resistance patterns. Patients with HAP or VAP are at higher risk for harboring resistant organisms. Other historical features that potentially place patients at a higher risk for being infected with resistant pathogens and organisms not commonly associated with CAP include history of recent admission to a health care facility, residence in a long-term care or nursing home facility, attendance at a dialysis clinic, history of recent intravenous antibiotic therapy, chemotherapy, and wound care. Because these "risk factors" have health care exposure as a common feature, patients presenting with pneumonia having these historical features have been more recently categorized as having health care-associated pneumonia (HCAP). This publication was prepared by the HCAP Working Group, which is comprised of nationally recognized experts in emergency medicine, infectious diseases, and pulmonary and critical care medicine. The aim of this article is to create awareness of the entity known as HCAP and to provide knowledge of its identification and initial management in the emergency department.

Topics: Acetamides; Age Distribution; Aged; Aged, 80 and over; Anti-Infective Agents; beta-Lactams; Cephalosporins; Cross Infection; Emergency Treatment; Ertapenem; Female; Humans; Length of Stay; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Oxazolidinones; Patient Care Team; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Practice Guidelines as Topic; Respiration, Artificial; Risk Factors; Severity of Illness Index; Tigecycline

Acinetobacter baumannii (AB) is a gram-negative organism that has emerged recently as a major cause of nosocomial infections, because of the extent of its antimicrobial resistance and its persistence in the hospital environment, where intensive care units are the place of greatest risk for acquiring AB. There is no treatment of choice for AB and it's treatment is based on clinical experience and in vitro susceptibility testing. Also, nowadays Acinetobacter resistance to carbapenems is common and isolates resistant to colistin and polymyxin B have been reported. Tigecycline, the 9-tert-butyl-glycylamido derivative of minocycline, exhibits a broad-spectrum of activity against numerous pathogens, including AB and several reports place it among the antimicrobials with lower MIC for AB. Tigecycline overcomes the two major mechanisms of resistance to tetracyclines (ribosomal protection and efflux), but tigecycline resistance emerging during therapy has been reported. Tigecycline efficacy has been demonstrated in clinical studies in skin and skin structure infections and in complicated intra-abdominal infections but, although it seems a good alternative for the treatment of AB infections, there is few evidence about its use in these cases and more clinical experience and adequate trials are needed. The present review shows the recent patents related to treatment by tigecycline in different AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Structure; Patents as Topic; Structure-Activity Relationship; Tigecycline; Treatment Outcome

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of gram-positive, gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of vancomycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Interactions; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Tigecycline

Acinetobacter baumannii is an important cause of nosocomial infections, mainly in patients in intensive care units. This microorganism, although with slight differences depending on the country, presents resistance to multiple antimicrobial agents, occasionally including resistance to colistin: hence, it can be considered the paradigm of nosocomial multiresistant bacteria. This review analyzes the evolution of antimicrobial resistance and the molecular bases associated with the increase in antimicrobial resistance, as well as the current treatment of Acinetobacter infections. Although controversy remains, the pooled data suggest that infections by A. baumannii may be associated with considerable attributable mortality. Moreover, in cases of pneumonia and bacteraemia, inappropriate treatment is associated with, among other factors, mortality. Therefore, treatment should be carefully considered.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Minocycline; Patient Selection; Rifampin; Sulbactam; Tigecycline; Treatment Outcome

Bloodstream infection related to a central venous catheter is a substantial clinical and economic problem. To develop policy for managing the risks of these infections, all available evidence for prevention strategies should be synthesized and understood.. We evaluate evidence (1985-2006) for short-term antimicrobial-coated central venous catheters in lowering rates of catheter-related bloodstream infection (CRBSI) in the adult intensive care unit. Evidence was appraised for inclusion against predefined criteria. Data extraction was by 2 independent reviewers. Thirty-four studies were included in the review. Antiseptic, antibiotic, and heparin-coated catheters were compared with uncoated catheters and one another. Metaanalysis was used to generate summary relative risks for CRBSI and catheter colonization by antimicrobial coating.. Externally impregnated chlorhexidine/silver sulfadiazine catheters reduce risk of CRBSI relative to uncoated catheters (RR, 0.66; 95% CI: 0.47-0.93). Minocycline and rifampicin-coated catheters are significantly more effective relative to CHG/SSD catheters (RR, 0.12; 95% CI: 0.02-0.67). The new generation chlorhexidine/silver sulfadiazine catheters and silver, platinum, and carbon-coated catheters showed nonsignificant reductions in risk of CRBSI compared with uncoated catheters.. Two decades of evidence describe the effectiveness of antimicrobial catheters in preventing CRBSI and provide useful information about which catheters are most effective. Questions surrounding their routine use will require supplementation of this trial evidence with information from more diverse sources.

Topics: Anti-Bacterial Agents; Carbon; Catheterization; Catheterization, Central Venous; Chlorhexidine; Cross Infection; Humans; Intensive Care Units; Minocycline; Platinum; Rifampin; Sepsis; Silver

The emergence and spread of multidrug resistance in many pathogenic bacterial species is increasing at an alarming rate, especially with hospital-acquired infections in the critical care setting. Deaths associated with hospital-acquired infections have exceeded the number attributable to several of the top 10 leading causes of death reported in the United States. The emerging resistance limits the use of older antibiotics. Tigecycline is a new agent, and this article explores its role in the treatment of adults in the critical care setting.

Topics: Adult; Anti-Bacterial Agents; Costs and Cost Analysis; Critical Care; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Randomized Controlled Trials as Topic; Tigecycline; United States

Tigecycline is a new antimicrobial agent; it is the first in a new class of antibiotics, the glycylcyclines, with properties conferring the ability to overcome many common resistance mechanisms, thus allowing its use for many serious and life-threatening infections for which the use of other antibiotics is no longer appropriate. It has a wide antibacterial spectrum including most methicillin-resistant Staphylococci, vancomycin-resistant Enterococci, ESBL-producing Gram negative bacteria, and other MDR Gram negative bacteria such as Acinetobacter, and Stenotrophomonas. It has good antibacterial activity also against anaerobes and atypical pathogens. Tigecycline is available only as parenteral formulation. It has a high volume of distribution (>10 l/kg), and long half-life (36 hrs). It has been approved in USA and Europe for the treatment of complicated skin and soft tissue infections and for the complicated community acquired intra-abdominal infections. Phase III studies for treatment of community acquired and nosocomial acquire pneumonia, and sepsis sustained by multi-drug-resistant pathogens are ongoing.

Topics: Abdominal Cavity; Anti-Bacterial Agents; Cross Infection; Digestive System Diseases; Humans; Injections, Intravenous; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

Complicated intra-abdominal infections remain a major challenge for surgeons and internists because of their association with high morbidity and mortality. For optimal outcome, these infections require a combination of appropriate and timely surgical source control and adjunctive broad-spectrum antimicrobial therapy. This review discusses criteria for choosing empiric antimicrobial therapy, outlines available treatment options, and highlights new antimicrobial therapies for these infections.

Topics: Anti-Bacterial Agents; Carbapenems; Community-Acquired Infections; Cross Infection; Doripenem; Drug Resistance, Bacterial; General Surgery; Humans; Internal Medicine; Minocycline; Peritoneal Cavity; Peritonitis; Risk Factors; Severity of Illness Index; Surgical Wound Infection; Tigecycline

Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that thrives within the unique and complex ecological setting of an intensive care unit. This evolving pathogen has now surpassed human capacity to create new antimicrobials, and has led physicians into a concerning era for hospital-acquired infections. This review presents the available evidence on the therapeutic strategies for A. baumannii infection, with a particular focus on clinical human data. The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline. Other important adjunctive strategies such as pharmacodynamic target attainment and infection control implementation are briefly discussed. It is now clear that new antimicrobials with unique mechanisms of action are urgently required to combat the rising trends seen globally with drug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Intensive Care Units; Minocycline; Polymyxins; Sulbactam; Tigecycline

Surgical site infections are the third most common healthcare-associated infection, often leading to prolonged hospital stay and excessive expenditures. Management of these infections has become more challenging due to rising rates of multi-drug-resistant organisms and few new antibiotic options.. This paper reviews the literature, summarizes the epidemiology of surgical site infections and the threat of antibiotic-resistant bacteria, and provides an insight into new treatment options for this condition.. Patients with surgical site infections are at greater risk of acquiring healthcare-associated antibiotic-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) sp., and extended-spectrum beta-lactamase-(ESBL)-producing Escherichia coli and Klebsiella pneumoniae. Multi-drug-resistant Pseudomonas aeruginosa and Bacteroides fragilis are also a growing problem. Several useful drugs have recently become available for the management of serious, gram-positive infections (e.g., daptomycin, linezolid, telithromycin). Tigecycline, the first-in-class glycylcycline, has broad-spectrum in vitro activity, including against MRSA, VRE, resistant enteric gram-negative bacilli (e.g., Acinetobacter sp.), "atypical" pathogens, and anaerobes. Phase 3 clinical trials suggest that tigecycline will be an excellent option for antibiotic monotherapy for complicated skin and soft tissue infections (cSSSI) and intra-abdominal infections. Oritavancin and dalbavacin, two novel glycopeptide antibiotics that are also in late-stage clinical development, appear that they, too, will be useful for cSSSI due to resistant, gram-positive bacteria.. Multi-drug-resistant pathogens are threatening the success of available antibiotic therapy. Many new options are useful for infections due to multi-drug-resistant, gram-positive bacteria. Tigecycline is a promising new agent that provides coverage against a broad spectrum of gram-positive and gram-negative, aerobic, facultative, and anaerobic strains, including resistant isolates, and may make broad-spectrum, single-agent therapy possible.

Topics: Acetamides; Acinetobacter; Anti-Bacterial Agents; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Humans; Ketolides; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pseudomonas aeruginosa; Surgical Wound Infection; Tigecycline; Vancomycin Resistance

Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.42 times higher for patients with fAUC(0-24):MIC ratios of ≥0.9 compared to patients with fAUC(0-24):MIC ratios of <0.9 (P = 0.008). Average model-estimated probabilities of clinical success for the albumin/fAUC(0-24):MIC ratio combinations of <2.6/<0.9, <2.6/≥0.9, ≥2.6/<0.9, and ≥2.6/≥0.9 were 0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status. The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (P < 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (P = 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC(50)and MIC(90) values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively; P = 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Cross Infection; Double-Blind Method; Female; Gram-Negative Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Staphylococcus aureus; Tigecycline; Treatment Outcome; Young Adult

Antimicrobial drug development has greatly diminished due to regulatory uncertainty about the magnitude of the antibiotic treatment effect. Herein we evaluate the utility of pharmacometric-based analyses for determining the magnitude of the treatment effect. Frequentist and Bayesian pharmacometric-based logistic regression analyses were conducted by using data from a phase 3 clinical trial of tigecycline-treated patients with hospital-acquired pneumonia (HAP) to evaluate relationships between the probability of microbiological or clinical success and the free-drug area under the concentration-time curve from time zero to 24 h (AUC(0-24))/MIC ratio. By using both the frequentist and Bayesian approaches, the magnitude of the treatment effect was determined using three different methods based on the probability of success at free-drug AUC(0-24)/MIC ratios of 0.01 and 25. Differences in point estimates of the treatment effect for microbiological response (method 1) were larger using the frequentist approach than using the Bayesian approach (Bayesian estimate, 0.395; frequentist estimate, 0.637). However, the Bayesian credible intervals were tighter than the frequentist confidence intervals, demonstrating increased certainty with the former approach. The treatment effect determined by taking the difference in the probabilities of success between the upper limit of a 95% interval for the minimal exposure and the lower limit of a 95% interval at the maximal exposure (method 2) was greater for the Bayesian analysis (Bayesian estimate, 0.074; frequentist estimate, 0.004). After utilizing bootstrapping to determine the lower 95% bounds for the treatment effect (method 3), treatment effect estimates were still higher for the Bayesian analysis (Bayesian estimate, 0.301; frequentist estimate, 0.166). These results demonstrate the utility of frequentist and Bayesian pharmacometric-based analyses for the determination of the treatment effect using contemporary trial endpoints. Additionally, as demonstrated by using pharmacokinetic-pharmacodynamic data, the magnitude of the treatment effect for patients with HAP is large.

Topics: Anti-Bacterial Agents; Area Under Curve; Bayes Theorem; Biomarkers, Pharmacological; Cross Infection; Gram-Positive Bacteria; Humans; Logistic Models; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Double-Blind Method; Drug Combinations; Hospital Mortality; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Pneumonia; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

Tigecycline is a new-generation of tetracycline (glycylcyclines) and is active in vitro against bacteria that possess any of the classical genes that confer tetracycline resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition in patients with community- or hospital-acquired pneumonia was described using a population pharmacokinetic model. Additionally, the influence of covariates, such as body surface area, severity of illness, and clinical laboratory measures, on tigecycline disposition was evaluated. An intravenous loading dose of 100 mg was followed by 50 mg of tigecycline every 12 h. The final population pharmacokinetic model was a two-compartment model with linear elimination and with a relationship between tigecycline clearance and body surface area and creatinine clearance. The model was parameterized using total clearance (CL), the volume of the central compartment, distributional clearance from the central to the peripheral compartment, and volumes of distribution at steady state. Relationships between body surface area and creatinine clearance were identified as significant predictors of interindividual variability on CL. This model will serve as the basis for estimating tigecycline exposure for pharmacokinetic-pharmacodynamic analyses for efficacy and safety among patients with community- or hospital-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia; Tigecycline; Young Adult

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection.. A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment.. For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid.. Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.

Topics: Acetamides; Aged; Anti-Bacterial Agents; Cross Infection; Double-Blind Method; Enterococcus; Female; Gram-Positive Bacterial Infections; Hospitalization; Humans; Linezolid; Male; Methicillin Resistance; Middle Aged; Minocycline; Oxazolidinones; Staphylococcus aureus; Tigecycline; Treatment Outcome; Vancomycin; Vancomycin Resistance

Central venous catheters are the predominant cause of nosocomial bacteremia; however, the effectiveness of different antimicrobial central venous catheters remains uncertain. We compared the infection rate of silver-platinum-carbon (SPC)-impregnated catheters with rifampicin-minocycline (RM)-coated catheters.. A large, single-center, prospective randomized study.. Twenty-two-bed adult general intensive care unit in a large tertiary metropolitan hospital in Brisbane, Australia (2000-2001).. Consecutive series of all central venous catheterizations in intensive care unit patients.. Randomization, concealment, and blinding were carefully performed. Catheter insertion and care were performed according to published guidelines. Blood cultures were taken at central venous catheter removal, and catheter-tip cultures were performed by both roll-plate and sonication techniques. Pulsed field gel electrophoresis was used to establish shared clonal origin for matched isolates.. Central venous catheter colonization and catheter-related bloodstream infection were determined with a blinded technique using the evaluation of the extensive microbiological and clinical data collected and a rigorous classification system. Six hundred forty-six central venous catheters (RM 319, SPC 327) were inserted, and 574 (89%) were microbiologically evaluable. Colonization rates were lower for the RM catheters than SPC catheters (25 of 280, 8.9%; 43 of 294, 14.6%; p=.039). A Kaplan-Meier analysis that included catheter time in situ did not quite achieve statistical significance (p=.055). Catheter-related bloodstream infection was infrequent for both catheter-types (RM 4, 1.4%; SPC 5, 1.7%).. The SPC catheter is a clinically effective antimicrobial catheter; however, the RM catheter had a lower colonization rate. Both catheter types had low rates of catheter-related bloodstream infection. These results indicate that future studies will require similar rigorous methodology and thousands of central venous catheters to demonstrate differences in catheter-related bloodstream infection rates.

Topics: Anti-Infective Agents, Local; Bacteremia; Carbon; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Equipment Contamination; Female; Humans; Logistic Models; Male; Middle Aged; Minocycline; Platinum; Prospective Studies; Queensland; Rifampin; Silver

We previously demonstrated that minocycline-EDTA was efficacious at preventing catheter-related bloodstream infections (BSIs) in three patients with recurrent infections. This study compared heparin with minocycline-EDTA as flush solutions used among dialysis patients with central venous catheters, a high-risk group for catheter-related BSI.. Patients were enrolled within 72 hours of catheter insertion and randomized to receive heparin or minocycline-EDTA as a flush after each dialysis session. Each syringe containing flush solution was wrapped in orange plastic to conceal the type of solution it contained. Patients were observed for evidence of infection and catheter thrombosis. After catheters were removed, cultures were performed to determine whether microbial colonization had occurred.. During a 14-month period, 60 patients were enrolled (30 in each group). The two groups had similar demographics and underlying diseases. Catheter survival at 90 days was 83% for the minocycline-EDTA group versus 66% for the heparin group (P = .07). Significant catheter colonization, a surrogate measure of catheter-related infection, was significantly more frequent in the heparin group (9 of 14 vs 1 of 11; P = .005). There was only one catheter-related bacteremia and it occurred in the heparin group.. When compared with heparin, minocycline-EDTA had a better 90-day catheter survival (P = .07) and a decreased rate of catheter colonization. This pilot study warrants a larger prospective, randomized trial.

Topics: Anti-Bacterial Agents; Anticoagulants; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Double-Blind Method; Drug Combinations; Edetic Acid; Equipment Contamination; Female; Heparin; Humans; Infection Control; Male; Middle Aged; Minocycline; North Carolina; Pilot Projects; Prospective Studies; Renal Dialysis; Risk Factors; Sepsis; Survival Analysis; Therapeutic Irrigation; Thrombosis; Time Factors

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

Elizabethkingia meningoseptica is a non-fermentative Gram-negative bacillus that has emerged as an important pathogen in nosocomial infections and is usually associated with high mortality. E. meningoseptica is inherently resistant to many broad-spectrum antibiotics, and appropriate antibiotic selection is crucial for survival. Data about the therapeutic efficacy of fluoroquinolone in E. meningoseptica bacteraemia are limited. We retrospectively enrolled patients with E. meningoseptica bacteraemia who were treated with a single antimicrobial agent with in vitro activity against E. meningoseptica for at least 48 hours in a Taiwanese medical centre between January 2011 and June 2016. We compared the therapeutic efficacy of fluoroquinolone and non-fluoroquinolone treatment. A logistic regression and a propensity score-adjusted model were used to evaluate the risk factors for 14-day mortality. A total of 66 patients were identified, 24 who received fluoroquinolone treatment (ciprofloxacin, n = 9; levofloxacin, n = 15) and 42 who received non-fluoroquinolone treatment (piperacillin/tazobactam, n = 26; trimethoprim/sulfamethoxazole, n = 15; minocycline, n = 1). The fluoroquinolone group had significantly lower 14-day mortality than the non-fluoroquinolone group (8.3% vs. 33.3%, P = 0.023). The APACHE II score was significantly higher in the non-fluoroquinolone group than in the fluoroquinolone group. In a propensity-adjusted analysis, fluoroquinolone use was an independent factor associated with 14-day survival. After stratification using the APACHE II score, treatment with fluoroquinolone was associated with 14-day survival, but did not reach statistical significance in both groups with greater and lesser severity. Therefore, fluoroquinolone is a suitable antimicrobial agent for treating E. meningoseptica bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Cross Infection; Female; Flavobacteriaceae Infections; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; China; Chromatography, Liquid; Cross Infection; Female; Humans; Linear Models; Male; Minocycline; Pneumonia, Bacterial; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Tigecycline

Pneumonia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KP) are increasingly encountered in hospitals worldwide, causing high mortality due to lack of treatment options. The goal of this study was to assess the efficacy of tigecycline and minocycline for CP-KP hospital-acquired pneumonia (HAP) by using Monte Carlo simulation.. A total of 164 non-duplicated CP-KP strains were collected from sputum or blood in patients with HAP. The MICs for antimicrobials were determined by the agar dilution method. A 10,000-patient Monte Carlo Simulation based on a PK/PD model incorporating the MICs and population pharmacokinetic parameters were conducted to calculate probability of target attainment (PTA) at each MIC value and total cumulative fraction of response (CFR).. The susceptibility rate of tigecycline and minocycline were 79.9% and 41.5%, respectively. At recommended doses, an optimal PTA of 90% was obtained for treating HAP caused by CP-KP with MICs of tigecycline ≤0.5 mg/L or minocycline ≤4 mg/L. The CFR of tigecycline at the recommended dose and double dose (100 mg q12h) were 71.2% and 90.2%, respectively. The CFR of minocycline at recommended dose and double dose (200 mg q12h) was 53.4% and 77.2%, respectively.. The findings of this study suggest that the recommended dose of tigecycline was not effective in HAP caused by CP-KP, and a higher CFR indicating a better clinical efficacy can be gained by doubling the dose (100 mg q12h). minocycline (200 mg q12h) might be a potential alternative of tigecycline to against strains with MICs ≤ 8 mg/L.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Models, Statistical; Monte Carlo Method; Pneumonia, Bacterial; Sputum; Tigecycline

Tigecycline is a third-line therapy for severe Clostridium difficile infection (CDI) in Australasian guidelines. Differences in strain types make it difficult to extrapolate international tigecycline efficacy data with combination or monotherapy to Australian practice, where experience is limited.. To evaluate the efficacy and adverse effects associated with tigecycline combination therapy for severe and severe-complicated CDI in an Australian healthcare setting.. This was a retrospective observational study at a metropolitan university-affiliated hospital. All patients between February 2013 and October 2016 treated with adjunctive intravenous tigecycline for >48 h for severe or severe-complicated CDI were included. Tigecycline was given in addition to oral vancomycin ± intravenous metronidazole. The primary outcome was all-cause mortality at 30 days from start of tigecycline combination therapy. Secondary outcomes included clinical cure, colectomy, adverse events and recurrence rates.. Thirteen patients with median age of 61 years had severe (n = 9) or severe-complicated (n = 4) CDI at tigecycline commencement. In 92% of patients, tigecycline started within 48 h after in-hospital CDI treatment, for median duration of 9 days. All-cause mortality at 30 days was 8% with no mortality in severe CDI and 25% (1/4) in patients with severe-complicated fulminant CDI, comparing favourably with historical rates of 9-38% and 30-80% in similar respective groups. Clinical cure was achieved in 77% of cases. There were no colectomies and one attributable tigecycline adverse reaction.. Tigecycline appears safe and effective as a part of combination therapy in severe CDI, and may be given earlier and for shorter durations than in current guidelines.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Australia; Clostridioides difficile; Clostridium Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Metronidazole; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome; Vancomycin

Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) has become increasingly frequent threat recently, especially in the intensive care unit (ICU). High-dose tigecycline (TGC) regimen is proposed due to the limitation of treatment options. We investigated the efficacy and safety of high-dose TGC combination regimens for treating CRKP BSI. Furthermore, the risk factors for mortality were also determined.This was a single center retrospective cohort study conducted from 2014 to 2016. A total of 40 patients with nosocomial CRKP BSI admitted to the ICU were included; they were classified into two groups according to the treatment regimens with high-dose TGC (HD group) or not (non-HD group). In-hospital mortality rates and microbiologic responses from both groups were reviewed and compared. Besides, the survival and non-survival groups were compared to identify the risk factors of mortality.Twenty-three patients constituted the HD group (high-dosage TGC regimen was administered as 200 mg loading dose followed by 100 mg every 12 h) and 17 patients constituted the non-HD group (standard dose TGC therapy as 100 mg loading dose followed by 50 mg every 12 h and other antibiotics). The in-hospital mortality was 52.2% in the HD group and 76.5% in the non-HD group (P = .117). The Kaplan-Meier test showed significantly longer survival times in the HD group (mean: 83 days vs 28 days; P = .027). Microbiological eradication was observed in 13 patients (56.5%) in the HD group and 6 patients (36.3%) in the non-HD group (P = .184). A smaller fraction of patients in the HD group were subjected to vasoactive therapy (52.2% vs 88.2%; P = .016) compared to the non-HD group. There was no significant difference in the manifestation of adverse effects between the two groups. In the multivariate analysis, multiple organ dysfunction syndrome (MODS), vasoactive therapy, and exposure to carbapenems were regarded as the independent predictors of mortality.A therapeutic regimen consisting of a high dose of TGC was associated with significantly longer survival time and numerically lower mortality in CRKP BSI. Adverse events were not increased with the double dose therapy.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings.. The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains.. Clinical and environmental isolates of A. baumannii were obtained from patients, staff, and environment of an educational hospital in Tehran. Antimicrobial susceptibility testing was carried out using the disk diffusion and E-test methods. Multiplex PCR was performed for detection of OXA-type genes (bla. All the isolates were found to be susceptible to colistin and most of them (77%) were non-susceptible to tigecycline. A majority of the clinical and environmental isolates (97%) were considered as MDR strains and 41% as XDR. In multiplex detection, bla. The present study highlights the circulation of drug-resistant A. baumannii strains in different wards of hospitals principally in intensive care unit (ICU) as a nosocomial pathogen due to unwise managements.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Communicable Diseases, Emerging; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Genotype; Hospitals, Teaching; Humans; Intensive Care Units; Iran; Minocycline; Molecular Typing; Tigecycline

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

Enterobacteriaceae are currently causing the majority of healthcare-associated infections (HAI) and simultaneously expressing increasing levels of antibiotic resistance. The purpose of this study is to assess the in vitro sensitivity of MDR strains from the family Enterobacteriaceae to tigecycline in relation to their origin from patients hospitalized in intensive care units (ICUs) and non-ICUs.. The study involved 156 clinically significant strains of the Enterobacteriaceae family isolated from patients with complicated intraabdominal infections (cIAIs) and/or complicated skin and skin structure infections (cSSSIs) hospitalized in ICUs and other surgical departments. Tigecycline MICs were determined by Etest.. The highest percentage of tigecycline non-susceptible (intermediate + resistant strains) in vitro strains among the Enterobacteriaceae species were observed for Serratia spp. 77.3%, followed by Citrobacter spp. (76.9%) and Enterobacter spp. (70%); whereas K. pneumoniae and E. coli showed 73-73.8% tigecycline susceptibility rates.. Tigecycline demonstrates a high level of antimicrobial in vitro activity when tested against E. coli and K. pneumoniae, even those with the ESBL-phenotype. Tigecycline retained activity against merely 22-30% of Enterobacter, Citrobacter and Serratia genera.

Topics: Anti-Bacterial Agents; Cross Infection; Enterobacteriaceae; Humans; Intensive Care Units; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Tigecycline

In recent years, Klebsiella pneumoniae has emerged as a leading cause of nosocomial infection owing to the rising prevalence of multidrug-resistant strains, particularly carbapenem-resistant isolates. In this study, the complete genome sequence of carbapenem-resistant K. pneumoniae SWU01 was determined.. Antimicrobial susceptibilities and hypermucoviscous phenotype were determined by the disk diffusion method and positive string test, respectively. Multilocus sequence typing (MLST) was performed using the K. pneumoniae MLST database, and capsular serotype was analysed using the BIGSdb-Kp database with the nucleotide sequence of the variable region (CD1-VR2-CD2) of wzc. The complete genome sequence was obtained via the PacBio RS II platform, and antimicrobial resistance genes were identified using ResFinder 2.1.. SWU01 was resistant to all antibiotics tested except polymyxin B and minocycline. This strain showed a hypermucoviscous phenotype with serotype K47 belonging to the ST11 clone. The complete genome consists of a 5536506-bp circular chromosome and a 162552-bp plasmid, with a G+C content of 57.4%. A total of 5537 protein-coding sequences, 85 tRNAs, 25 rRNAs, 12 non-coding RNA genes and 157 pseudogenes were identified in the genome. Thirteen acquired antibiotic resistance genes were detected (eight in the chromosome and five in the plasmid).. Here we present the first whole-genome sequence of a carbapenem-resistant hypermucoviscous K. pneumoniae isolate SWU01 with capsular serotype K47 belonging to ST11 from a patient in China, which may serve as a reference sequence for further understanding of the pathogenesis and multidrug resistance mechanisms of this species.

Topics: Anti-Bacterial Agents; Base Composition; Carbapenem-Resistant Enterobacteriaceae; China; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Plasmids; Polymyxin B; RNA, Bacterial; Serogroup; Whole Genome Sequencing

Topics: Anti-Bacterial Agents; Chryseobacterium; Cross Infection; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae Infections; Humans; Male; Middle Aged; Minocycline; Urinary Tract Infections

Raoultella planticola is a gram-negative bacterium that rarely causes diseases in humans. Here, we present a case of hospital-acquired pneumonia caused by R. planticola that likely originated in the gastrointestinal tract. To the best of our knowledge, this is the second report describing the detection of the gene New Delhi Metallo-β-lactamase-1 (bla

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Gene Expression; Humans; Levofloxacin; Male; Minocycline; Plasmids; Polymerase Chain Reaction; Sputum; Tigecycline; Treatment Outcome

Various transmission routes contribute to spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized patients. Patients with readmissions during which CRKP is again isolated ("CRKP readmission") potentially contribute to transmission of CRKP.. To evaluate CRKP readmissions in the Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKLe).. Cohort study from December 24, 2011, through July 1, 2013.. Multicenter consortium of acute care hospitals in the Great Lakes region.. All patients who were discharged alive during the study period were included. Each patient was included only once at the time of the first CRKP-positive culture.. All readmissions within 90 days of discharge from the index hospitalization during which CRKP was again found were analyzed. Risk factors for CRKP readmission were evaluated in multivariable models.. Fifty-six (20%) of 287 patients who were discharged alive had a CRKP readmission. History of malignancy was associated with CRKP readmission (adjusted odds ratio [adjusted OR], 3.00 [95% CI, 1.32-6.65], P<.01). During the index hospitalization, 160 patients (56%) received antibiotic treatment against CRKP; the choice of regimen was associated with CRKP readmission (P=.02). Receipt of tigecycline-based therapy (adjusted OR, 5.13 [95% CI, 1.72-17.44], using aminoglycoside-based therapy as a reference in those treated with anti-CRKP antibiotics) was associated with CRKP readmission.. Hospitalized patients with CRKP-specifically those with a history of malignancy-are at high risk of readmission with recurrent CRKP infection or colonization. Treatment during the index hospitalization with a tigecycline-based regimen increases this risk.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Case-Control Studies; Cross Infection; Female; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Longitudinal Studies; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multivariate Analysis; Odds Ratio; Patient Readmission; Prospective Studies; Risk Factors; Tigecycline; United States

Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for several infections in immunocompromised patients. To characterize the antimicrobial resistance and virulence potential of this microorganism in a Brazilian hospital, a total of 936 samples were collected from a nosocomial environment and medical devices, and 100 isolates from clinical specimens were obtained in the same hospital. S. maltophilia was found in 3% of the samples collected, especially in bed rails from hospital rooms. The smf-1 gene was detected in 23% and 42% of the clinical and hospital environment isolates, respectively, and almost all (96.8%) isolates that harbored smf-1 were able to form biofilm. All isolates were susceptible to minocycline and chloramphenicol, and the majority of isolates were susceptible to levofloxacin. High resistance to ceftazidime was detected in both groups of isolates. Resistance to trimethoprim-sulfamethoxazole (TMP/SMX) was found in 14.8% of the isolates. All TMP/SMX-resistant isolates presented class 1 integron and sul1 gene, and 47.4% of them also harbored the sul2 gene, which was inserted into a 7.3 kb plasmid. Genetic relatedness among the isolates was evaluated by enterobacterial repetitive intergenic consensus-PCR, and eight genetic patterns were identified. One pattern comprised 54.7% of isolates and was spread among clinical and environmental (furniture and medical devices) sources. The presence of S. maltophilia in the hospital environment indicates that it can act as a reservoir of this microorganism. In addition, hospital isolates resistant to TMP/SMX showed that the genetic determinants were present in mobile elements, which can constitute great concern, as it may indicate a tendency to spread.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Biofilms; Brazil; Ceftazidime; Chloramphenicol; Cross Infection; Drug Resistance, Bacterial; Fomites; Gene Expression Regulation, Bacterial; Genes, Bacterial; Gram-Negative Bacterial Infections; Hospitals; Humans; Integrons; Levofloxacin; Minocycline; Phylogeny; Plasmids; Polymerase Chain Reaction; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Tigecycline has a broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains. However, some Gram-negative bacteria are intrinsically resistant or have reduced susceptibility to tigecycline. We performed a prospective, observational study of 43 patients who received tigecycline as the treatment for serious infections due to MDR Gram-negative microorganisms, to evaluate superinfections. In 60.5% of our patients, tigecycline-resistant (T-R) Gram-negative microorganisms were isolated, representing superinfection in 37.2% and colonization in 23.5%. Pseudomonas aeruginosa was the predominant pathogen (48.4%) followed by Providencia stuartii, Proteus mirabilis and Stenotrophomonas maltophilia. Median time elapsed between tigecycline prescription and isolation of T-R pathogens was 7 days. The 16 superinfections consisted of ventilator-associated pneumonias (43.75%), catheter-related bloodstream infections (37.5%), intra-abdominal infections (12.5%) and urinary tract infection (6.25%). Attributed mortality to superinfections was 31.25%. The comparison of various potential risk factors for isolation of T-R microorganisms did not reveal statistically significant results.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Risk Factors; Superinfection; Tigecycline

Colonization, infection, and clonal dissemination of vancomycin-resistant enterococcus (VRE) have been reported in the literature. We aimed to investigate the incidence rate of VRE acquisition and route of transmission of VRE within the medical intensive care unit (ICU) to prove whether subclinical transmission occurs in medical ICUs.. Between March 1, 2012 and September 30, 2013, rectal cultures were obtained from all inpatients on admission and after admission to medical ICU. Strain types of VRE were determined by both multilocus sequence typing and pulsed-field gel electrophoresis.. A total of 66 of the 405 rectal swab surveillance cultures obtained from 46 inpatients were positive for VRE, among which 27 inpatients were culture-positive for VRE on admission to medical ICU, and 19 inpatients were initially culture-negative but converted to culture-positive after admission. All isolates carried vanA gene consisting of 51 Enterococcus gallinarum, 13 Enterococcus faecium, and two Eenterococcus casseliflavus. Of the 51 E. gallinarum isolates, 40 were type ST 341, seven were ST 252, two were ST 78, and two were ST 64. The Enterococcus spp., MLST and PFGE subtypes were almost similar among these two groups of inpatients. Linezolid and tigecycline were most active against VRE in vitro.. Subclinical VRE cross transmission may occur in ICU. Active surveillance and maximal barrier precautions of VRE are required at ICU with high colonization rate of VRE and shall be beneficial.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Cross Infection; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Infection Control; Intensive Care Units; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multilocus Sequence Typing; Taiwan; Tigecycline; Vancomycin; Vancomycin Resistance; Vancomycin-Resistant Enterococci

Tigecycline (Tgc) is considered a last-resort antibiotic for the treatment of multi-drug resistant bacteria. To study Tgc resistance development in the important nosocomial pathogen Acinetobacter baumannii, we adopted six clinical isolates from three patients undergoing antibiotic treatment, and bacterial genomic sequences and seven strand-specific transcriptomes were studied. Interestingly, the Tgc-intermediate 2015ZJAB1 only differed from Tgc-resistant 2015ZJAB2 in an SNP-clustered region including OprD, a sugar-type MFS permease, and a LuxR-type transcriptional regulator. Surprisingly, an almost identical region was found in 2015ZJAB3, which supports the possibility of a homologous recombination event that increased Tgc resistance. Furthermore, comparative transcriptomic analysis identified significantly regulated genes associated with Tgc resistance, which was verified using qRT-PCR. Three enriched COG categories included amino acid transport and metabolism, transcription, and inorganic ion transport and metabolism. KEGG analysis revealed common features under Tgc conditions, including up regulated benzoate degradation and a less active TCA cycle. This may be related to selective antimicrobial pressure in the environment and adaptation by lowering metabolism. This study provides the first report of an in vivo evolutionary process that included a putative homologous recombination event conferring Tgc resistance in clinical A. baumannii isolates in which transcriptome analysis revealed resistance-conferring genes and related metabolism characteristics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Benzoates; Biological Transport; Citric Acid Cycle; Cross Infection; Evolution, Molecular; Gene Expression Regulation, Bacterial; Homologous Recombination; Humans; Membrane Transport Proteins; Minocycline; Phylogeny; Porins; Repressor Proteins; Tetracycline Resistance; Tigecycline; Trans-Activators; Transcriptome

Multidrug-resistant bacterial pathogens are becoming a significant problem worldwide. Acinetobacter baumannii and Pseudomonas aeruginosa are problematic multidrug-resistant pathogens. This multicenter study in Vietnam determined the level of resistance to antimicrobial agents used to treat A baumannii and P aeruginosa infections in this country.. Five medical centers in Vietnam provided 529 P aeruginosa and 971 Acinetobacter species (904 A baumannii) isolates from patients with hospital-acquired or ventilator-associated pneumonia from 2012 to 2014. A central laboratory verified identification of the isolates and performed susceptibility testing using Clinical and Laboratory Standards Institute methods.. Resistance to cephalosporins, β-lactam/β-lactamase inhibitors, carbapenems, and fluoroquinolones was >90% against A baumannii. Aminoglycosides had only slightly better activity, with amikacin resistance >80%. Only colistin (MIC90, ≤0.25 mg/L) and tigecycline (MIC90, 4 mg/L) had appreciable activity against A baumannii. Similar activity was observed among the β-lactams tested against P aeruginosa. Cefepime demonstrated the highest activity (60.1% susceptible), which was similar to doripenem (58.6% susceptible), the most active carbapenem tested. Amikacin was the most active aminoglycoside tested against P aeruginosa, with susceptibility of 81.7% compared with tobramycin (58.0%) and gentamicin (56.5%). Fluoroquinolones had limited activity against P aeruginosa with susceptibility to ciprofloxacin (55.0%). All P aeruginosa isolates had colistin MIC values ≤2 mg/L.. The data from this 3-year longitudinal study in Vietnam demonstrate that 2 of the most common nonfermentative gram-negative pathogens associated with hospital-acquired and ventilator-associated pneumonia are significantly resistant to most of the available treatment options and require combination therapies unless new antimicrobial agents become available.

Topics: Acinetobacter baumannii; Amikacin; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Cross Infection; Doripenem; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Gentamicins; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Tigecycline; Vietnam

Topics: Anti-Bacterial Agents; Child; Cross Infection; Drug Resistance, Bacterial; Enterococcus faecium; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests; Minocycline; Tigecycline

For surgeons the early identification of patients with clostridium difficile infections (CDI) is important, because the incidence and virulence of this potentially life-threatening disease are increasing.. The aim of this study was to describe the frequency of CDI among surgical patients, to analyze which treatment was successful and to define which factors were associated with mortality.. A retrospective analysis of patients with CDI was performed.. From January 2004 to June 2012 the overall incidence of CDI among all departments at the St. Josef Hospital, Ruhr University Bochum was 0.6 % (1669 out of 301,919 patients). In 2004 the number of surgical patients with CDI was 1 which increased to 41 in 2011. Before the diagnosis of CDI was made 84 % (151 out of 179) of patients had received an antibiotic treatment. Conservative management of CDI was performed with metronidazole in 75 % (134 out of 179), 60 % (107 out of 179) received vancomycin, while 44 % (79 out of 179) received a combination of metronidazole and vancomycin, tygecycline or fidaxomidin. The overall mortality was 7 % (12 out of 179). There was a significant association with mortality for patients with sepsis, readmission to the intensive care unit (ICU), requirement for vasopressor therapy and intubation with mechanical ventilation. In 4 % of patients (7 out of 179) colectomy was carried out. Despite maximum intensive care management, 86 % (6 out of 7) of patients who underwent colectomy ultimately died.. Although conservative management is successful for most patients with CDI, the mortality is high for patients who require intensive care management secondary to CDI. Mortality after colectomy for CDI is almost 100 %, mostly because the operation is usually only performed as a last resort in patients with sepsis. The most important risk factor for CDI is a prior antibiotic therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Cohort Studies; Cross Infection; Cross-Sectional Studies; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Fidaxomicin; Germany; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Metronidazole; Middle Aged; Minocycline; Patient Readmission; Retrospective Studies; Survival Rate; Tigecycline; Vancomycin; Young Adult

Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for serious human infections. This study was carried out to determine antibiotic susceptibility, resistance mechanisms (integrons, sul1 and sul2), and genetic relatedness (Enterobacterial Repetitive Intergenic Consensus [ERIC]-PCR) among 106 clinical isolates of S. maltophilia from India. Twenty-four (22.6%) of S. maltophilia isolates exhibited resistance to mainstay antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). Except for 2 isolates which contained both TMP-SMX resistance determinants sul1 and sul2 genes, all other 22 TMP-SMX-resistant isolates carried either sul1 (10 isolates) or sul2 (12 isolates) genes. Class 1 integrons were present in 8.5% (9 out of 106) of S. maltophilia isolates, and only 5 out of these isolates were TMP-SMX resistant and positive for sul1 gene. The same isolates also carried resistance cassettes containing qac/smr gene. Minocycline and levofloxacin exhibited the maximum in vitro activity against S. maltophilia. ERIC-PCR revealed high diversity among S. maltophilia isolates. The present study demonstrated high (22.4%) TMP-SMX resistance in clinical isolates of S. maltophilia from India. TMP-SMX-resistant isolates carried relatively higher percentage of sul2 gene than sul1 gene as against the reported literature. Majority (58.3%) of sul1 gene positive were not associated with class 1 integrase gene.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; India; Integrons; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Polymerase Chain Reaction; Stenotrophomonas maltophilia; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

We describe an outbreak caused by KPC-2- and IMP-10-producing Serratia marcescens isolates in a Brazilian teaching hospital. Tigecycline was the only active antimicrobial agent tested. The blaIMP-10 gene was located in a new class 1 integron, named In990, carried by a nonconjugative plasmid, in contrast to blaKPC-2.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Brazil; Carbapenems; Child, Preschool; Cross Infection; Disease Outbreaks; DNA, Bacterial; Female; Genes, Bacterial; Hospitals, Teaching; Humans; Infant; Integrons; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Molecular Sequence Data; Plasmids; Sequence Analysis, DNA; Serratia Infections; Serratia marcescens; Tigecycline

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

Topics: Aged; Anti-Bacterial Agents; Case-Control Studies; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Proteus; Pseudomonas; Retrospective Studies; Risk Factors; Tigecycline

In 2010 the Hellenic center for disease control and prevention launched the "Prokroustes" nationwide action plan to tackle the increasing rates of carbapenem resistance among gram-negative nosocomial pathogens. In the present report, data from a Greek tertiary-care hospital are presented three years after the adoption of the infection control measures. Carbapenem resistance rates have been contained for Klebsiella pneumoniae and Acinetobacter baumannii but not for Pseudomonas aeruginosa. More worryingly, in accordance with their overuse against carbapenem-resistant bacteria, resistance rates to colistin and tigecycline have risen significantly.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Containment of Biohazards; Cross Infection; Drug Resistance, Multiple, Bacterial; Gentamicins; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tigecycline

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia.. A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens.. The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily.. The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.

Topics: Adult; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cross Infection; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Moxifloxacin; Pneumonia; Sputum; Stenotrophomonas maltophilia; Tigecycline

Coagulase negative Staphylococcus continues generating interest in critically ill patients, due to their infections in extended admissions, in instrumented patients and due to their described multidrug resistance, which include glycopeptide heterorresistance and the increase in oxazolidinone resistance. Ceftaroline is a new cephalosporin with activity against resistant gram-positives, which, being betalactam, may provide adequate safety profile in the critical ill patient. The aim of this study was to determine the activity of ceftaroline and other antimicrobial agents against methicillin and linezolid-resistant Staphylococcus epidermidis.. We studied susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with clinical significance from an Intensive Care Unit, using E-test.. All strains were susceptible to the four antimicrobial agents, regardless of the level of resistance to linezolid.. Ceftaroline could be an alternative in the treatment of methicillin and linezolid-resistant S. epidermidis infections in critically ill patients.

Topics: Anti-Bacterial Agents; Bacteremia; Body Fluids; Catheter-Related Infections; Ceftaroline; Cephalosporins; Critical Care; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Exudates and Transudates; Humans; Linezolid; Methicillin; Minocycline; Staphylococcal Infections; Staphylococcus epidermidis; Tigecycline; Vancomycin

To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013.. Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation.. Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to β-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains.. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, β-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Cephalosporins; China; Cross Infection; Hospitals, Teaching; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline; Vancomycin

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 50 patients between July 2011 and July 2012 at the University Hospital A Coruña (NW Spain). These multidrug-resistant isolates, which belonged to a single clone, remained only susceptible to tigecycline, minocycline, and colistin and produced the carbapenem-hydrolyzing oxacillinase, OXA-23. This is the first reported outbreak of OXA-23-producing A. baumannii isolates in Spain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Gene Expression; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Spain; Survival Analysis; Tigecycline

The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin-resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings. Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32 μg/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study. Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively. In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin-resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1 μg/mL.

Topics: Acetamides; Anti-Bacterial Agents; Cephalosporins; Computer Simulation; Cross Infection; Daptomycin; Dose-Response Relationship, Drug; Humans; Intensive Care Units; Linezolid; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Minocycline; Models, Biological; Monte Carlo Method; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Vancomycin

Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia.. Adult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates.. Of 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC50 and MIC90 of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality.. The high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Retrospective Studies; Taiwan; Tigecycline

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pneumonia, Staphylococcal; Tigecycline; Vancomycin; Virginiamycin

Bacterial infections because of multidrug-resistant (MDR) bacteria are spreading worldwide. In patients with advanced liver cirrhosis, healthcare-acquired and hospital-acquired infections are common and are frequently sustained by MDR bacteria. In these settings, tigecycline, a new antibiotic, has been shown to be useful in the treatment of MDR bacteria, and it has been proposed for the treatment of hospital-acquired infections in patients with cirrhosis. Nevertheless, poor data exist on the safety profile of tigecycline in patients with cirrhosis. Here, an experience is reported in a female patient with advanced liver cirrhosis, who developed sepsis by an MDR Stenotrophomonas maltophilia and was treated with tigecycline. She experienced life-threatening side effects consisting of severe coagulopathy with hypofibrinogenaemia and subsequent gastrointestinal haemorrhage. The side effect disappeared after the withdrawal of tigecycline. Therefore, a strict monitoring of coagulation parameters in patients with cirrhosis treated with tigecycline is recommended.

Topics: Adult; Afibrinogenemia; Anti-Bacterial Agents; Blood Coagulation Disorders; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Liver Cirrhosis; Minocycline; Opportunistic Infections; Stenotrophomonas maltophilia; Tigecycline

Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy.. Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR.. CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum β-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified.. CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; Anti-Bacterial Agents; C-Reactive Protein; Carbapenems; Cefoperazone; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Sulbactam; Thienamycins

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 μ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Pneumonia, Bacterial; Tigecycline

This prospective observational study aimed at describing prescription patterns of tigecycline and patient outcomes in 26 French intensive care units (ICU).. Data of consecutive cases of adult patients treated with tigecycline were collected from the initiation until 7 days after the end of treatment. Response to treatment was classified as success, failure or undetermined and analyses were presented according to severity (SOFA score <7 or ≥7). Survival was recorded at 28 days.. A total of 156 patients were included (64% male, age 60 ± 15 years). At inclusion, 53% had a SOFA score ≥7; 93% had received prior anti-infective agents. Tigecycline was given as first-line treatment in 47% of patients, mostly in combination (67%), for intra-abdominal (IAI 56%), skin and soft tissue (SSTI 19%) or other infections. A total of 76% of the treated infections were hospital-acquired. Bacteraemia was reported in 12% of patients. Median treatment duration was 9 days. Tigecycline was prematurely stopped in 42% patients. The global success rate was 60% at the end of treatment, and significantly higher with treatment duration more than 9 days (76 vs. 47%, P < 0.001). Success rate was 65% for patients alive at the end of treatment. Success rates tended to decrease with illness severity, immunosuppression, bacteraemia and obesity. Survival rate at day 28 was 85% in the whole cohort and significantly higher in the less severely ill patients (P < 0.001).. Tigecycline success rates appear comparable to those reported in clinical studies in ICU with severe infections. Tigecycline could be an alternative in ICU patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Critical Illness; Cross Infection; Drug Therapy, Combination; Female; France; Hospital Mortality; Humans; Immunocompromised Host; Infections; Intensive Care Units; Male; Middle Aged; Minocycline; Multivariate Analysis; Obesity; Patient Outcome Assessment; Prospective Studies; Severity of Illness Index; Tigecycline; Young Adult

Acinetobacter baumannii is an important nosocomial pathogen able to cause severe infections in an intensive care unit (ICU). However, there is a lack of analysis regarding the epidemiology and resistance of A. baumannii in respiratory department ICUs. In this study, clinical isolates were collected from the respiratory department ICU of Southwest Hospital from January 2009 to December 2010, and the social and demographic information of the patients from whom the isolates were taken was obtained from the Southwest Hospital information system. The minimal inhibitory concentration (MIC) of the isolates was determined by the agar dilution method. The carbapenemase-encoding resistance genes of these isolates were amplified using PCR. The clonal relationship of isolates was analyzed by pulsed-field gel electrophoresis (PFGE). Forty-six isolates were collected from the respiratory department ICU, and the antibiotics minocycline and quinolone had higher drug sensitivity against these isolates. The OXA-51, OXA-23, and IMP-4 genes were present at rates of 100% (46/46), 67.4% (31/46), and 41.3% (19/46), respectively. Forty-six isolates had 12 different PFGE genotypes. The results above suggested that the hospital environment and patients contributed to nosocomial infections, and the spread of resistance genes in the hospital was common.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Child, Preschool; China; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Infant; Infant, Newborn; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Quinolones; Young Adult

For an antibacterial agent to be considered for clinical studies in nosocomial pneumonia (NP), it should be active in the presence of pulmonary surfactant. Furthermore, owing to the common practice of treating such infections with more than one antibacterial agent, it should be free of antagonistic interactions with agents of other classes. The aim of this study was to demonstrate the effect of pulmonary surfactant on the activity of ceftazidime and ceftazidime-avibactam and to determine the interaction (if any) of ceftazidime-avibactam and six antimicrobial agents common in the treatment of NP. Minimum inhibitory concentration (MIC) determination for ceftazidime and ceftazidime-avibactam was performed with and without the presence of four concentrations of bovine pulmonary surfactant, and a chequerboard assay was used to determine any interaction between ceftazidime and ceftazidime-avibactam with tobramycin, levofloxacin, linezolid, vancomycin, tigecycline and colistin. Here we report that the in vitro antimicrobial activity of ceftazidime-avibactam against β-lactamase-producing Gram-negative bacteria remained unaltered in the presence of pulmonary surfactant at concentrations that antagonised the antimicrobial activity of daptomycin. Furthermore, in chequerboard interaction studies, an absence of antagonism was demonstrated between ceftazidime-avibactam and six antimicrobial agents of different classes when tested against aerobic species frequently isolated from NP. The results support the further investigation of ceftazidime-avibactam as a potential treatment for NP caused by susceptible bacteria.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Ceftazidime; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Pulmonary Surfactants; Tigecycline; Tobramycin

Clinical information on tigecycline use in serious nosocomial infections is limited, and the efficacy is uncertain. The aim of this retrospective study was to assess the utilization pattern and the effectiveness of tigecycline in a tertiary medical center in Taiwan.. A retrospective study of the clinical and microbiological outcome of all patients treated with tigecycline for at least 72 hours over a 2-year period was conducted in a 730-bed teaching hospital.. Data from 133 patients with 149 cases of nosocomial infection were analyzed in this assessment. The mean APACHE II score at the initiation of tigecycline therapy was 22.5 ± 8.8, and the mean duration of treatment was 11.4 ± 5.6 days. Pneumonia was the most frequently diagnosed clinical indication for tigecycline use (113 cases, 76%). An overall positive clinical outcome was observed in 75 cases (50%). Multidrug-resistant Acinetobacter baumannii (MDRAB) is the most common organism for tigecycline therapy (n = 59), with a positive clinical outcome of 38% in tigecycline monotherapy, 66% in dualtherapy, and 17% in triple-therapy (p = 0.031). The most commonly used combining agents with tigecycline to treat MDRAB infections were intravenous colistin, inhaled colistin, and cepoferazone/sulbactam, with positive clinical outcome rates of 53%, 100%, and 80%, respectively. Admission to intensive care unit was identified as a predictive factor for negative clinical outcome.. Our pneumonia-dominated study population demonstrated a lower clinical improvement rate of tigecycline compared to previous published data. Tigecycline monotherapy is not recommended for MDRAB infection, but colistin or cephoperazone/ sulbactam combined with tigecycline seemed to yield a good clinical outcome for MDRAB infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA) is a strain of MRSA that can cause infections in patients in the community, in which these patients had no previous risk factors for MRSA infection and the patient received 72 hours prior to infection when admitted to hospital. This study aims to determine and compare the characteristics of epidemiological, clinical, and molecular biology of CA-MRSA with HA-MRSA.. A total of 11 clinical strains of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Stapylococcus aureus (MSSA) were collected from 2 hospitals in Jakarta, Indonesia in 2012. SCCmec typing was performed by multiplex polymerase chain reaction (PCR) and the presence of six genes (vraR, vraG, vraA, vraF,fruA, and fruB) associated with vancomycin resistance was examined by simple PCR analysis.. We found three strains of community-acquired MRSA with SCCmec type II and one strain of hospital-acquired MRSA with SCCmec type IV. The other seven strains did not contain mecA genes and SCCmec. Plasmid pUB110 was found in one strain of community-acquired MRSA and two strains of hospital-acquired MRSA. vraA genes were present in 9 of the 11 strains, vraF in 4, vraG in 5, and vraR in 4. Note worthily, three quarters of strains without pUB110 contained vraR and vraF, and 70% contained vraA, whereas 60% of strains with pUB110 contained vraG.. Based on these results, we should be concerned about the possibility of transition from MRSA strains sensitive to vancomycin in VISA strains of MRSA strains obtained in clinical trials. But first we need to look the existence of natural VISA or hVISA among these MRSA strains.

Topics: Acetamides; Amikacin; Clindamycin; Community-Acquired Infections; Cross Infection; DNA Primers; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Indonesia; Linezolid; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Plasmids; Polymerase Chain Reaction; Species Specificity; Teicoplanin; Tigecycline; Time Factors; Vancomycin

Intra-abdominal infection (IAI) is a frequent complication found in surgical intensive care unit (SICU) and continues to be associated with considerable mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad spectrum of activity against a wide range of bacteria commonly found in IAI. This observational retrospective study aimed to describe the experience with tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23 consecutive patients admitted to SICU with serious nococomial IAI who had received empirical treatment with tigecycline. In all cases, IAI was diagnosed via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed septic shock. Oncological disease was the most common comorbidity (60%). The mean Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis was 57.5±14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus spp. (30.4%, respectively). All but one patient received tigecycline in combination (95.7%), particularly with fluconazole (52.2%), followed by piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered adequate in 95%. The mean duration of treatment was 8.5±4.5 days. A favorable response was achieved in 78%. Failure of the antibiotic therapy was not observed in any patient. None of the patients discontinued tigecycline due to adverse reactions. SICU mortality was 13%, with no deaths attributable to tigecycline. These findings suggest that tigecycline combination therapy is an effective and well tolerated empirical treatment of serious nosocomial IAI in the SICU.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Critical Care; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Postoperative Complications; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

Tigecycline (TG) has been shown to be active in vitro against Acinetobacter baumannii, although data on the clinical efficacy of TG alone or in combination for the treatment of infections due to multidrug-resistant A. baumannii (MDRAB) remain limited. The purpose of this study was to investigate the clinical outcomes of patients with healthcare-associated infections (HAIs) caused by MDRAB who were treated with imipenem/cilastatin and sulbactam, and TG alone or in combination with other antibiotics. A total of 386 patients with HAIs caused by MDRAB were retrospectively analyzed and grouped into TG and non-TG groups, depending on whether they received TG treatment. Of the 266 patients in the TG group, 108 were treated with TG alone and 158 were treated with TG in combination with ceftazidime, ceftriaxone, piperacillin/tazobactam, or a carbapenem. All 120 patients in the non-TG group were treated with imipenem/cilastatin and sulbactam. The primary outcome measure was 30-day mortality after TG treatment and the secondary outcome was clinical outcome. There were no significant differences in survival rates between the two groups. However, the rate of unfavorable outcome was significantly lower (p < 0.05) among patients in the TG group than among patients in the non-TG group. The most significant predictor of unfavorable outcome was sepsis, whereas TG treatment and microbial eradication were the most significant predictors of favorable outcomes. Our study represents the largest study of patients with MDRAB infection treated with TG and expands our understanding of the role of TG therapy alone or in combination with other agents for the treatment of HAI caused by MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Cilastatin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Minocycline; Piperacillin; Sulbactam; Tigecycline; Treatment Outcome

Nosocomial infection caused by carbapenem-resistant Acinetobacter baumannii is a worldwide problem and treatment options remain controversial. This study investigated the in vitro effect of various antibiotic combinations against carbapenem-resistant A. baumannii strains.. Antibiotic susceptibility of A. baumannii strains was analysed. In vitro synergistic efficacy of colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam was tested against carbapenem-resistant A. baumannii strains. Synergy studies were performed using an eplisometer test-strip method.. Of the 50 carbapenem-resistant A. baumannii strains tested, 96% were susceptible to colistin and 64% were susceptible to tigecycline. Colistin-tigecycline, colistin-cefoperazone/sulbactam and colistin-piperacillin/tazobactam combinations were found to have synergistic effects against six (12%), two (4%), and one (2%), respectively, of the strains tested.. Colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam revealed synergistic effects in some carbapenem-resistant A. baumannii strains. These results, together with the shortage of treatment options and the risk of developing resistance to colistin, suggest that clinicians should use colistin combined with other antibiotics or β-lactamase inhibitors when treating carbapenem-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Tigecycline

The management of infections due to A. baumannii is difficult because of rapidly developing resistance, however, tigecycline, a glycylcycline antimicrobial, is in use for several years. In the present study, it was aimed to determine the susceptibility rates of A. baumannii to tigecycline. A total of 90 A. baumanni isolates were tested using three methods such as disk diffusion, broth microdilution, and E-test. The MIC50 and MIC90 values and the MIC range were found as 2 µg/ml, 4 µg/ml, and 0.1-8 µg/ml by microdilution; and 2 µg/ml, 6 µg/ml, and 0.1-12 µg/ml by E-test, respectively. There were a few major errors as well as the minor rates were all high as between 35.7%-46.7%. The accuracy rates between the methods were low as 53.3% (48/90) between disk diffusion and E-test, 51.1% (46/90) between disk diffusion and microdilution, and 60.0% (54/90) between E-test and microdilution. In the ROC curve analysis, an inhibition zone diameter of susceptibility breakpoint of 21.5 mm had sensitivity between 68.8%-88.9%; specificity between 81.9%-87.9%; and accuracy between 80.0%-83.33%. An analysis based on EUCAST's non-species breakpoints, the MIC tests showed higher accuracy with a rate of 96.7%, however, performance of disk diffusion got worse as lower than 25%. In conclusion, we showed that the reliability of the methods even did not remain as high as the past. Our study presented that none of three methods revealed reliable results in determination of susceptibility of A. baumanni to tigecycline, so the clinical response should be followed up carefully in such cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reproducibility of Results; Tigecycline

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Minocycline; Molecular Sequence Data; Tigecycline

Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant patient suffering from recurrent urosepsis over a period of 4 months. Imipenem resistance was detected after imipenem-ertapenem therapy. When treatment was switched to tigecycline the K. pneumoniae developed resistance to tigecycline (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo-beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase chain reaction and sequencing analysis were employed for identification of bla genes and mapping of the integron carrying the MBL gene. The nine isolates were clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing with imipenem and EDTA. The five isolates harboured the bla(VIM-1) gene. Three isolates showed increased tigecycline MICs (4-8 mg/L). Serial blood cultures obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed concurrent imipenem and tigecycline resistance. The patient had a persistent urinary tract infection and recurrent bacteraemia caused by a mixed population of Klebesiella pneumoniae isolates adapting to the selective pressure of antimicrobial therapy at the time. The present study is a worrisome example of what could happen when an immunocompromised host is subjected to the pressures of antimicrobial therapy. In addition, we report the first treatment-emergent MIC increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; beta-Lactamases; Carbapenems; Chromosome Mapping; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Sequence Analysis, DNA; Tigecycline; Urinary Tract Infections

Acinetobacter species are well-known causes of health care-associated infections. The longitudinal epidemiology of this species in the hospital setting is poorly understood. A sudden, persistent increase in multidrug-resistant (MDR) A baumannii infections occurred beginning in June 2006 at Temple University Hospital in Philadelphia. An analysis was done to describe the longitudinal molecular epidemiology of MDR A baumannii in a tertiary care hospital.. This was an epidemiologic investigation using repetitive extragenic palindromic-PCR (rep-PCR) of patients with a positive culture for MDR A baumannii admitted to the hospital between February 2006 and January 2010. MDR A baumannii were defined as susceptible only to colistin and/or tigecycline.. The incidence rate of MDR A baumannii rose from 0.36 cases per 1,000 patient-days (pre-epidemic) to 0.86 cases per 1,000 patient-days, due mainly to an increase in the surgical intensive care unit. Enhanced infection control measures were implemented, but waves of MDR A baumannii continued to be documented through routine surveillance. Of 32 strains collected in 2006-2007, a single predominant clone and 2 minor clones accounted for almost all of the cases of MDR A baumannii studied. Of 24 strains collected in 2008-2009, another clone, different from those studied in the earlier period, predominated, and was accompanied by 3 minor variants.. Following an outbreak in the surgical intensive care unit, MDR A baumannii persisted in our institution for a 3-year period despite rigorous infection control measures. An unexpected strain replacement occurred during this period, with the original predominant strain disappearing completely and new minor clones displacing the original minor clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Incidence; Intensive Care Units; Longitudinal Studies; Minocycline; Philadelphia; Polymerase Chain Reaction; Tigecycline

Tigecycline (TGC), an antibiotic belonging to glycylcyclines, is active against Gram-positive bacteria, including multi-resistant bacteria, and most of the Gram-negative bacteria, including extended spectrum β-lactamase-producers (ESBL) and Acinetobacter sp. TGC is not active on Pseudomonas aeruginosa. The microbiological laboratory from the university hospital of Angers participates in the Tigecycline Evaluation and Surveillance Trial (TEST) since 2006. The objective of this study is to evaluate the effectiveness of TGC and of various comparators against nosocomial and community-acquired pathogens. We also evaluated the effectiveness of TGC on a panel of strains isolated between 2006 and 2009 in the university hospital of Angers. Minimum inhibitory concentrations (MIC) were determined using the microdilution method. A total of 760 clinical strains were tested. TGC had a very good activity against Gram-positive bacteria, with 100 % of susceptibility for all the strains tested, irrespective of their resistance profile. Concerning Gram-negative bacteria, TGC was active against 93 % of Enterobacteriaceae, with a MIC 90 not exceeding 2mg/L. Whole of the 20 strains ESBL-producers tested were susceptible to TGC. Acinetobacter sp. were also inhibited at low concentrations of TGC, with a MIC 90 of 1mg/L. These results suggest that TGC can be a useful therapeutic alternative, especially for infections involving multiresistant bacteria.

Topics: Acinetobacter; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; France; Hospitals, University; Humans; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Tigecycline

Topics: Adult; Aged; Anti-Bacterial Agents; Carrier State; Clinical Trials as Topic; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Off-Label Use; Opportunistic Infections; Practice Guidelines as Topic; Salvage Therapy; Soft Tissue Infections; Stenotrophomonas maltophilia; Tigecycline

We investigated the clinical characteristics and outcomes of 43 patients with Acinetobacter junii bacteremia at a 2,500-bed tertiary care center in northern Taiwan. These organisms were confirmed to the species level by an array assay and 16S rRNA gene sequence analysis. The antimicrobial susceptibilities of the 43 A. junii isolates to 13 agents were determined using the agar dilution method. Susceptibility testing for tigecycline was determined using the broth microdilution method. Most of the patients were hospital-acquired (n = 36, 83.7 %) or healthcare facility-related infections (n = 6, 13.9 %), and 55.8 % had impaired immunity. Central venous access devices were present in 35 (81.4 %) patients; among the total of 43 patients with A. junii bacteremia, 8 patients were diagnosed as catheter-related bloodstream infection and 19 patients were diagnosed as catheter-associated bloodstream infection. Shock requiring inotropic agents occurred in 2 patients (4.6 %). Most patients developed bacteremia in general wards (n = 36, 83.7 %). The overall in-hospital mortality rate was low (7 %), despite the low rate of removal of central venous devices, low rate of holding usage of original central venous devices, and high rate of inappropriate antimicrobial regimens. Carbapenems, fluoroquinolones, and amikacin had potent activity (>95 % susceptible rate) against A. junii isolates. Interestingly, 35 % of the A. junii isolates were resistant to colistin. Tigecycline exhibited low minimum inhibitory concentration (MIC) values (range, 0.06-2 μg/ml, MIC(90), 1 μg/ml) against the A. junii isolates.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Carbapenems; Catheter-Related Infections; Central Venous Catheters; Colony Count, Microbial; Cross Infection; Drug Resistance, Bacterial; Female; Hospital Mortality; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Taiwan; Tertiary Care Centers; Tigecycline

Criteria of tigecycline (Tygacil) use for the treatment of surgical site infections in oncologic inpatients were developed. High efficacy of tigecycline in vitro and in vivo against multiresistant hospital strains persistent in the surgical department of the gastrointestinal oncologic division was shown.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Neoplasms; Surgical Wound Infection; Tigecycline

Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Interspersed Repetitive Sequences; Minocycline; Molecular Sequence Data; Sequence Analysis, DNA; Tigecycline

To explore the effects of cefoperazone-sulbactam (C/S) plus minocycline on extensively drug resistant Acinetobacter baumannii (XDRAB) infections in critically ill patients.. For this prospective and single-center trial, a total of 101 patients with infection due to XDRAB received the primary therapy of C/S plus minocycline. Combined use of imipenem-cilastatin was considered when primary therapy failed.. Among them, 77 patients were evaluated. There were 49 males and 28 females with a mean age of (69±20) years. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15±5. Among whom 61 had hospital-acquired pneumonia (n=61), primary bacteremia (n=5), intra-abdominal infection (n=3), skin and soft tissue infection (SSTI) (n=2) and multiple sites infection (n=6). Twenty-three patients had mixed bacterial infections. Combined use of imipenem-cilastatin therapy was administered in 7 patients. The treatment duration was (16±4) days. The outcomes were cure (n=21), marked improvement (n=27), improvement (n=26) and ineffectiveness (n=3). The overall effective rate was 62.3% (48/77) and the microbiological clearance rate 46.8% (36/77). The independent factors of decreased efficacy were underlying co-morbidity of impaired ability for infection control (OR=5.3, P=0.020), prolonged infection (OR=3.8, P=0.029), co-infecting organism (OR=3.5, P=0.032) and septic shock (OR=2.5, P=0.037).. The combined regimen of C/S and minocycline is efficacious in the treatment of infections caused by XDRAB. But it has a lower rate of microbiological eradication.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Cefoperazone; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Sulbactam

Catheters coated with minocycline and rifampin are proven to decrease the rates of central line-associated bloodstream infection; however, it is unclear whether success occurs independent of other infection control precautions. We evaluated the effect of catheters coated with minocycline and rifampin with and without other infection control precautions on our rates of central line-associated bloodstream infection in critically ill patients and on antibiotic resistance throughout the hospital and in the intensive care unit.. Retrospective clinical cohort study conducted during 1999-2006 with an observational laboratory component.. A tertiary university-based cancer center.. All 8009 patients admitted to the medical intensive care unit were subjects for the surveillance of central line-associated bloodstream infection. All Staphylococcus aureus and coagulase-negative staphylococci clinical isolates cultured at our institution during the same period were subjects for laboratory testing.. Using catheters coated with minocycline and rifampin and implementing infection control precautions.. Incidence of central line-associated bloodstream infection in the medical intensive care unit. Change in resistance to tetracycline and rifampin in clinically relevant staphylococcal isolates in the intensive care unit and hospitalwide. During the study period, 9200 catheters coated with minocycline and rifampin were used hospitalwide over a total of 511,520 catheter days. The incidence of central line-associated bloodstream infection per 1000 patient days in the medical intensive care unit significantly and gradually decreased from 8.3 in 1998 to 1.2 in 2006 (p ≤ .001). The resistance of S. aureus and coagulase negative staphylococci clinical isolates to tetracycline or rifampin in the intensive care unit and on a hospitalwide level remained stable or decreased significantly during the same period.. Catheters coated with minocycline and rifampin significantly decreased the incidence of central line-associated bloodstream infection in the medical intensive care unit in a manner that was independent and complementary to the infection control precautions. Although this study strongly suggests an association between catheters coated with minocycline and rifampin use and a decrease in central line-associated bloodstream infection, because of multiple other concurrent interventions, the results should be interpreted cautiously until a prospective study is conducted. Furthermore, long-term use of these devices is not associated with increased resistance of staphylococcal isolates to tetracycline and rifampin in the intensive care unit or throughout the hospital.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Blood-Borne Pathogens; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Chi-Square Distribution; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Humans; Infection Control; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Retrospective Studies; Rifampin; Risk Assessment; Statistics, Nonparametric; Time Factors; Treatment Outcome

Topics: Anti-Infective Agents; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Drug Delivery Systems; Female; Humans; Infection Control; Male; Minocycline; Reference Values; Rifampin

We evaluated the activity of tigecycline against Enterobacteriaceae (9563 isolates) and Acinetobacter spp. (835) with various resistance phenotypes collected from 31 US medical centers in 2005-2009. The isolates were tested for susceptibility by the reference broth microdilution method against tigecycline and various comparators. Among Escherichia coli and Klebsiella spp., 6.8% and 15.4% exhibited an extended-spectrum β-lactamase (ESBL) phenotype, respectively; and 22.2% of Enterobacter spp. strains were ceftazidime-resistant. Tigecycline was active against E. coli [minimum inhibitory concentration (MIC(50/90)), 0.12/0.25 μg/mL; 100.0% susceptible] independent of ESBL phenotype or resistance to other antimicrobials. Among Klebsiella spp., 97.9% of ESBL-producing Klebsiella spp. and 98.2% of imipenem-non-susceptible strains were susceptible to tigecycline (MIC(50/90), 0.5/1 μg/mL for both subsets). Tigecycline was active against Enterobacter spp. (MIC(50/90), 0.25/1 μg/mL; 98.4% susceptible), including ceftazidime-resistant strains (MIC(50/90), 0.5/2 μg/mL; 97.1% susceptible). Tigecycline inhibited 94.4% of Acinetobacter spp. overall (MIC(50/90), 0.5/2 μg/mL) and 86.2% of imipenem-non-susceptible (MIC(50/90), 1/4 μg/mL) strains at ≤2 μg/mL. No trend toward decreased tigecycline activity overtime was observed for any of the organisms or resistant subsets during the study period. These results indicate that tigecycline has sustained potent in vitro activity and a broad spectrum against these clinically important Gram-negative pathogens causing infections in US medical centers, including multidrug-resistant organism subsets.

Topics: Acinetobacter; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; United States

This study assessed the demographics, antimicrobial susceptibility, and molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and health care-associated MRSA (HA-MRSA) in Canadian hospitals between 2007 and 2009. Among 3589 S. aureus, 889 (24.8%) were MRSA; 224 (25.2%) were CA-MRSA genotypes and 644 (72.4%) were HA-MRSA genotypes. The prevalence of CA-MRSA genotypes increased from 19.5% in 2007 to 31.9% in 2009 (P < .001). CMRSA10/USA300 (73.7%) was the predominant CA-MRSA epidemic type; the most common HA-MRSA epidemic type was CMRSA2/USA100/800 (83.5%). CA-MRSA genotypes carried SCCmec type IVa (98.2%) and were largely agr type I (73.2%). Most HA-MRSA genotypes were SCCmec type II (81.2%) and agr type II (83.4%). Panton-Valentine leukocidin was detected in 201/224 (89.7%) CA-MRSA genotypes and 3/644 (0.5%) HA-MRSA genotypes. An increase in vancomycin minimum inhibitory concentration (MIC) was observed in HA-MRSA genotypes overall, with 1.3% (4/305) of strains in 2007 and 4.6% (7/152) in 2009 exhibiting vancomycin MICs of 2 μg/mL. No MRSA resistance occurred with linezolid, daptomycin, or tigecycline. In conclusion, CA-MRSA genotypes represented 25.2% of all MRSA and continue to increase in prevalence in Canadian hospitals.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Toxins; Canada; Child; Child, Preschool; Community-Acquired Infections; Cross Infection; Daptomycin; DNA, Bacterial; Drug Resistance, Bacterial; Exotoxins; Female; Hospitals; Humans; Infant; Leukocidins; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Minocycline; Oxazolidinones; Staphylococcal Infections; Tigecycline; Vancomycin Resistance

Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009.. The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out.. Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy.. Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Infective Agents; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Humans; Infection Control; Intensive Care Units; Italy; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin resistant Staphylococcus aureus (MRSA) are important nosocomial pathogens. This study reports the in vitro activity of tigecycline against 573 and 482 ESBL-producing Enterobacteriaceae and MRSA isolates, respectively. More than 94% of all tested isolates were susceptible to tigecycline; MIC(90) found was 0.25 to 2 mg/L for ESBL-producing Enterobacteriaceae and was 0.125 mg/L for MRSA. Tigecycline demonstrated excellent in vitro activity against a wide spectrum of nosocomial pathogens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mexico; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Tigecycline; Young Adult

The aim of this study was to determine the minimal inhibitory concentration (MIC) values of vancomycin, teicoplanin, tigecycline and linezolid in 100 methicillin-resistant staphylococci [21 methicillin-resistant Staphylococcus aureus (MRSA) and 79 methicillin-resistant coagulase negative staphylococcus (MR-CNS)] isolated as agents of nosocomial infection from patients at Ankara Training and Research Hospital between June 2005-March 2007. The MIC values for vancomycin, teicoplanin, linezolid and tigecycline were tested by E-test method (AB Biodisk, Sweden). For 21 MRSA strains MIC50 and MIC90 values were as follows: vancomycin 0.125 µg/ml and 1 µg/ml; teicoplanin 0.5 µg/ml and 3 µg/ml, linezolid 0.047 µg/ml and 0.19 µg/ml; tigecycline 0.094 µg/ml and 0.5 µg/ml, respectively. For 79 MR-CNS strains MIC50 and MIC90 values were as follows: vancomycin 0.5 µg/ml and 2 µg/ml; teicoplanin 2 µg/ml and 4 µg/ml; linezolid 0.125 µg/ml and 0.25 µg/ml; tigecycline 0.38 µg/ml and 0.5 µg/ml, respectively. No resistance to vancomycin, teicoplanin, tigecycline and linezolid were determined in methicillin-resistant staphylococcus strains isolated from the inpatients in our hospital. Among glycopeptides, MIC50 and MIC90 values of vancomycin were found to be lower than that of teicoplanin.

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Turkey; Vancomycin

The Tigecycline Evaluation and Surveillance Trial (TEST) is a global surveillance study designed to monitor the in vitro activity of the broad-spectrum antimicrobial tigecycline against nosocomial- and community-acquired pathogens. In this study the in vitro activity of tigecycline against 1256 anaerobic pathogens collected across Europe has been compared to the activity of several comparator antibiotics. The pathogens examined in this study included Bacteroides, Prevotella, Anaerococcus, Clostridium, Finegoldia and Peptostreptococcus. Low minimum inhibitory concentration (MIC(90)) values were noted against Gram-positive anaerobes for most agents on the test panel, with the exceptions of cefoxitin and clindamycin. Low MIC(90)s were also reported against Gram-negative isolates for most agents, with the exceptions of clindamycin and, to a lesser degree, piperacillin-tazobactam. The lowest MIC(90)s against both Gram-negative and Gram-positive organisms were typically noted for the carbapenem meropenem and tigecycline. Tigecycline showed the lowest MIC(90) against the key pathogen Clostridium difficile (0.25 mg/l). These in vitro results indicate that tigecycline may be useful in the treatment of infections caused by or involving anaerobic pathogens.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Community-Acquired Infections; Cross Infection; Europe; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Activity of tigecycline against nosocomial secondary peritonitis isolates collected along 18 months in 29 Spanish hospitals was tested by Etest in a central laboratory, considering Food and Drug Administration (FDA)/British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A total of 600 facultative/aerobic isolates (392 Gram negative, 208 Gram positive) and 100 anaerobes were tested. None of the 220 Escherichia coli isolates was resistant to tigecycline (MIC(50)/MIC(90) = 0.25/0.5 microg/mL), with 0.5% (FDA breakpoint) and 3.6% (BSAC/EUCAST breakpoint) intermediate strains. All Extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (15 strains), all Klebsiella pneumoniae, and Klebsiella oxytoca isolates (42 strains) were susceptible to tigecycline. No isolates resistant to tigecycline were found among Streptococcus viridans, Staphylococcus aureus, and Enterococcus faecium, but 18.9% of Enterococcus faecalis strains were intermediate following BSAC/EUCAST breakpoints. All (but 1) isolates of the Bacteroides fragilis group (n = 45) were tigecycline susceptible, as well as Gram-positive anaerobes. Tigecycline offers an adequate activity profile against isolates from secondary peritonitis when tested by Etest regardless of the breakpoints used for categorization.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Cohort Studies; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Peritonitis; Tigecycline

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Disk Diffusion Antimicrobial Tests; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tigecycline

We performed a retrospective and observational study of 51 patients treated with tigecycline, as the treatment for nosocomial infections due to multidrug-resistant microorganisms, to evaluate the superinfection rate and their etiologies. Superinfections were diagnosed in 12 (23.5%) patients (seven due to Pseudomonas aeruginosa, 13.7%) and one patient had P. aeruginosa colonization. Five patients with superinfection died (41.6%), three due to superinfections and two to underlying diseases. The superinfection rate observed during tigecycline treatment is higher than that previously reported. Pseudomonas aeruginosa is the most frequent agent, being the cause of 58.5% of all superinfections.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cross Infection; Female; Humans; Male; Middle Aged; Minocycline; Prevalence; Retrospective Studies; Superinfection; Tigecycline

Tigecycline is a new glycylcycline with broad-spectrum activity. Among these new agents, tigecycline is unique in generally having good activity against Gram-negative bacteria. Tigecycline has been approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Tigecycline had good activity against most ESBL-producing Enterobacteriaceae and may be a therapeutic alternative to carbapenems in some infections caused by ESBL-producing isolates, many of which are also multiresistant to quinolones, aminoglycosides, and classical tetracyclines.. One hundred and eight clinical isolates of Klebsiella spp. (64 K. pneumoniae and 44 K. oxytoca) were included. The susceptibility to selected antibiotics was tested by the disk-diffusion method. Tigecycline's MIC was determined by the Etest.. Of all the analyzed Klebsiella spp. strains, 31 (28.7%) produced ESBLs. Most of the Klebsiella spp. strains were susceptible to imipenem (100%), tigecycline (92.5%), and the combination of piperacilline and tazobactam (80.6%). Tigecycline exhibited high activity against Klebsiella strains, with MICs ranging from 0.19 to 4 microg/ml.. Tigecycline demonstrated excellent inhibitory activity against the analyzed strains. These data suggest that tigecycline, with an expanded broad-spectrum antimicrobial activity, may be an effective therapeutic option for the treatment of serious infections caused by Klebsiella strains.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Humans; Klebsiella; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is a novel antibiotic with activity against multidrug resistant bacteria. The aim of this study was to assess the efficacy of tigecycline use in serious hospital-acquired infections (HAI) CASE PRESENTATION: Prospective observational study of tigecycline use was conducted in a 1500 beds university hospital. From January 1, 2007 and January 31, 2010, 207 pts were treated with tigecycline for the following indications: intra-abdominal, pneumonia, bloodstream and complicated skin and soft tissue infections and febrile neutropenia. The therapy was targeted in 130/207 (63%) and empirical in 77/207 (37%) patients. All bacteria treated were susceptible to tigecycline. Median duration of tigecycline therapy was 13 days (range, 6-28). Clinical success was obtained in 151/207 (73%) cases, with the highest success rate recorded in intra-abdominal infections [81/99 (82%)]. Microbiological success was achieved in 100/129 (78%) treated patients. Adverse clinical events were seen in 16/207 patients (7.7%):. Considering the lack of data on tigecycline for critically ill patients, we think that the reported data of our clinical experience despite some limitations can be useful for clinicians.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cross Infection; Female; Hospitals, University; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Tigecycline; Time Factors; Treatment Outcome; Young Adult

A total of 5127 Acinetobacter spp. were collected from 140 hospitals in 32 countries in North America (17.1%), Europe (22.9%), Latin America (25.2%), and the Asia-Pacific (APAC) region (34.8%). Tigecycline MIC distributions were bimodal against isolates from North America and APAC region, while a unimodal pattern was noted for strains from Latin America. A variable MIC distribution was noted in Europe. Only tigecycline (MIC(50/90), 0.5/2 μg/mL) and polymyxin B (MIC(50/90), 0.5/1 μg/mL; 98.6% susceptible) exhibited high activity against Acinetobacter spp. Overall, tigecycline inhibited at least 90.0% of Acinetobacter spp. isolates from all countries evaluated at ≤2 μg/mL, as well as 95.0% of those displaying multidrug resistance. Other tested agents showed limited activity and a significant (P < 0.001) trend toward decreased susceptibility during the study period.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Asia; Cross Infection; Europe; Hospitals; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; North America; Polymyxin B; Tigecycline

Acinetobacter baumannii is a frequent cause of nosocomial infections in most hospitals. Management of infections caused by these strains is difficult, as the strains often display multiple drug resistance, including carbapenem. Tigecycline which is a glycylcycline derivative has antimicrobial activity against many gram-positive and gram-negative organisms. In this study, in vitro activity of tigecycline and carbapenems against clinical isolates of A.baumannii strains were investigated. A total of 100 A.baumannii isolates were collected from hospitalized patients with documented nosocomial infections [pneumonia (n = 39), surgical wound infection (n = 32), bacteremia (n = 16), catheter infection (n = 6), urinary tract infection (n = 5), peritonitis (n = 1), eye infection (n = 1)] between October 2006 and June 2007. Only one isolate per patient was included to the study. Minimum inhibitory concentrations (MIC) of tigecycline were determined by E-test (AB Biodisk, Sweden). Carbapenem resistance of A.baumannii strains were determined by disk diffusion method. All of the 100 A.baumannii isolates (100%) were found susceptible to tigecycline (MIC values ≤ 2 µg/ml; MIC ranges: 0.032-1.5 µg/ml). Imipenem susceptibility test was performed for 95 strains, and 36 (37.9%) were found sensitive, 18 (18.9%) were intermediate sensitive, and 41 (43.2%) were resistant. Meropenem susceptibility test was performed for 87 strains, and 22 (25.3%) were found sensitive, 9 (10.3%) were intermediate sensitive, and 56 (64.4%) were resistant. Since tigecycline is found quite effective on nosocomial A.baumannii isolates, it may be considered as a treatment alternative in infections caused by carbapenem-resistant Acinetobacter spp.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

This observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms.. Adult patients included, received TIG for >5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after >or=5 days of therapy despite in vitro susceptibility.. Forty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p<0.001).. TIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Analysis of Variance; Anti-Bacterial Agents; Bacteremia; Chi-Square Distribution; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Shock, Septic; Surgical Wound Infection; Tigecycline

To measure the in-vitro activity of various antibiotics including tigecycline against Gram negative and positive nosocomial aerobic isolates.. A total of 430 clinical isolates of both Gram positive (143) and negative (287) aerobic bacteria were used from 3 centres during the year 2006 and 2007. Minimum inhibitory concentration (MIC) was determined using broth micro dilution panels. Antibiotic resistance was interpreted using CLSI guidelines.. Most of the isolates were resistant to more than one drug. Resistance to tigecycline was not found. Tigecycline (1 microg/ml) had low MIC against organisms tested.. This data indicates that tigecycline, a new drug in its class, has broad-spectrum in-vitro activity against both Gram negative and positive nosocomial isolates. Therefore, it may be a suitable drug to be used for the treatment of highly resistant nosocomial infections.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Aerobic Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Pakistan; Tigecycline

The incidence of Acinetobacter baumannii infection has greatly increased over recent decades with infections occurring more in critically ill hospitalised patients. Hospital outbreaks of multiple antibiotic-resistant strains are posing an increasing threat to public health. Three different outbreaks of multidrug-resistant A. baumannii (MRAB) infections involving 24 patients, aged 16-75 years occurred in the intensive care unit in the course of one year. The isolates were cultured from clinical samples and identified using automated Vitek II ID system and the API 20NE system. Susceptibility testing was done by the E-test method. Molecular typing of the isolates was determined by pulsed-field electrophoresis. Screening of both patients and the environment was carried out. The acquisition time, i.e. the time of admission to time of acquiring infection, ranged from 3 to 31 days. All isolates were multiply resistant (MRAB), including resistance to carbapenems (MRAB-C) in the majority of cases but susceptible to tigecycline, with a minimum inhibitory concentration (MIC(90)) of 2 microg/mL. The overall mortality rate was 16.7%. Time-to-clearance of the MRAB-C was 8.3 days in the first outbreak, when tigecycline was not used, and 2.8 and 3.1 days during the second and third outbreaks, respectively, when tigecycline was used, and all but one patient survived. Environmental screening revealed gross contamination of many surfaces and equipment within the unit. The outbreak strains belonged to two distinct clones (D and E) whereas the 14 environmental strains belonged to three distinct groups (A-C). The outbreak of infections treated with tigecycline was successfully eliminated in conjunction with an aggressive infection control strategy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Typing Techniques; Carbapenems; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Environmental Microbiology; Humans; Incidence; Intensive Care Units; Microbial Sensitivity Tests; Middle Aged; Minocycline; Molecular Epidemiology; Tigecycline; Young Adult

A total of 569 nonduplicate isolates recovered from patients with community-onset or hospital-onset intraabdominal infections (IAIs) from 2001 to 2006 were studied. These included 28 Staphylococcus aureus and 541 Gram-negative isolates (33.6% Escherichia coli, 29.0% Klebsiella pneumoniae, 8.1% Acinetobacter baumannii, and 6.3% Pseudomonas aeruginosa). Minimum inhibitory concentrations (MICs) of the isolates to moxifloxacin, imipenem, and ciprofloxacin were determined using the agar dilution method and to tigecycline using the broth microdilution method. Extended-spectrum beta-lactamase (ESBL) producers were found in 15.5% (29 out of 182) of E. coli, 15.3% (24 out of 157) of K. pneumoniae, and 15.4% (2 out of 13) of K. oxytoca isolates. More than 85% of Enterobacteriaceae were susceptible to moxifloxacin, but this percentage was lower among E. coli (78%). The percentage of E. coli (K. pneumoniae) isolates that were not susceptible to moxifloxacin was 6% (0%) in 2001, 39% (17%) in 2003, and 21% (14%) in 2006. Tigecycline exhibited good in vitro activities against all S. aureus and >95% of all Enterobacteriaceae tested. Among the 24 isolates of ESBL-producing K. pneumoniae, 4 had tigecycline MICs > or = 2 microg/ml. Eighty percent of A. baumannii isolates exhibited tigecycline MICs of < or = 2 microg/ml. This study found that moxifloxacin and tigecycline exhibited good in vitro activity against bacterial isolates causing IAIs.

Topics: Anti-Bacterial Agents; Aza Compounds; Bacteria; Bacterial Infections; Bacterial Proteins; beta-Lactamases; Community-Acquired Infections; Cross Infection; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Peritonitis; Quinolines; Taiwan; Tigecycline

Nosocomial, intra-abdominal infections are extremely serious conditions, considering possibilities for their early diagnosis, as well as for their effective therapy. Multiresistant bacteria (Enterobacteriacae producing extended-spectrum beta-lactamases - ESBL Escherichia coli, Klebsiella species, vancomycin-resistant enterococci [VRE], and methicillin-resistant Staphylococcus aureus [MRSA]) are frequently isolated as pathogens of these infections. Tygecycline is among the novel wide- spectrum antibiotics affecting multiresistant bacteria, which are being introduced in clinical practice.. The aim of this study is to assess actual sensitivity of tygecycline to the commonest pathogens of intra-abdominal infections, generated in hospitalized surgical patients. Based on the sensitivity tests, tygecycline was indicated for targeted antibiotic therapy in intraabdominal infections.. Sensitivity to tygecycline, aminopenicillins, fluorochinoloni and gentamycine was established for the following bacteria: Escherichia coli, Klebsiella pneumonie, Enterobacter cloacea, Proteus mirabilis. Sensitivity to oxacillin, clincamycine and tygecycline was tested in Staphylococcus aureus, and to fluorochinolini, gentamycine and tygecycline in Enterococcus faecalis, and to fluorochinoloni, gentamycine, ceftazidime and gentamycine in Pseudomonas aeruginosa. Based on the sensitivity results, tygecycline was administered in two patients with postsurgical intra-abdominal infections caused by ESBL Escherichia coli and Klebsiella pneumonie. The initital dose of tygecycline was 100 mg i.v., followed by tygecycline 50 mg i.v. every 12 hours for 7 days.. The isolated bacteria showed 98-100% sensitivity to tygecycline, except Psudomonas aeruginosa, where 100% resistance was demonstrated. Targeted antimicrobial medication with tygecycline proved effective in postoperative nosocomial intra-abdominal infections, the both concerned patients recovered.. The choice of antimicrobial medication in nosocomial intra-abdominal infections requires through evaluation considering various factors including prior antibiotic therapy, co-morbidities and the current status of sensitivity with respect to potential multiresistant pathogens. Tygecycline shows significant in vitro efficacy against resistant gram-positive and key gram-negative facultative bacteria, which are a common cause of intra-abdominal infections in surgery patients. Clinical experience has shown that tygecycline is safe and effective in the treatment of complicated intra-abdominal infections.

Topics: Abdomen; Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Surgical Wound Infection; Tigecycline

Forty-two multidrug-resistant (MDR) Acinetobacter baumannii isolates were obtained during outbreaks in a Korean hospital. The co-carriage of bla(OXA-23), bla(OXA-51), bla(PER-1) and armA was observed in 23 isolates, and they were susceptible only to colistin and minocycline. The MDR A. baumannii isolates were found to belong to sequence group 1 using sequence-based typing.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Typing Techniques; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Korea; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Sequence Analysis, DNA

Topics: Asepsis; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Chlorhexidine; Cross Infection; Equipment Contamination; Humans; Minocycline; Rifampin; Silver Sulfadiazine

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Enteritis; Feces; Hematologic Diseases; Humans; Minocycline; Sputum; Tigecycline

Topics: Aged; Anti-Bacterial Agents; Carcinoma, Transitional Cell; Cross Infection; Drug Resistance, Multiple; Emphysema; Gram-Negative Bacterial Infections; Humans; Lupus Erythematosus, Discoid; Male; Minocycline; Obesity; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Stenotrophomonas maltophilia; Tigecycline; Urinary Bladder Neoplasms

In this study (part of the global TEST program), the in vitro activity of tigecycline, a member of a new class of antimicrobial agents, the glycylcyclines, against clinical isolates collected in Italy was evaluated.. A total of 200 clinical isolates were collected and identified in our institution during 2005. Minimum inhibitory concentrations (MICs) of the antimicrobial agents were determined by the broth microdilution method recommended by the CLSI in 2005.. Globally, 135 Gram-negative and 65 Gram-positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli, Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae with MIC(90)

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Italy; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of tigecycline and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The updated data obtained from the TEST program are integrated in a database server and available with a web application. The website has been designed to disseminate data collected from the international TEST program to the medical community and has been developed to be user-friendly. The use of this program-specific website can be made in a timely manner to extract antimicrobial resistance data of major microorganisms based on chosen selection criteria. This article describes how to use this web-based program for different analyse-types and the multiple options to display search results. Data can be presented in a table or as a graph or diagram, according to the source of the isolate, type of unit, resistance pattern of the pathogen. The website also allows the user to compare the data of antimicrobial testing at a national or regional level. It provides within a few minutes details on the activity of tigecycline and 11 comparators against clinical isolates collected all around the world. Main results of the TEST program on the in vitro activities of tigecyline against more 65,000 clinical isolates throughout the world are presented. The internet gives infectious diseases specialists and microbiologists the opportunity to have immediate access to continuously updated surveillance data. The TEST website should be helpful to clinicians to better select agents in severe infections, particularly for empirical treatment, that is at a time when the choice of the most appropriate antibiotic is essential for the outcome of the patient.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Data Display; Databases, Factual; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Global Health; Humans; Information Dissemination; Internet; Microbial Sensitivity Tests; Minocycline; Population Surveillance; Quality Control; Software; Species Specificity; Tigecycline

A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation determined the probability of target attainment (PTA) of tigecycline (+/- ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram-negative bacteria collected from worldwide surveillance and weighted by the expected prevalence of these pathogens causing HAP. For monotherapy, the weighted PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%), and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline, imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on contemporary resistance data, tigecycline plus ceftazidime is predicted to achieve its pharmacodynamic targets similarly to combination therapy with imipenem plus vancomycin for the treatment of patients with HAP.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Ofloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Tigecycline

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen that causes morbidity and mortality worldwide. The options for the treatment of MRSA infections are limited. Linezolid is an antibacterial agent of oxazolidinone group. It has a spectrum limited to gram-positive bacteria. Tigecycline is a broad-spectrum antibiotic of glycylcycline group. A total of 60 MRSA strains isolated from various clinical specimens were included in the study. Minimum inhibitory concentrations (MICs) were determined by Etest method, according to the Clinical and Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) criteria. The MIC(90) was 1 microg/ml for linezolid (range 0.094-4 microg/ml), and 0.38 microg/ml for tigecycline (range 0.032-1 microg/ml). All strains were found to be susceptible to linezolid, and only one strain's MIC value was above the threshold for tigecycline. Tigecycline and linezolid may represent therapeutic options for infections caused by MRSA.

Topics: Acetamides; Anti-Infective Agents; Cross Infection; Humans; Linezolid; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Tigecycline; Turkey

This study was performed to evaluate the in vitro activity of the amphibian peptide aurein 1.2 and to investigate its interaction with six antibiotics against nosocomial gram-positive cocci. All isolates were inhibited at concentrations of 1 to 16 mg/liter. Synergy was demonstrated when aurein 1.2 was combined with clarithromycin and minocycline.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cross Infection; Drug Synergism; Drug Therapy, Combination; Gram-Positive Cocci; Microbial Sensitivity Tests

Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Blotting, Southern; Carbapenems; China; Chloramphenicol; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Rifampin; Sequence Analysis, DNA

Topics: Acetamides; Anti-Bacterial Agents; Cross Infection; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecium; Glycopeptides; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Linezolid; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Tigecycline; Virginiamycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Strains of Klebsiella pneumoniae that produce one of three possible carbapenemases--KPC--have recently been identified with increasing frequency among isolates recovered from patients residing along the East Coast of the United States, particularly within the New York City metropolitan region. These strains have exhibited resistance to multiple antibiotic classes, including carbapenem agents. We report a case of nosocomial pneumonia and empyema caused by a KPC-producing isolate of K. pneumoniae at a large midwestern U.S. tertiary care facility in which the patient was treated with tigecycline. Although the pneumonia was treated successfully, the empyema recurred in association with a treatment-emergent tigecycline minimum inhibitory concentration (MIC) increase from 0.75 to 2 microg/ml. Clinicians should be aware of the potential occurrence of this treatment-emergent MIC increase, especially in the setting of sustained tigecycline therapy. In addition, the emergence of carbapenem-resistant Enterobacteriaceae reinforces the importance of antibiotic stewardship and strict infection control practices.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Drug Resistance, Multiple, Bacterial; Empyema; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1,947), North America (n = 24,283), Latin America (n = 1,957) and Europe (n = 8,796).. Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006. Only one isolate per patient was accepted. In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines.. Key organisms collected were Acinetobacter baumannii (n = 2,902), Enterobacter spp. (n = 5,731), Escherichia coli (n = 6,504), Klebsiella pneumoniae (n = 4,916), Pseudomonas aeruginosa (n = 5,128), Serratia marcescens (n = 2,313), Enterococcus faecalis (n = 2,701), Enterococcus faecium (n = 1,035) and Staphylococcus aureus (n = 5,753). Rates of methicillin resistance among S. aureus and of vancomycin resistance among enterococci were highest in North America (2,016/3,809, 52.9% and 571/2,544, 22.4%, respectively) and lowest in Europe (337/1,340, 25.1% and 36/916, 3.9%, respectively). Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC(90) values of 93% susceptibility in all regions) antimicrobials against the Gram-negative species, except for A. baumannii and P. aeruginosa. Piperacillin/tazobactam and amikacin were the most active against P. aeruginosa. Extended-spectrum beta-lactamase producers among K. pneumoniae occurred most frequently in Latin America (124/282, 44.0%).. Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections.

Topics: Anti-Bacterial Agents; Asia; Bacteria; Cross Infection; Drug Resistance, Bacterial; Europe; Global Health; Humans; Latin America; Minocycline; North America; Product Surveillance, Postmarketing; Tigecycline

Tigecycline is a new class of antibiotics active against emerging nosocomial pathogens as methicillin-resistant Staphylococcus aureus, extended spectrum (3-lactamases-producing enterobacteria and multidrug-resistant Acinetobacter sp. It was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections, but its pharmacological and microbiological profile is attractive to physicians for using it in other pathologies caused by resistant pathogens. The aim of this study was to evaluate in which indications tigecycline was used in Argentinian usual clinical settings during the first months after its launch. We analyzed tigecycline prescriptions in 69 patients with severe infections in 15 institutions. Fifteen patients (21%) received tigecycline for approved indications, and 54 (79%) for off label indications (56%) with scientific support and 23%> with limited or without any scientific support). The most frequent off label use was ventilator associated pneumonia (VAP) (36 patients). The etiology of the infections was established in 61%> of the patients. In all cases the isolated bacteria were multi-drug resistant (MDR) Acinetobacter s/?.-carbapenems included. Our study shows that the off label use of tigecycline is frequent, specially in VAP. One of the reasons could be that for MDR-Acinetobacter sp. -VAP, there are few therapeutic options (for instance: colistin). Physicians must evaluate the benefits/risks to use this antibiotic for indications that lack rigorous scientific support.

Topics: Anti-Bacterial Agents; Argentina; Cross Infection; Humans; Minocycline; Severity of Illness Index; Tigecycline; Treatment Outcome

Topics: Anti-Infective Agents, Local; Bacteremia; Carbon; Catheterization, Central Venous; Catheters, Indwelling; Cross Infection; Equipment Contamination; Humans; Minocycline; Platinum; Rifampin; Silver

The in vitro activities of tigecycline and selected antimicrobials were evaluated against a variety of multiple-drug-resistant clinical isolates, including extended-spectrum beta-lactamase- and/or metallo-beta-lactamase-producing gram-negative strains, colistin-resistant strains, vancomycin- and/or linezolid-resistant enterococci, and methicillin-resistant Staphylococcus aureus (MRSA). Tigecycline showed excellent activity against a collection of difficult-to-treat pathogens currently encountered in the hospital setting.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Greece; Humans; Minocycline; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the in vitro activity of tigecycline over a large population of organisms from geographically diverse sites. Tigecycline was compared to amikacin, ampicillin, amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and vancomycin against 3989 commonly encountered clinical Gram-negative and Gram-positive pathogens collected from sites in the United States during 2004. The tigecycline activity was equivalent to imipenem against Enterobacteriaceae. Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro results for tigecycline were similar to other broad-spectrum antimicrobial agents against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin susceptibility. Tigecycline MIC values were unaffected by penicillin nonsusceptibility and beta-lactamase production among fastidious respiratory pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity against most of the commonly encountered nosocomial and community-acquired bacterial pathogens.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, res

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Tigecycline

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Cross Infection; Denmark; Drug Resistance, Bacterial; Genes, Bacterial; Genotype; Humans; Minocycline; Streptococcal Infections; Streptococcus pyogenes; Tetracycline

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of Gram-positive and -negative bacterial pathogens. In vitro activity of tigecycline and comparator agents was determined for 3498 recent (2000-2003) strains of Staphylococcus aureus recovered from patients with either nosocomial or community-acquired infections. Oxacillin-susceptible and -resistant S. aureus from both patient populations displayed identical results for tigecycline (MIC(50) and MIC(90) results at 0.25 and 0.5 mg/L, respectively) and all strains were inhibited by 1 mg/L or less. While co-resistances to other antimicrobial classes were present in oxacillin-resistant strains, susceptibility to tigecycline remained unaffected, making the compound an attractive candidate for treatment of serious hospital as well as community-acquired staphylococcal infections.

Topics: Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Oxacillin; Staphylococcus aureus; Tigecycline

To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU.. Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999).. ICUs of a tertiary care hospital in Houston, TX.. Cancer patients in the medical ICU (MICU) and surgical ICU (SICU).. ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999.. The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999.. The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cause of Death; Child; Child, Preschool; Coated Materials, Biocompatible; Critical Care; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Enterococcus; Female; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Opportunistic Infections; Prospective Studies; Rifampin; Survival Rate; Texas; Vancomycin Resistance

To report the use of tetracyclines for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. Observational case series.. . The Presley Regional Trauma Center located within the Regional Medical Center, Memphis, Tennessee, USA.. Seven critically ill trauma patients with VAP caused by A. baumannii isolates that were resistant to all antibiotics tested except for doxycycline or minocycline.. Patients were treated with IV doxycycline or minocycline for an average of 13.5 (range 9-20) days.. Doxycycline or minocycline was successful in six of seven patients.. Doxycycline or minocycline may be effective for treating multidrug-resistant A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Cross Infection; Doxycycline; Drug Resistance, Multiple, Bacterial; Humans; Infection Control; Infusions, Intravenous; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Tennessee; Trauma Centers; Treatment Outcome

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow Transplantation; Catheterization, Central Venous; Catheters, Indwelling; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance; Female; Humans; Infection Control; Leukemia; Male; Middle Aged; Minocycline; Neutropenia; Rifampin; Staphylococcal Infections; Texas

Topics: Bacteria; Community-Acquired Infections; Critical Pathways; Cross Infection; Drug Costs; Drug Resistance, Microbial; Humans; Infusions, Intravenous; Minocycline; Pneumonia, Bacterial

In the early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in our geriatric wards, including 190 beds, MRSA infection was prevalent. In the early 1980's in our geriatric wards minocycline was one of the most sensitive antibiotics to MRSA isolated in our wards and used frequently against MRSA pneumonias and bacteremia. In the late 1980's resistant strains of MRSA to minocycline rapidly increased because vancomycin was not allowed to introduced for treatment of MRSA before 1991 in Japan. At the same period the predominant coagulase type changed from type II to type VII. To decrease minocycline-resistant strains to MRSA after 1987, use of minocycline was limited. Moreover since Oct. 1991 to decrease nosocomial infections some active preventive measures against hospital infection, including limited use of 2nd and 3rd cephems, were taken. In this study changing patterns of coagulase type of Staphylococcus aureus were discussed. At least 4 years was needed to find out that the predominant coagulase type changed from type VII to type II again in 1991. In this study about 22 antimicrobial agents MICs of 313 strains of Staphylococcus aureus isolated between March 1992 and June 1993 were determined and compared with the data of MICs before introduction of preventive measures. The pattern of susceptibility to MINO was in part improved. Thus the some sensitive strains of S. aureus were observed again in our geriatric wards. Interestingly indeed it took approximately 5 years to find out the emergence of sensitive strains to MINO since limitation of use of MINO in 1987.

Topics: Bacterial Typing Techniques; Coagulase; Cross Infection; Drug Resistance, Microbial; Geriatrics; Hospital Units; Humans; Minocycline; Staphylococcus aureus

A big problem of nosocomial infections is some refractory infections, so that present important nosocomial infections are deep infections by MRSA and weakly virulent gram-negative bacilli such as Pseudomonas aeruginosa, which are not susceptible to many antimicrobial agents. It is also noteworthy that MRSA can infect to both immunonormal and immunocompromised patients, although clinical signs of that infection are much more severe in the latters. On the other hand, weakly virulent bacilli can infect to only immunocompromised patients. Immunocompromised states are divided into two categories, namely general and local deficiencies. The mechanism of general immunodeficiency is mainly depend upon leukopenia or diminishment of phagocytic activity of them, and that of local immunodeficiency is bases on formation of biofilms which protect bacteria from phagocytosis and killing effect of antimicrobial agents. In this paper, it is emphasized that both countermeasure for nosocomial infections and adequate use of antimicrobial agents or immunomodulators are necessary to decrease number of patients with hospital infections.

Topics: Cross Infection; Disinfection; Granulocyte Colony-Stimulating Factor; Humans; Methicillin Resistance; Minocycline; Premedication; Pseudomonas Infections; Staphylococcal Infections; Vancomycin

In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Cross Infection; Drug Therapy, Combination; Humans; Infection Control; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Mupirocin; Plasmids; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Cefotiam; Cross Infection; Drug Therapy, Combination; Glycopeptides; Humans; Imipenem; Methicillin Resistance; Minocycline; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

Using an agar dilution assay, for 66 of 104 (63.5%) clinical isolates of Acinetobacter calcoaceticus biovar anitratus, the MIC of ciprofloxacin was greater than or equal to 1.0 micrograms/ml. Cross resistance was demonstrable to ciprofloxacin and gentamicin (P less than 0.001), amikacin (P less than 0.01), cefotaxime (P less than 0.001), azlocillin (P less than 0.001), ceftazidime (P less than 0.001), trimethoprim-sulfamethoxazole (P less than 0.001), and minocycline (P less than 0.05). The mean MIC of ciprofloxacin for drug-susceptible isolates was consistently lower than that for resistant isolates; however, these differences were significant only for amikacin (P = 0.036).

Topics: Acinetobacter; Anti-Bacterial Agents; Ceftazidime; Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Microbial Sensitivity Tests; Minocycline

Topics: Aged; Alcaligenes; Aortic Valve Insufficiency; Cross Infection; Drug Therapy, Combination; Humans; Hypertension; Male; Minocycline; Sepsis; Vancomycin

Pseudomonas cepacia, considered a phytopathogenic organism for many years, has been shown recently to be widely distributed geographically. The hospital environment has become an important source of this organism but the resistance of Ps. cepacia to most antibiotics has made the treatment of infections a problem. One hundred per cent of the strains tested have proved to be sensitive to the sulphonamides and to novobiocin, 93.0% to the combination of trimethoprim and sulfamethoxazole (co-trimoxazole); 85.2% to minocycline; 77.8% to chloramphenicol and dibekacin and 44.4% to nalidixic acid. One hundred per cent of the strains exhibit resistance to ampicillin, cephalothin, cefamandole, cefoxitin, colistin, cefuroxime, tetracycline and cefazolin; 88.9% to amikacin, tobramycin and sisomycin; 85.2% to carbenicillin. The new beta-lactams, apalcillin, ceftazidime, N-formimidoyl-thienamycin, piperacillin, cefotaxime and azlocillin proved to be the most potent of the molecules tested, inhibiting 90% of the strains, at concentrations of 4, 8, 8, 8, 32 and 16 mg/l and 100% of the strains at 8, 16, 16, 32, 32 and 64 mg/l, respectively. In contrast to the usual sensitivity patterns of Pseudomonas spp, Ps. cepacia has been shown to be resistant to colistin, cefsulodin and the aminoglycosides. However, unlike Ps. aeruginosa, Ps. cepacia has been shown, by the dilution method, to be sensitive to co-trimoxazole, 92.3% of the strains being inhibited by 16 mg/l.

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Combinations; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Novobiocin; Pseudomonas; Pseudomonas Infections; Species Specificity; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Carrier State; Cross Infection; Demeclocycline; Doxycycline; Drug Resistance, Microbial; Humans; Lincomycin; Microbial Sensitivity Tests; Minocycline; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tetracycline