minocycline and Bacterial-Infections

The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Drug Therapy, Combination; Hospitals; Humans; Minocycline; Pneumonia; Prognosis; Tigecycline

Anaerobes are the most predominant components of the normal human skin and mucous membranes bacterial flora, and are a frequent cause of endogenous bacterial infections. Anaerobic infections can occur in all body locations: the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. Treatment of anaerobic infection is complicated by their slow growth in culture, by their polymicrobial nature and by their growing resistance to antimicrobials. Antimicrobial therapy is frequently the only form of therapy needed, whereas in others it is an important adjunct to drainage and surgery. Because anaerobes generally are isolated mixed with aerobes, the antimicrobial chosen should provide for adequate coverage of both. The most effective antimicrobials against anaerobes are: metronidazole, the carbapenems (imipenem, meropenem, doripenem, ertapenem), chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitors (ampicillin or ticarcillin plus clavulanate, amoxicillin plus sulbactam, piperacillin plus tazobactam), tigecycline, cefoxitin and clindamycin.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamase Inhibitors; Carbapenems; Cefoxitin; Chloramphenicol; Clindamycin; Drug Resistance, Bacterial; Humans; Metronidazole; Minocycline; Penicillins; Tigecycline

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; History, 21st Century; Humans; Minocycline; Tigecycline

Tigecycline, the first member of the glycylcyclines, has been approved for complicated skin and soft tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs). It has a wide range of activity against Gram-positive and Gram-negative bacteria, including anaerobes. Since its approval, the worldwide clinical use of tigecycline has been heterogeneous, either as a monotherapy or as a part of combination therapy, almost exclusively at the standard dosage, in patients with community-acquired (CA) infections as well as health-care associated (HCA) or nosocomial infections (HA), including infections caused by multidrug-resistant (MDR) bacteria. In recent years, issues and warnings of an increased mortality in these heterogeneous patients treated with tigecycline have been raised by meta-analyses and by regulatory agencies. Re-defining tigecycline therapy is a proposal, based on epidemiological, clinical, microbiological and pharmacological considerations, to distinguish patients who may be treated with monotherapy, according to the official indications and dosages, from those treated with combination treatment, mostly with high dosages in the setting of nosocomial IAIs, possibly caused by MDR bacteria or as a carbapenem-sparing strategy. Whilst available clinical data and guidelines suggest caution with monotherapy in severe infections, experience worldwide indicates that combination treatment with high-dosage tigecycline is increasingly used.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Minocycline; Tigecycline

Tigecycline is approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) in adults. In this analysis the safety and tolerability profile of tigecycline (used alone or in combination) for the treatment of patients with approved indications of cSSTI and cIAI were examined under real-life clinical conditions.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). A total of 254 cSSTI and 785 cIAI patients were included. The mean age was 63 years; 34.4% and 56.6% were in intensive care units, 90.9% and 88.1% had at least one comorbidity and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the beginning of treatment were 15.0 ± 7.9 and 16.9 ± 7.6, respectively.. Data on adverse events (AEs) were available for 198 cSSTI and 590 cIAI patients in three studies. Nausea and vomiting were reported in ≤ 2% of patients. The most common serious AEs were multi-organ failure (4.0% and 10.0% in cSSTI and cIAI patients, respectively) and sepsis (4.0% and 6.1%, respectively). Death was recorded for 24/254 (9.4%) cSSTI and 147/785 (18.7%) cIAI patients. Mortality rates were higher in the group with a baseline APACHE II score of >15 compared with those with a score of ≤ 15 (18.7% versus 3.5% for cSSTI patients and 23.8% versus 16.0% for cIAI patients). A similar trend was seen when cIAI patients were stratified by Sequential Organ Failure Assessment (SOFA) score.. The safety and tolerability of tigecycline, alone and in combination, are consistent with the level of critical illness among patients in these real-life studies.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Antimicrobial drug resistance is a growing problem in Europe and, even with differences in epidemiology, it is of great concern. The treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) is hindered further by pathogens that are resistant to methicillin, carbapenems, third-generation cephalosporins and glycopeptides.. An analysis of the microbiological results from five European observational studies (July 2006 to October 2011) evaluating the efficacy of tigecycline (prescribed as monotherapy or in combination with other antibacterials) for the treatment of cSSTI and cIAI is presented.. In total, 213 cSSTI and 623 cIAI patients were included; 34.4% and 56.6%, respectively, were critically ill in intensive care units. At baseline, at least one pathogen was isolated in 167 (78.4%) cSSTI and 464 (74.5%) cIAI patients, and 32.9% and 49.1% of infections were polymicrobial. In cSSTI, Staphylococcus aureus and Escherichia coli (52.7% and 18.0%, respectively) were the most frequently isolated pathogens, whereas in cIAI most infections were due to E. coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%). Clinical response was observed in >80% of patients with E. coli in both cIAI and cSSTI. In cSSTI patients, the clinical response rate to S. aureus was 80.8%. For cIAI, 77.4% of E. faecium and 79.5% of E. faecalis patients responded to treatment.. Tigecycline when given alone or in combination with other antibacterials appeared to be efficacious against multiple pathogens, affirming its role in real-life clinical practice as a broad-spectrum antibacterial for the treatment of patients with cSSTI and cIAI, including the critically ill, across Europe.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

There is limited information on the use of tigecycline in real-life clinical practice. This analysis aims to identify and understand tigecycline prescribing patterns and associated patient outcomes for approved indications.. A pooled analysis of patient-level data collected on the prescription of tigecycline in five European observational studies (July 2006 to October 2011) was conducted.. A total of 1782 patients who received tigecycline were included in the analysis. Of these patients, 61.6% were male, the mean age was 63.4 ± 14.7 years, 56.4% were in intensive care units, 80.2% received previous antibiotic treatment and 91% had one or more comorbid conditions. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 17.7 ± 7.9 and 7.0 ± 4.0, respectively. The majority of patients (58.3%) received tigecycline for treatment of complicated skin and soft-tissue infections (cSSTIs; n = 254) or complicated intra-abdominal infections (cIAIs; n = 785). Tigecycline was given at the standard dose (100 mg plus 50 mg twice daily) to 89.3% of patients for a mean duration of 11.1 ± 6.4 days. The main reasons for prescribing tigecycline were failure of previous therapy (46.1%), broad-spectrum antibiotic coverage (41.4%) and suspicion of a resistant pathogen (39.3%). Tigecycline was prescribed first-line in 36.3% of patients and as monotherapy in 50.4%. Clinical response rates to treatment with tigecycline alone or in combination were 79.6% (183/230; cSSTIs) and 77.4% (567/733; cIAIs).. Although tigecycline prescription behaviour showed some heterogeneity across the study sites, these results confirm a role for tigecycline in real-life clinical practice for the treatment of complicated infections, including those in critically ill patients, across Europe.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Prescriptions; Europe; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

Tigecycline (TIG) exhibits broad-spectrum activity against many Gram-positive and Gram-negative pathogens. However, clinical resistance has emerged recently and has been detected following treatment with TIG. This observation suggests that long-term monotherapy may carry a high risk for TIG resistance. TIG resistance is observed most frequently in Acinetobacter baumannii and Enterobacteriaceae, especially in multidrug-resistant strains. Resistance-nodulation-cell division (RND)-type transporters and other efflux pumps may be factors for decreased sensitivity to TIG. Therefore, TIG should be cautiously used in the clinic, and efflux-mediated resistance should be closely monitored in order to prolong the lifespan of this useful antibiotic.

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

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Meta-Analysis as Topic; Minocycline; Survival Analysis; Tigecycline; Treatment Outcome

Tigecycline is a novel glycylcycline that exhibits broad-spectrum antibacterial activity. Recently, the US FDA issued a warning concerning increased mortality with tigecycline in randomized controlled trials (RCTs).. We conducted a systematic review and meta-analysis of RCTs that compared tigecycline with any other antibiotic regimen for the treatment of any infection. A comprehensive search, without publication status or other restrictions, was conducted. The primary outcome was overall 30 day mortality. The secondary outcome included clinical and microbiological failure, superinfections and adverse events (AEs). The trials' risks of bias and their effects on results were assessed. Two reviewers independently extracted the data. Individual trials' relative risks (RRs) were pooled using a fixed effect meta-analysis.. Fifteen trials (7654 patients) were included. Overall mortality was higher with tigecycline compared with other regimens [RR 1.29, 95% confidence interval (CI) 1.02-1.64, without heterogeneity]. The type of infection assessed and the trials' reported risks of bias did not affect this result. Clinical failure was significantly higher with tigecycline (RR 1.16, 95% CI 1.06-1.27) and non-statistically significant higher rates of microbiological failure were demonstrated (RR 1.13, 95% CI 0.99-1.30). Development of septic shock was significantly more frequent with tigecycline (RR 7.01, 95% CI 1.27-38.66). Superinfections were significantly more common with tigecycline and so were AEs, including all AEs and AEs requiring discontinuation.. In the light of the increased mortality, probably explained by decreased clinical and microbiological efficacy, clinicians should avoid tigecycline monotherapy in the treatment of severe infections and reserve it as a last-resort drug.

Topics: Anti-Bacterial Agents; Bacterial Infections; Confidence Intervals; Humans; Minocycline; Randomized Controlled Trials as Topic; Shock, Septic; Tigecycline; Treatment Failure; Treatment Outcome

Multidrug resistance among bacteria increases the need for new antimicrobial drugs with high potency and stability. Tigecycline is one candidate drug, and a previous meta-analysis of only published randomised controlled trials suggested that it might as effective as comparator treatments; we did a meta-analysis to include new and unpublished trials to assess its efficacy for the treatment of adult patients with serious bacterial infection.. We searched PubMed, Cochrane Central Register, and Embase up to March 30, 2011, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. Eligible studies were randomised trials assessing the clinical efficacy, safety, and eradication efficiency of tigecycline versus other antimicrobial agents for any bacterial infection. The primary outcome was treatment success in patients who received at least one dose of the study drug, had clinical evidence of disease, and had complete follow-up (the clinically assessable population). Meta-analysis was done with random-effects models because of heterogeneity across the trials.. 14 randomised trials, comprising about 7400 patients, were included. Treatment success was lower with tigecycline than with control antibiotic agents, but the difference was not significant (odds ratio 0·87, 95% CI 0·74-1·02). Adverse events were more frequent in the tigecycline group than in the control groups (1·45, 1·11-1·88), with significantly more vomiting and nausea. All-cause mortality was higher in the tigecycline group than in the comparator groups, but the difference was not significant (1·28, 0·97-1·69). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small.. Tigecycline is not better than standard antimicrobial agents for the treatment of serious infections. Our findings show that assessment with unpublished studies is needed to make appropriate decisions about new agents.. None.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Male; Middle Aged; Minocycline; Randomized Controlled Trials as Topic; Tigecycline

Tigecycline is a novel antibacterial agent with a wide spectrum of antimicrobial activity that includes pathogens with clinically significant resistance patterns. The clinical effectiveness of tigecycline has been evaluated in several non-inferiority, phase III, randomized, double-blind, controlled clinical trials regarding, mainly, complicated skin and skin structure infections and complicated intra-abdominal infections. Clinical data regarding the effectiveness of tigecycline against infections caused by multidrug-resistant pathogens that commonly affect severely ill patients as well as community acquired pneumonia are favorable, yet limited. The consideration of the pharmacokinetic and pharmacodynamic properties of tigecycline may aid in further understanding the therapeutic role of this agent. Respectively, the utility of tigecycline in the treatment of severe infections involving the bloodstream has not been substantiated, particularly regarding pathogens with borderline susceptibility. Moreover, the fact that a relatively small proportion of the administered tigecycline dose is excreted unchanged in the urine may compromise the effectiveness of this agent in serious urinary tract infections. Increasing the dose of tigecycline to maximize effectiveness against severe infections appears as an appealing therapeutic option, considering the linear pharmacokinetics exhibited by this agent. However, gastrointestinal toxicity (nausea and vomiting) is usually dose-limiting. Further research is recommended on therapeutic strategies to optimize the effectiveness and safety of tigecycline therapy in severely ill patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Randomized Controlled Trials as Topic; Tigecycline

Increasing antimicrobial resistance and infection complications pose challenges to optimal antibiotic therapy. Paucity of new antibiotics (and the eventual bacterial resistance they face) highlights the critical need for more appropriate use of broadly effective agents, which may help to thwart the dramatic rise in global resistance. Single agents that can be combined effectively with others, if needed, promise the simplest overall utility. Approved in 2005 to treat complicated skin and intra-abdominal infections, tigecycline is a novel extended-spectrum minocycline derivative that circumvents bacterial resistance, as it is unaffected by efflux pumps and ribosomal protection. However, tigecycline should not be used as empiric monotherapy for treatment of health-care associated infections known or suspected to be owing to Pseudomonas aeruginosa or Proteus spp.. This article summarizes the demonstrated clinical utility of tigecycline so far.. A MEDLINE search examined authoritative published clinical studies, reviews and case reports detailing the clinical record of tigecycline since 2004.. Tigecycline continues to maintain satisfactory profiles of safety, efficacy and antimicrobial resistance avoidance. Regardless, continued surveillance is needed to detect reduced susceptibility and resistance against both community and nosocomial pathogens. Judicious use of agents reserved for multidrug resistant pathogens is vital to preserve their effectiveness.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cost-Benefit Analysis; Drug Interactions; Drug Resistance, Bacterial; Humans; Minocycline; Tigecycline

The cumulative ecological damage, both to the individual patient and to patient populations, secondary to antibiotic prescribing is increasingly recognised. The impact of antibiotics on pathogens and normal flora should be a criterion for antimicrobial selection. Measures to reduce the use of third-generation cephalosporins and fluoroquinolones should be considered. Increased reliance on carbapenems may accelerate the emergence of extremely resistant isolates, and these antimicrobials should be restricted to key scenarios. There is a clear need for new agents with novel modes of action and low ecological damage potential to treat nosocomial infections. Tigecycline has a spectrum of activity that theoretically may reduce the selection pressure for key nosocomial pathogens, and represents an alternative to carbapenems. Further studies are needed to confirm this potentially low selection pressure.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Prescriptions; Drug Resistance, Bacterial; Drug Utilization; Humans; Minocycline; Selection, Genetic; Tigecycline

The advanced macrolides, azithromycin and clarithromycin, and the ketolide, telithromycin, are structural analogs of erythromycin. They have several distinct advantages when compared with erythromycin, including enhanced spectrum of activity, more favorable pharmacokinetics and pharmacodynamics, once-daily administration, and improved tolerability. Clarithromycin and azithromycin are used extensively for the treatment of respiratory tract infections, sexually transmitted diseases, and Helicobacter pylori-associated peptic ulcer disease. Telithromycin is approved for the treatment of community-acquired pneumonia. Severe hepatotoxicity has been reported with the use of telithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Humans; Ketolides; Macrolides; Minocycline; Tetracyclines; Tigecycline

This brief review summarizes recently published data on the pharmacokinetics and pharmacodynamics of tigecycline in man. Significant pharmacokinetic data are now available from the studies of infected patients, as is information on tissue distribution. Importantly, drug exposure-response relationships have been established for complicated skin and skin structure infections and intra-abdominal infection. These studies highlight the difficulties of undertaking pharmacodynamic studies in humans where account must be taken of both mixed pathogen infections and the potential impact of surgery. These data help to define the clinical role for tigecycline.

Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Female; Humans; Male; Minocycline; Peritonitis; Skin Diseases, Bacterial; Tigecycline; Tissue Distribution

Tigecycline (pronounced tie-ge-sigh-cleen; Tygacil--Wyeth) is a broad-spectrum antibacterial and the first glycylcycline to be marketed in the UK. It is active against certain resistant bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and bacteria that produce extended-spectrum beta-lactamase (ESBL). Tigecycline is licensed for intravenous treatment of adults with complicated skin and soft tissue infections, and complicated intra-abdominal infections. We review tigecycline and assess its place for these infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Costs; Humans; Minocycline; Tigecycline

Infections caused by multidrug-resistant gram-negative bacteria are an increasing problem worldwide. Treatment of these microorganisms is a challenge because resistance limits dramatically therapeutic options. In this review, we discuss data of in vitro susceptibility and clinical studies of possible agents for the management of these infections. Currently, published data are limited, and there are no randomized clinical trials involving the treatment of infections caused by multidrug-resistant gram-negative rods. For imipenem-resistant Acinetobacter spp., most studied options are polymyxins and sulbactam. No newer antimicrobials active against Pseudomonas aeruginosa are available or under investigation. Tigecycline presents a broad spectrum of activity in vitro but has been studied mainly as treatment of community-acquired infections, as has ertapenem. They are potential options against extended-spectrum beta-lactamase-producing Enterobacteriaceae, and tigecycline may be useful in treating Acinetobacter infections.

Topics: Acinetobacter; Bacterial Infections; beta-Lactamases; beta-Lactams; Clinical Trials as Topic; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Ertapenem; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Pseudomonas aeruginosa; Sulbactam; Tigecycline

Multidrug microbial resistance poses major challenges to the management of infection, particularly with the paucity of new drugs with activity against these bacteria. Since the turn of this century a few new antibiotics have been licensed, including linezolid, daptomycin and tigecycline. This supplement reports data presented at the 13th International Congress of Infectious Diseases held in Kuala Lumpur in June 2008. Dr R. Isturiz reviews the data on global resistance trends and the potential impact on empirical therapy; Dr J.-H. Song reviews new agents on the antimicrobial horizon; and the final paper in the supplement, by Dr L.R. Peterson, reviews the role of tigecycline in the management of complicated intra-abdominal and skin and soft tissue infections.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Daptomycin; Drug Resistance, Microbial; Humans; Linezolid; Minocycline; Oxazolidinones; Tigecycline

The dawn of a troubling post-antibiotic era likely is on the horizon, fuelled by a rise in bacterial resistance to existing antibiotic therapy alongside a waning pipeline of novel antibacterial agents. Tigecycline, a new glycylcycline with an expanded broad spectrum of in vitro activity, was recently approved for the treatment of complicated skin and soft tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs). This review will examine how tigecycline evades the common mechanisms of antibiotic resistance, the metabolism and pharmacokinetics of tigecycline, and its spectrum of in vitro activity. The results of randomized clinical trials for the treatment of cSSTIs and cIAIs with tigecycline are also described, as is the patient safety and tolerability observed during these studies. Tigecycline monotherapy has been shown to be as effective as its comparators and, against a backdrop of rising bacterial resistance, the role for tigecycline in monotherapy of infections from Gram-positive, Gram-negative and anaerobic bacteria is a meaningful development.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Minocycline; Tigecycline

To review the literature on tigecycline, a novel antibiotic.. References were identified through MEDLINE (1966-February 2007) and International Pharmaceutical Abstracts (1970-February 2007) databases, using the key words tigecycline, glycylcycline, complicated skin and skin structure infections (cSSSI), complicated intraabdominal infections (cIAI), and in vitro. Additional articles for this review were identified by reviewing the bibliographies of articles cited. The package insert was also used as a reference.. In vitro, clinical, and pharmacokinetic studies evaluating tigecycline's safety and efficacy were selected.. A tigecycline 100 mg intravenous loading dose followed by an intravenous infusion of 50 mg every 12 hours was shown in clinical trials to be as effective as comparator antibiotics in treating cSSSI and cIAI. Tigecycline has a broad spectrum of activity that includes many resistant bacteria with few treatment options, such as methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing bacteria such as Escherichia coli and Klebsiella pneumoniae. In cSSSI studies, tigecycline was found to be noninferior to vancomycin plus aztreonam with test-of-cure rates of 86.5% and 88.6%, respectively. Tigecycline was also found to be noninferior to imipenem/cilastatin in cIAI studies; clinical cure rates were 86.1% and 86.2%, respectively. In vitro activity has been demonstrated against other multidrug-resistant microorganisms of concern, such as Acinetobacter spp. Although it has a broad spectrum of activity, tigecycline has inadequate activity against Pseudomonas spp. Nausea and vomiting were the most frequently reported adverse effects.. Tigecycline is approved for the treatment of cSSSI and cIAI infections. To date, little resistance to tigecycline has been reported; however, with widespread use of the drug, resistance will likely occur. Since published studies have not dealt with seriously ill patients, it is recommended that, until further studies have been completed, other agents be used in the treatment of these patients unless no option other than tigecycline exists.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Minocycline; Tigecycline

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Double-Blind Method; Drug Resistance, Bacterial; Glycylglycine; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Antiporters; Bacterial Infections; Bacterial Proteins; Doxycycline; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Minocycline; Protein Synthesis Inhibitors; Tetracycline; Tetracycline Resistance; Tetracyclines; Tigecycline

There is a clinical need for new treatment options as a result of continued increase in the expression of resistance among bacterial pathogens. A number of compounds currently in development show promise. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore, daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. It has rapid bactericidal activity against growing and stationary-phase bacteria, once-daily dosing regimen, and has a low potential for the development of resistance. It has been approved for the treatment of complicated skin and soft tissue infections caused by Gram-positive bacteria, and registration for treatment of infective endocarditis and bacteraemia is anticipated. Daptomycin is a welcome addition to the antimicrobial armamentarium for the treatment of bacterial infections. Tigecycline is a new glycyclcycline antimicrobial recently approved for use in the USA, Europe and elsewhere. While related to the tetracyclines, tigecycline overcomes many of the mechanisms responsible for resistance to this class. It is a novel broad spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. This review aims to summarise the key clinical data of daptomycin and tigecycline which hold promise for widespread clinical use in the next decade.

Topics: Anti-Infective Agents; Bacterial Infections; Cardiovascular Infections; Daptomycin; Humans; Minocycline; Tigecycline

Anaerobic bacteria are the predominant flora in the normal human skin and mucous membranes and are, therefore, a common cause of endogenous infections. Since anaerobic infections are generally polymicrobial, where anaerobes are mixed with aerobic organisms, therapy should provide coverage of both types of pathogens. The isolation of anaerobes requires appropriate methods of collection, transportation and cultivation of specimens. The lack of use of any of these methods can lead to inadequate recovery of anaerobes and inappropriate therapy. Treatment of anaerobic infection is complicated by the slow growth of these organisms and the growing resistance of anaerobic bacteria to antimicrobials. The primary role of antimicrobials is to limit the local and systemic spread of infection. Surgical drainage is of primary importance. This includes debriding of necrotic tissue, draining the pus, improving circulation, alleviating obstruction and increasing tissue oxygenation. The most effective antimicrobials against anaerobic organisms are metronidazole, the carbapenems (imipenem, meropenem and ertapenem), chloramphenicol, the combinations of a penicillin and a beta-lactamase inhibitor (ampicillin or ticarcillin plus clavulanate, amoxicillin plus sulbactam, and piperacillin plus tazobactam), tigecycline and clindamycin.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Chloramphenicol; Clindamycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Metronidazole; Microbial Sensitivity Tests; Minocycline; Negative-Pressure Wound Therapy; Penicillins; Tigecycline

Topics: Adult; Aged; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Female; Humans; Infusions, Intravenous; Middle Aged; Minocycline; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Skin Diseases, Infectious; Tigecycline; Treatment Outcome; United States; United States Food and Drug Administration

Lack of progress in developing new antimicrobials, particularly new classes, as opposed to variants of existing agents, has contributed to the emergence of antibiotic-resistant pathogens.. Data synthesis after review of pertinent English-language literature.. The development of new classes of antimicrobial agents is crucial, considering the increasing prevalence of nosocomial pathogens resistant to empiric as well as second- and third-line antibiotic choices. Tigecycline has recently been approved for the treatment of complicated skin and skin structure as well as intra-abdominal infections. Published data on the in vitro and in vivo properties of tigecycline, the first-in-class glycylcycline, are reviewed.. It is plausible that tigecycline could to some extent replace available broadspectrum agents for approved indications and thereby reduce the selective pressure for some currently prevalent multi-resistant pathogens in the hospital setting.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Approval; Drug Resistance, Bacterial; Humans; Minocycline; Practice Patterns, Physicians'; Tigecycline

The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, adverse events, dosage and administration, drug interactions, and place in therapy of tigecycline are reviewed.. Tigecycline is the first of a new class of antimicrobials, the glycylcyclines, to receive approved labeling from the Food and Drug Administration. Similar to tetracyclines, glycylcyclines contain the central four-ring carbocyclic skeleton, with a substitution at the D-9 position. This substitution confers expanded broad-spectrum activity and defense against antimicrobial efflux pumps and ribosomal protection mechanisms. Tigecycline covers a broad spectrum of gram-positive (including resistant isolates), gram-negative (including extended-spectrum beta-lactamase producing organisms), and anaerobic pathogens. It does not exhibit activity against Pseudomonas aeruginosa and Proteus species. Clinical efficacy has been demonstrated in complicated skin and skin structure infections and intraabdominal infections. Tigecycline is administered intravenously and exhibits linear pharmacokinetics. The drug does not undergo extensive metabolism and works independently of the cytochrome P-450 isoenzyme system and therefore does not affect medications metabolized by these enzymes. Tigecycline is administered as a 100-mg i.v. loading dose followed by 50 mg i.v. every 12 hours. Hepatic dosage adjustment is necessary for severe disease; however, no dosage adjustments are necessary for patients with renal impairment.. Tigecycline is an alternative agent available for the treatment of resistant gram-negative and gram-positive infections, especially in patients with a history of a penicillin allergy or antimicrobial-related toxicities.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Multiple, Bacterial; Humans; Kidney Diseases; Liver Diseases; Minocycline; Tigecycline

Tigecycline (GAR-936) is the first glycylcycline antibiotic to be approved by the US Food and Drug Administration (FDA). The drug overcomes the 2 major resistance mechansisms of tetracycline: drug-specific efflux pump acquisition and ribosomal protection. Tigecycline is active against many gram-positive and -negative organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and -resistant enterococci, and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. It is also active against many anaerobic bacteria, as well as atypical pathogens, including rapidly growing, nontuberculous mycobacteria. Tigecycline is concentrated in cells and is eliminated primarily via biliary excretion. Diminished renal function does not significantly alter its systemic clearance. Furthermore, tigecycline does not interfere with common cytochrome P450 enzymes, making pharmacokinetic drug interactions uncommon. It provides parenteral therapy for complicated skin/skin-structure and intra-abdominal infections. The only prominent adverse effects are associated with tolerability, most notably nausea and vomiting. Tigecycline will be most useful as empirical therapy for polymicrobial infections, especially in cases in which deep tissue penetration is needed or in which multidrug-resistant pathogens are suspected.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram-positive, gram-negative, and anaerobic activity, including certain multidrug-resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug-resistant gram-positive pathogens including methicillin-resistant and glycopeptide-intermediate and -resistant Staphylococcus aureus, as well as vancomycin-resistant enterococci. Multidrug-resistant gram-negative pathogens, such as Acinetobacter baumannii and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad-spectrum antimicrobials are available to combat multidrug-resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however, further clinical experience will clarify its role as a broad-spectrum agent.

Topics: Animals; Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Drug Administration Schedule; Drug Interactions; Drug Resistance, Multiple, Bacterial; Endocarditis, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Osteomyelitis; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Tigecycline

The advent of vancomycin-resistant enterococci in the 1990s and the threat posed by vancomycin resistance in Staphylococcus aureus led to the development of several new antimicrobial agents active against these pathogens. Quinupristin/dalfopristin was the first such drug to be commercially available but adverse effects have meant that the drug is now rarely used. Linezolid, the first antimicrobial of the oxazolidinone class, has met with more widespread use and has both an intravenous and an oral formulation. Daptomycin is a lipopeptide antimicrobial that is rapidly bactericidal against S. aureus. It is effective in the therapy of S. aureus bloodstream infections but is inactivated by pulmonary surfactant, making it of no use in the therapy of pneumonia. Tigecycline, by contrast, is bacteriostatic against most pathogens but has a broad spectrum of antimicrobial activity and has enhanced penetration into many tissues. Other new antibiotics (dalbavancin, telavancin, ceftobiprole and doripenem) are currently under clinical development and hold promise for widespread clinical use in the next decade.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Infections; Daptomycin; Humans; Linezolid; Minocycline; Oxazolidinones; Staphylococcal Infections; Streptococcal Infections; Tigecycline; Virginiamycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The increasing antimicrobial resistance found in the many clinically important species of bacteria that commonly cause serious and life-threatening diseases presents a difficult challenge for clinicians, especially when an appropriate initial therapy must be chosen. New antibiotics are urgently needed to address the formidable issues associated with infections caused by vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and multidrug-resistant Gram-negative bacteria. The need for new antibiotics that effectively resist antimicrobial mechanisms of resistance has become paramount. 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 the use of tigecycline for many serious and life-threatening infections for which the use of other antibiotics is no longer appropriate. Tigecycline is a novel expanded spectrum antibiotic that appears poised to meet the latest bacterial challenges facing clinicians, including the serious and life-threatening infections caused by highly resistant bacteria. Tigecycline, moreover, appears to hold promise as a new, versatile antibiotic that can be chosen for empirical therapy, even as a single agent, for initial therapy of many clinically important infections.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is a new semisynthetic glycylcycline for the treatment of serious infections. Of the glycylcyclines, tigecycline is the most studied and appears to hold promise as a new antimicrobial agent that can be administered as monotherapy to patients with many types of serious bacterial infections. For patients with serious infections, the initial choice for empirical therapy with broad-spectrum antibiotics is crucial, and, if the choice is inappropriate, it may have adverse consequences for the patient. Tigecycline has been designed to overcome many existing mechanisms of resistance among bacteria and confers broad antibiotic coverage against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and many species of multidrug-resistant gram-negative bacteria. Tigecycline has been efficacious and well tolerated in human clinical phase 2 studies, which warranted further evaluation of tigecycline in larger studies for treatment of many indications, including complicated skin and skin-structure infections, complicated intra-abdominal infections, and infections of the lower respiratory tract.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Structure; Tigecycline

Tigecycline is the first glycylcycline to be launched and is one of the very few new antimicrobials with activity against Gram-negative bacteria. It evades acquired efflux and target-mediated resistance to classical tetracyclines, but not chromosomal efflux in Proteeae and Pseudomonas. Cmax+ is low, but tissue penetration is excellent and the compound has shown equivalence to imipenem/cilastatin in intra-abdominal infection and to vancomycin plus aztreonam in skin and skin structure infection. Tigecycline may prove particularly useful for treatment of surgical wound infections, where both gut organisms and MRSA are likely pathogens. It is also likely to find a role in the treatment of infections due to multiresistant pathogens, including Acinetobacter spp. and ESBL producers, as well as MRSA and enterococci.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Minocycline; Molecular Structure; Tigecycline

Tigecycline derived from minocycline. It is part of a new class of antibiotics called glycylcyclines. Tigecycline is given intravenously and has activity against a variety of gram-positive and gram-negative bacterial pathogens, many of which are resistant to existing antibiotics. Tigecycline successfully completed phase III trials in which it was at least equal to intravenous vancomycin and aztreonam to treat complicated skin and skin structure infections (cSSSI), and to intravenous imipenem and cilastatin to treat complicated intra-abdominal infections (cIAI). Tigecycline side effects are primarily digestive upset. It should be a valuable addition to the armamentarium to treat even the most resistant pathogens.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Tigecycline

Treatment of complicated skin and skin structure infection (cSSSI) and complicated intra-abdominal infection (cIAI) currently present a therapeutic challenge because many of the pathogens involved are becoming resistant to standard antimicrobial therapy. Tigecycline is a novel glycylcycline that exhibits expanded broad-spectrum antibacterial activity against certain resistant pathogens. Results from randomised Phase III studies comparing the clinical and microbiological efficacy of tigecycline with combination antimicrobial therapy for the treatment of cSSSI and cIAI are encouraging. Tigecycline has the potential to be used as monotherapy for the treatment of cSSSI and cIAI.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Humans; Intestinal Diseases; Minocycline; Skin Diseases, Bacterial; Tigecycline

Tigecycline is the first member of a new class of broad-spectrum antibacterials, the glycylcyclines, that has been specifically developed to overcome the two major mechanisms of tetracycline resistance (ribosomal protection and efflux). In vitro, tigecycline was active against a wide range of Gram-positive and -negative aerobic and anaerobic bacteria implicated in complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs). Intravenously administered tigecycline (recommended dosage regimen 100 mg initially, followed by 50 mg every 12 hours for 5-14 days) has been approved by the US FDA for the treatment of cSSSIs and cIAIs. In well designed, pivotal phase III studies, tigecycline monotherapy was noninferior to combination therapy with vancomycin 1 g plus aztreonam 2 g every 12 hours in hospitalised adult patients with cSSSIs (two trials; pooled clinical cure rates, 86.5% vs 88.6%) or broad-spectrum therapy with imipenem/cilastatin 200-500 mg/200-500 mg every 6 hours in hospitalised adult patients with cIAIs (two trials; pooled clinical cure rates, 86.1% vs 86.2%). Tigecycline was generally well tolerated in phase III studies; nausea, vomiting and diarrhoea were the most frequent adverse events in patients treated with tigecycline or an active comparator (vancomycin plus aztreonam or imipenem/cilastatin).

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Minocycline; Tigecycline

Despite the development of extended-spectrum penicillins, cephalosporins, and quinolones, the older antimicrobial agents, doxycycline, minocycline, TMP-SMX, clindamycin, and metronidazole, still play an important role in the treatment of infectious diseases. All of these older drugs are well absorbed by the oral route, attaining serum levels equivalent to those achieved by parenteral administration. The availability of generic forms of the older drugs reduces their cost. Besides traditional uses, some older drugs have become the preferred therapy for newly recognized infectious diseases. Doxycycline is the preferred drug for rickettsial tickborne diseases, ehrlichiosis and early Lyme disease. TMP-SMX is the preferred drug for I. belli and Cyclospora. Minocycline has been used to treat MRSA and MRSE infections. Clindamycin or metronidazole combined with a quinolone is an excellent oral regimen for polymicrobial infections. [table: see text]

Topics: Anti-Bacterial Agents; Bacterial Infections; Chloramphenicol; Clindamycin; Clinical Trials as Topic; Doxycycline; Drug Resistance, Multiple; Humans; Metronidazole; Microbial Sensitivity Tests; Minocycline; Prognosis

Since it is a disease mainly caused by plaque--an aggregate of various bacteria--periodontal disease can be considered a local infection. Thus, it has seemed reasonable to utilize antibiotics to suppress the intrapocket bacteria, specifically or nonspecifically. When antibiotics are administered orally, however, massive doses over a prolonged period of time are needed to attain a therapeutic effect. This increases the risk of adverse reactions as well as developing resistant strains of bacteria. To overcome these problems, local drug delivery systems (LDDS) were devised to combat the local infection. However, the intrapocket antibiotic delivery systems have yet to be fully evaluated for clinical effectiveness; to prove the therapeutic effectiveness of locally administered antibiotics, the drug must reach the base of the periodontal pocket and the effective concentration of the antibiotic against the pathogenic bacteria must be maintained for a long time. This concise review presents with figures, tables, and a comprehensive list of references the many studies which have used the various tetracyclines as LDDS to treat periodontal disease.

Topics: Administration, Topical; Anti-Bacterial Agents; Bacterial Infections; Biodegradation, Environmental; Delayed-Action Preparations; Drug Delivery Systems; Humans; Minocycline; Periodontal Pocket; Tetracycline; Therapeutic Irrigation

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

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

Topics: Animals; Bacterial Infections; Humans; Minocycline; Tetracycline Resistance; Tetracyclines

Topics: Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Tetracycline Resistance; Tetracyclines

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Bacterial Infections; Bacteroides Infections; Cephalosporins; Drug Hypersensitivity; Haemophilus Infections; Humans; Meningococcal Infections; Minocycline; Penicillin Resistance; Penicillins; Streptococcal Infections; Typhoid Fever

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

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

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

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

This randomized clinical study compared the antibacterial effectiveness of treatment protocols using either a triple antibiotic solution (1 mg/mL) or calcium hydroxide/chlorhexidine paste as interappointment medication in infected canals of teeth with primary apical periodontitis.. The root canals of single-rooted teeth with apical periodontitis were prepared by using a reciprocating single-instrument technique with 2.5% sodium hypochlorite irrigation and then medicated for 1 week with either a triple antibiotic solution (minocycline, metronidazole, and ciprofloxacin) at 1 mg/mL (n = 24) or a calcium hydroxide paste in 2% chlorhexidine gluconate (n = 23). Samples were taken from the canal at the baseline (S1), after chemomechanical preparation (S2), and after intracanal medication (S3). DNA extracts from clinical samples were evaluated for total bacterial reduction using a 16S ribosomal RNA gene-based quantitative polymerase chain reaction assay.. All S1 samples were positive for the presence of bacteria, and counts were substantially reduced after treatment procedures (P < .01). Bacterial levels in S2 and S3 samples did not significantly differ between groups (P > .05). S2 to S3 reduction was 97% in the antibiotic group and 39% in the calcium hydroxide/chlorhexidine group; only the former reached statistical significance (P < .01). There were significantly more quantitative polymerase chain reaction-negative S3 samples in the antibiotic group than in the calcium hydroxide group (P < .05).. Interappointment medication with a triple antibiotic solution at the concentration of 1 mg/mL significantly improved root canal disinfection, and its effects were at least comparable with the calcium hydroxide/chlorhexidine paste. Effectiveness and easy delivery of the antibiotic solution make it an appropriate medicament as part of a disinfecting protocol for conventional nonsurgical endodontic treatment and possibly regenerative endodontic procedures.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Calcium Hydroxide; Chlorhexidine; Ciprofloxacin; Dental Disinfectants; Female; Humans; Male; Metronidazole; Middle Aged; Minocycline; Ointments; Periapical Periodontitis; Root Canal Irrigants; Root Canal Preparation; Solutions; Young Adult

Tigecycline, a broad-spectrum antibiotic used for treating serious bacterial infections in adults, may be suitable for pediatric use once an appropriate dosage is determined.. The aim of this study was to assess the pharmacokinetic (PK) properties, safety profile, and descriptive efficacy of tigecycline.. In this Phase II, multicenter, open-label clinical trial, children aged 8 to 11 years with community-acquired pneumonia (CAP), complicated intra-abdominal infection (cIAI), or complicated skin and skin structure infections (cSSSI) were administered tigecycline 0.75, 1, or 1.25 mg/kg.. A total of 58 patients received ≥ 1 dose of tigecycline (31 boys; 44 white; mean age, 10 years; mean weight, 35 kg); 47 had data from samples available for PK analysis. The mean (SD) PK values were: C(max), 1899 (2954) ng/mL; T(max), 0.56 (0.18) hour; between-dose AUC, 2833 (1557) ng · h/mL; weight-normalized clearance, 0.503 (0.293) L/h/kg; and Vd(ss), 4.88 (4.84) L/kg. Overall clinical cure rates at test-of-cure were 94% (16/17), 76% (16/21), and 75% (15/20) in the 0.75-, 1-, and 1.25-mg/kg cohorts, respectively. The rates of protocol violations were higher in the 1- and 1.25-mg/kg groups, resulting in higher proportions of indeterminate clinical cure assessments relative to the 0.75-mg/kg cohort (19% and 15% vs 0%). The most frequent adverse event was nausea, which occurred in 50% of patients overall (29/58) and the prevalence of which was significantly higher in the 1.25-mg/kg group versus the 0.75-mg/kg group (65% vs 18%; P = 0.007). Pharmacodynamic simulations using MIC data from an ongoing microbiological surveillance trial predicted that a dosage of 1.2 mg/kg q12h would lead to therapeutic target attainment levels of up to 82% for the target AUC(0-24)/MIC ratios.. A tigecycline dosage of ∼1.2 mg/kg q12h may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections. ClinicalTrials.gov identifier: NCT00488345.

Topics: Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Child; Female; Humans; Male; Minocycline; Tigecycline

Patients with intra-abdominal infections differ with regard to the type of infection and the severity of illness. However, the impact of these factors, together with differences in drug exposure, on clinical response is not well understood. Using phase 2 and 3 data for patients with complicated intra-abdominal infections, the relative importance of tigecycline exposure, host factors, and disease factors, alone or in combination, for the probability of clinical response was examined. Patients with complicated intra-abdominal infections who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for 5 to 14 days and who had adequate clinical, pharmacokinetic, and response data were evaluated. Multivariable logistic regression was used to identify factors associated with clinical response. A final multivariable logistic regression model demonstrated six factors based on 123 patients to be predictive of clinical success: a weight of <94 kg (P = 0.026), the absence of Pseudomonas aeruginosa in baseline cultures (P = 0.021), an APACHE II score of <13 (P = 0.029), non-Hispanic race (P = 0.005), complicated appendicitis or cholecystitis (P = 0.004), and a ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) of > or =3.1 (P = 0.003). The average model-predicted probability of clinical success when one unfavorable factor was present was 0.940. This probability was lower (0.855) when the AUC/MIC ratio was < 3.1 and the remaining five factors were set to the favorable condition. The average model-predicted probability of clinical success in the presence of two unfavorable factors was 0.594. These findings demonstrated the impact of individual and multiple factors on clinical response in the context of drug exposure.

Topics: Abdominal Cavity; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria, Anaerobic; Bacterial Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Predictive Value of Tests; Tigecycline; Treatment Outcome; Young Adult

The in vitro activity of tigecycline and comparative antimicrobial agents was evaluated against 1828 primary baseline pathogens isolated from 844 patients enrolled in the phase 3 clinical trials investigating the efficacy of tigecycline in diabetic foot infection (DFI). The trials were global, enrolling patients in 30 countries. Tigecycline was active against the most prevalent pathogens in DFI, including Gram-positive and Gram-negative isolates of both aerobic and anaerobic bacteria with 95% of MICs < or =2 microg/mL for the entire collection. The spectrum of activity of tigecycline included important pathogens for DFI, such as Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis. As reported previously, Pseudomonas aeruginosa and several pathogens in the Proteeae group were generally less susceptible to tigecycline by comparison to other Gram-negative pathogens. The excellent in vitro expanded broad-spectrum activity of tigecycline in the clinical isolates confirmed the potential utility of tigecycline for pathogens associated with DFIs.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Diabetic Foot; Double-Blind Method; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; Wound Infection

To report our experience of tigecycline use in a medical and surgical intensive care unit. To describe its prescription, microbiology findings, tolerance and efficacy.. Prospective, observational, single center study.. All consecutive patients treated with tigecycline were included. Demography, indication of treatment, bacteriology before, during and in the month after treatment and ICU mortality were collected. The main endpoints were clinical and microbiological efficacy and tolerance.. Twenty-four patients were included. In half of the cases, tigecycline was prescribed in monotherapy for a complicated intra-abdominal infection. Overall tolerance of tigecycline was good. Clinical and microbiological cure was obtained in six cases, not obtained in nine, indeterminate in six cases and not evaluable in the three cases of prophylaxis. During the treatment, four bacteria commonly sensitives were shown to be resistant to tigecycline.. Our pilot study on 24 patients suggests that tigecycline is well tolerated in critically ill patients. Clinical cure in severe infections was compromised in nine patients essentially because of resistant pathogens suggesting its prescription on antibiogram. However, the impact of association or the increasing doses in severe critically ill patients should be evaluated.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Care; Humans; Middle Aged; Minocycline; Pilot Projects; Prospective Studies; Severity of Illness Index; Tigecycline

Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.. In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for /=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005).. Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.. ClinicalTrials.gov NCT00136201.

Topics: Adult; Aged; Anti-Bacterial Agents; Asian People; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Male; Middle Aged; Minocycline; Peritonitis; Tigecycline; Treatment Outcome

Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores > or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtained in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI.

Topics: Abdomen; Anti-Infective Agents; Bacteria; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Male; Metronidazole; Middle Aged; Minocycline; 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, a first-in-class expanded glycylcycline antimicrobial agent, has demonstrated efficacy in the treatment of complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal (cIAI) infections. A population pharmacokinetic (PK) model for tigecycline was developed for patients with cSSSI or cIAI enrolled in two phase 2 clinical trials, and the influence of selected demographic factors and clinical laboratory measures was investigated. Tigecycline was administered as an intravenous loading dose followed by a 0.5- or 1-h infusion every 12 h for up to 14 days. Blood samples were collected the day before or the day of hospital discharge for the determination of serum tigecycline concentrations. Patient covariates were evaluated using stepwise forward (alpha = 0.05) and backward (alpha = 0.001) procedures. The predictive performance of the model was assessed separately using pooled data from either two phase 3 studies for patients with cSSSI or two phase 3 studies for patients with cIAI. A two-compartment model with zero-order input and first-order elimination adequately described the steady-state tigecycline concentration-time data. Tigecycline clearance was shown to increase with increasing weight, increasing creatinine clearance, and male gender (P < 0.001). The final model provided a relatively unbiased fit to each data set. Individual predicted values of the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) were generally unbiased (median prediction error, -1.60% to -3.78%) and were similarly precise (median absolute prediction error, <4%) when compared across data sets. The population PK model provided the basis to obtain individual estimates of steady-state AUC(0-12) in later exposure-response analyses of tigecycline safety and efficacy in patients with cSSSI or cIAI.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Female; Humans; Male; Middle Aged; Minocycline; Models, Statistical; Population; Skin Diseases, Infectious; Tigecycline

This pooled analysis includes 2 phase 3, double-blind trials designed to evaluate the safety and efficacy of tigecycline, versus that of imipenem-cilastatin, in 1642 adults with complicated intra-abdominal infections. Patients were randomized to receive either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 h) or imipenem-cilastatin (500/500 mg intravenously every 6 h) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-42 days after therapy) in the co-primary end point microbiologically evaluable and microbiological modified intent-to-treat populations. For the microbiologically evaluable group, clinical cure rates were 86.1% (441/512) for tigecycline, versus 86.2% (442/513) for imipenem-cilastatin (95% confidence interval for the difference, -4.5% to 4.4%; P < .0001 for noninferiority). Clinical cure rates in the microbiological modified intent-to-treat population were 80.2% (506/631) for tigecycline, versus 81.5% (514/631) for imipenem-cilastatin (95% confidence interval for the difference, -5.8% to 3.2%; P < .0001 for noninferiority). Nausea (24.4% tigecycline, 19.0% imipenem-cilastatin [P = .01]), vomiting (19.2% tigecycline, 14.3% imipenem-cilastatin [P = .008]), and diarrhea (13.8% tigecycline, 13.2% imipenem-cilastatin [P = .719]) were the most frequently reported adverse events. This pooled analysis demonstrates that tigecycline was efficacious and well tolerated in the treatment of patients with complicated intra-abdominal infections.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Intestinal Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.. A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.. A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.. This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Topics: Abdomen; Adult; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Cholecystitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Diverticulitis; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Minocycline; Peptic Ulcer Perforation; Peritonitis; Tigecycline

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

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

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

A group of 41 patients, all admitted to hospital because of acute purulent exacerbations of chronic respiratory disease, were treated with either doxycycline or minocycline in a double-blind randomized study. Drug dosage was one 100 mg capsule twice daily for seven days. Bacteriological and clinical assessment before and immediately after treatment showed no significant differences between the doxycycline and the minocycline groups, nor did further evaluation after seven days follow-up. Pharmacokinetic studies showed that the Cmax and 0-11 h AUC values in blood were higher for doxycycline, whereas the sputum Cmax was, on average, higher for minocycline because of the greater penetration of the latter. The MIC values for the two antibiotics differed slightly, usually, but not always, in favour of minocycline. Problems were experienced with both agents in the eradication of Haemophilus influenzae. The net clinical results with the two drugs were identical.

Topics: Adult; Bacterial Infections; Bronchitis; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Doxycycline; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Minocycline; Moraxella catarrhalis; Pneumococcal Infections; Random Allocation; Streptococcus pneumoniae; Tetracyclines

The efficacy and safety of minocycline were compared with that of amoxicillin in the treatment of 58 patients with acute bacterial sinusitis. The most frequently isolated pathogens were streptococci, staphylococci, and Haemophilus influenzae. After therapy for a mean time of 11 days, clinical cure or improvement and bacterial eradication were evident in 100% of the patients treated with minocycline and in 95% of the patients treated with amoxicillin. Roentgenographic results indicated clearing or improvement in 91% of the minocycline recipients and in 70% of those who received amoxicillin. These differences between treatments were not statistically significant. A low incidence of generally mild adverse clinical experiences occurred in both treatment groups. Thus, minocycline and amoxicillin were equally safe and effective in the treatment of these patients with acute bacterial sinusitis.

Topics: Adolescent; Adult; Aged; Amoxicillin; Bacterial Infections; Child; Female; Gastrointestinal Diseases; Haemophilus influenzae; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Radiography; Random Allocation; Sinusitis; Skin Diseases; Staphylococcus aureus; Streptococcus; Tetracyclines

The relative safety and efficacy of minocycline and cephalexin were examined in patients with acute or chronic prostatitis. The multicenter study was of single-blind, parallel-group design. Forty-two men received minocycline (200-mg initial dose followed by 100 mg twice daily) and 44, cephalexin (500 mg four times daily); each antibiotic was administered orally for four weeks. A follow-up period of patient assessment extended for an additional six weeks. Evaluable data were available for 20 minocycline-treated patients and for 24 cephalexin-treated patients. Clinical cure or improvement without recurrence was seen in 65 per cent of the patients who received minocycline and in 46 per cent of those given cephalexin. Bacteriologic cure without relapse or reinfection occurred in 45 per cent of the minocycline-treated men and in 21 per cent of the cephalexin-treated men. Serious adverse clinical experiences were not encountered in either treatment group. Although several factors, mainly the small number of patients, precluded a statistical analysis of comparative efficacy, it was evident that more patients in the minocycline-treated group had both clinical and bacteriologic cures (35%) than did those in the cephalexin-treated group (21%).

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Cephalexin; Clinical Trials as Topic; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prostatitis; Random Allocation; Research Design; Tetracyclines; Time Factors

Seventy patients admitted for abdominal surgery requiring short-term perioperative prophylaxis were randomized to receive minocycline + gentamicin or metronidazole + gentamicin. Thirty patients were considered to be infected at the time of surgery and were treated with the same regimen. In the prophylactic cohort, one patient from each group developed postoperative fever. One patient receiving minocycline developed a wound infection. The overall infection rate was 2.6%. In the treatment cohort, it appeared that the patients receiving metronidazole had more severe underlying diseases than those receiving minocycline. Consequently, more postoperative non-infectious complications were observed in the former. Minocycline + gentamicin appeared at least as effective than metronidazole + gentamicin in preventing postoperative infectious complications associated with abdominal surgery or in treating intra-abdominal infections.

Topics: Abdomen; Adult; Aged; Bacterial Infections; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Metronidazole; Middle Aged; Minocycline; Postoperative Complications; Premedication; Random Allocation; Tetracyclines

Topics: Adult; Appendicitis; Bacterial Infections; Child; Clinical Trials as Topic; Female; Humans; Intestinal Perforation; Male; Middle Aged; Minocycline; Penicillins; Peritonitis; Postoperative Care; Streptomycin; Tetracyclines

Topics: Adult; Aged; Ampicillin; Bacterial Infections; Bronchial Diseases; Clinical Trials as Topic; Doxycycline; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Minocycline; Tetracyclines

Topics: Administration, Oral; Bacterial Infections; Clinical Trials as Topic; Female; Humans; Injections, Intravenous; Male; Minocycline; Respiratory Tract Infections; Skin Diseases, Infectious; Tetracycline; Urinary Tract Infections

Topics: Adenoviridae; Adenoviridae Infections; Bacterial Infections; Clinical Trials as Topic; Humans; Influenza, Human; Lung; Minocycline; Neisseria meningitidis; Orthomyxoviridae; Paramyxoviridae Infections; Pneumonia; Pneumonia, Viral; Respiratory System; Respirovirus; Sputum; Tetracycline; Trachea

Tigecycline with broad-spectrum activity against pathogens has advantages in the treatment of severe infections in clinical. Accompany with the huge increase of tigecycline usage, more side effects began to arouse people's attention. The aim of this study was to assess the impact of tigecycline treatment on peripheral blood platelet in patients with severe infections. We retrospectively retrieved demographic and laboratory data in 24 cases of tigecycline-treated patients with severe infections. 18 patients (75%) who were administered tigecycline experienced a decrease in platelet count. The ages of platelet decrease group are significant older than normal group. In the platelet decreased group, the platelet count was significant decreased after 3 days tigecycline treatment. 9 patients' platelet count recovered in 5 days after tigecycline treatment withdraw. Platelet decrease in patient after tigecycline treatment, which can be reversed after tigecycline discontinuation. Tigecycline-induced platelet decrease is associated with age.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood Platelets; Humans; Minocycline; Retrospective Studies; Tigecycline

The knowledge about pathogens and their antibiotic susceptibility patterns is essential to select an appropriate antibiotic.. We investigated the microbiological profile in pancreatic and extrapancreatic infections, and antibiotic sensitivity pattern in patients with acute pancreatitis.. Of 556 patients with acute pancreatitis, only 189 developed bacterial infection; however, bacteremia was present in 42 patients (7.6%). Culture-proven infected pancreatic necrotic collection was present in 161 patients (29%). Escherichia coli and Klebsiella pneumoniae were the most common organisms. Among the bacterial infection cohort, 164 patients developed multidrug-resistant bacterial infection. Infection with multidrug-resistant bacteria, especially at multiple sites, increased mortality. Nearly 50% of patients (n = 94) acquired extremely drug-resistant bacterial infection at some time and emerged as key reason for prolonged hospital and intensive care unit stay. Colistin resistance and tigecycline resistance were documented in 2.1% and 17.2% of the specimens at admission and in 4.6% and 21% of specimens during the hospital stay. Of 556 patients, 102 patients developed fungal infection and 28 patients had only fungal infection without bacterial infection.. Colistin and tigecycline are best reserved as last-resort antibiotics. Fungal infection was found to be associated with increased mortality, median hospital stay, and intensive care unit stay.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Microbial; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Mycoses; Outcome Assessment, Health Care; Pancreatitis; Tigecycline

Because patients with abdominal solid organ transplants (SOTs) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad-spectrum therapies for polymicrobial IAIs in this population.. Retrospective cohort study.. Large academic medical center with multiple outpatient clinics.. A total of 81 adult SOT recipients were included who were treated for confirmed or suspected polymicrobial IAIs from 2007-2012. Of these patients, 27 received tigecycline and 54 received comparator therapy with a broad-spectrum β-lactam (e.g., piperacillin-tazobactam, cefepime, or meropenem) with or without glycopeptide or lipopeptide gram-positive therapy (vancomycin or daptomycin) (comparator group). Patients in the comparator group were matched to tigecycline-treated patients based on transplant type (kidney, combined kidney-pancreas, combined kidney-liver, or solitary pancreas) in a 1:2 ratio (tigecycline-to-other broad-spectrum antibiotics).. Data on patient demographics, comorbidities, and clinical variables were collected and compared by using bivariate analyses. Clinical outcomes-clinical cure, improvement or failure, and disease recurrence-as well as death within 1 year were analyzed by bivariate analyses and logistic regression. Clinical cure was lower in the tigecycline group versus the comparator group (40.7% vs 72.2%, p=0.008), but cure combined with improvement was similar between the two groups (85.2% vs 88.9%, p=0.724). Multiple logistic regression analysis showed that treatment with comparator antibiotics increased the odds of cure (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.15-12.27) and reduced the odds of treatment failure (OR 0.59, 95% CI 0.07-4.55) and death within 1 year (OR 0.79, 95% CI 0.22-2.86); however, patients receiving comparator antibiotics were more likely to have disease recurrence (OR 1.45, 95% CI 0.33-6.36). Patients receiving tigecycline experienced a higher rate of adverse events than those receiving comparator antibiotics (29.6% vs 9.3%, p=0.026).. Patients receiving tigecycline were less likely to achieve optimal clinical outcomes and had more adverse events. Alternative regimens should be selected over tigecycline for the treatment of polymicrobial IAIs in abdominal SOT recipients until additional studies are completed to examine its role in this population.

Topics: Academic Medical Centers; Adult; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Female; Humans; Intraabdominal Infections; Logistic Models; Male; Middle Aged; Minocycline; Organ Transplantation; Recurrence; Retrospective Studies; Tigecycline; Transplant Recipients

Background The broad spectrum antibiotic tigecyline has promising efficacy against many multidrug-resistant (MDR) pathogens. However, when used clinically, many reports about treatment failures of tigecycline monotherapy indicate that it might not be sufficient to control severe infections. Combination therapy has become an option to treat infection with MDR bacteria because of the distinct advantage in terms of broad coverage, synergistic effect and prevention of drug resistance development. Methods Search terms 'tigecycline', 'GAR-936' and 'glycylcycline' combined with the term 'combination' were applied to retrieve the available in vitro and in vivo studies on tigecycline combination therapy from PubMed database (January 1993-August 2015). Results Colistin-tigecycline was the most studied combination and showed promising efficacy. Other combination regimens, such as tigecycline plus sulbactam, carbapenem or rifampicin, also showed synergistic effects against different bacteria. However, most of the data was from in vitro and animal studies. Only some case reports indicated that tigecycline containing combination therapy had favourable outcomes. Conclusions Although this study could not conclude that combination therapy with tigecycline was superior to monotherapy, when severe infection leaves no other choice, selection of combination drugs according to infection status and in vitro susceptibility testing is recommended. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapy compared to tigecyline monotherapy.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Mice; Minocycline; Tigecycline

Bacterial organisms (n = 13,494) were consecutively collected in 2011-2014 from 21 Latin American medical centres (11 nations). Antimicrobial susceptibility was determined by broth microdilution at a central laboratory. Tigecycline was very active against Gram-positive organisms, with MIC50/90 values of 0.06/0.06 µg/mL for Staphylococcus aureus (n = 2878), 0.06/0.12 µg/mL for coagulase-negative staphylococci (n = 880), 0.06/0.06 µg/mL for enterococci (n = 708) and ≤0.03/≤0.03-0.06 µg/mL for streptococci (n = 1352). All Gram-positive species exhibited 100.0% susceptibility (FDA and/or EUCAST criteria), except for Streptococcus pneumoniae (99.8% susceptible). The S. aureus oxacillin resistance rate varied from 28.0% (Brazil) to 55.0% (Argentina), and the overall vancomycin resistance rate was 15.5% (Enterococcus faecium, 50.3%; and Enterococcus faecalis, 2.3%). The E. faecium vancomycin resistance rate varied from a low (26.3%) in Argentina to a high (71.7%) in Brazil. Against Enterobacteriaceae (n = 4543), tigecycline MIC50/90 values were 0.25/1 µg/mL; 98.3% and 94.2% of strains were considered susceptible according to FDA and EUCAST breakpoints, respectively. Overall, 37.7% and 57.3% of Escherichia coli and Klebsiella pneumoniae exhibited the CLSI ESBL screening phenotype. The highest CLSI ESBL screening phenotype rates among E. coli and Klebsiella spp. strains were observed for isolates collected from Mexico (69.9%) and Chile (69.9%), respectively. Occurrence of carbapenem-resistant Enterobacteriaceae was substantially higher in Brazil (9.0%) and Argentina (6.3%) compared with Chile and Mexico (0.4-0.7%). Tigecycline was also active against Acinetobacter spp. (MIC50/90, 1/2 µg/mL; 92.3/72.1% inhibited at ≤2/≤1 µg/mL) and Stenotrophomonas maltophilia (MIC50/90, 0.5/2 µg/mL; 91.5/83.0% inhibited at ≤2/≤1 µg/mL).

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Epidemiological Monitoring; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; Tigecycline

In the context of globally increasing antimicrobial resistance, tigecycline appears to be a useful therapeutic option. The need for prolonged courses for complex infections has prompted consideration of its use via outpatient parenteral antibiotic therapy (OPAT) programmes, although clinical outcomes when used in this setting remain unknown. We retrospectively reviewed the patient characteristics and outcomes of 11 patients who received tigecycline, most commonly delivered as 100 mg once daily, via OPAT at three tertiary Australian hospitals. Rates of co-morbidity and prior antibiotic use were high. Patients had a wide range of infections including bone and/or joint (n = 5), intra-abdominal (n = 3), lower respiratory tract (n = 2) and parapharyngeal abscess (n = 1). Mycobacterial species (n = 5) were the most frequent pathogen, and multi-resistant organisms were common (n = 4). The median OPAT duration was 14 days (IQR 6-30). Nausea was encountered in 45 % of cases. At completion of OPAT, 1 patient (9 %) was cured, 2 (18 %) had improved and 8 (73 %) failed therapy. Failure occurred due to either progression or non-response of infection (n = 4), re-admission (n = 3), premature cessation of tigecycline due to nausea (n = 3) or death (n = 1). Whilst OPAT delivery of tigecycline is a therapeutic option, when used as second-line therapy for complex, often multi-resistant infections in patients with multiple comorbidities, high rates of clinical failure, readmissions and adverse effects, especially nausea, should be anticipated.

Topics: Administration, Intravenous; Adult; Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Drug Utilization; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tertiary Care Centers; Tigecycline; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Blood Coagulation Disorders; Critical Illness; Female; Fibrinogen; Humans; Male; Middle Aged; Minocycline; Partial Thromboplastin Time; Tigecycline

Tigecycline is an established treatment option for infections with multiresistant bacteria (MRB). It retains activity against many strains with limited susceptibility to other antibiotics. Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospective noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals.. Data on the full population have been published; our present analysis focuses on infections caused by MRB. The study population included patients with complicated infections, high disease severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had comorbidities, including cardiovascular disease, renal insufficiency, and/or diabetes mellitus. Treatment success was defined as cure/improvement without requirement of further antibiotic therapy.. Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE) and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB subpopulation, 140 patients received tigecycline monotherapy, 75 were treated with combination regimens. High overall clinical success rates were recorded for MRB infections treated with tigecycline alone (94 %) or in combinations (88 %); in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %), skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100 %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33 %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %).. Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity. These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Hospitalization; Humans; Intraabdominal Infections; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Prospective Studies; Tigecycline; Treatment Outcome; Vancomycin-Resistant Enterococci; Young Adult

The Tigecycline Evaluation and Surveillance Trial (TEST) is a global antimicrobial susceptibility surveillance study which has been ongoing since 2004. This report examines the in vitro activity of tigecycline and comparators against clinically important pathogens collected globally between 2004 and 2013.. Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute. The Cochran Armitage Trend Test was used to identify statistically significant changes in susceptibility between 2004 and 2013.. Among the Enterobacteriaceae susceptibility was highest to the carbapenems [imipenem 97.1% (24,655/25,381), meropenem 97.0% (90,714/93,518)], tigecycline (97.0%, 115,361/118,899) and amikacin (96.9%, 115,200/118,899). Against Acinetobacter baumannii the highest rates of susceptibility were for minocycline (84.5%, 14,178/16,778) and imipenem (80.0%, 3,037/3,795). The MIC90 for tigecycline was 2 mg/L. 40% (6,743/16,778) of A. baumannii isolates were multidrug-resistant. Enterococci were highly susceptible to tigecycline and linezolid (>99%); vancomycin resistance was observed among 2% of Enterococcus faecalis (325/14,615) and 35% of Enterococcus faecium (2,136/6,167) globally. 40% (14,647/36,448) of Staphylococcus aureus were methicillin-resistant while 15% (2,152/14,562) of Streptococcus pneumoniae were penicillin-resistant. Against S. aureus and S. pneumoniae susceptibility to linezolid, vancomycin, and tigecycline was ≥99.9%. Globally, 81% (331/410) of statistically significant susceptibility changes during the study period were decreases in susceptibility.. Amikacin, the carbapenems, and tigecycline were active against most gram-negative pathogens while linezolid, tigecycline, and vancomycin retained activity against most gram-positive pathogens collected in TEST during 2004-2013.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Evaluation; Drug Resistance, Bacterial; Epidemiological Monitoring; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Adolescent; Adult; Aged; Bacterial Infections; beta-Lactamases; Child; Child, Preschool; Escherichia coli; Female; Humans; India; Male; Middle Aged; Minocycline; Pseudomonas aeruginosa; Tertiary Care Centers; Tigecycline

Necrotizing skin and soft tissue infections (NSTI) form a group of aggressive diseases that require radical debridement for infection control. Simultaneously, a high-dose broad spectrum antibiotic regimen needs to be initiated with control of septic complications in the intensive care setting. The aim of this work is to analyze the efficacy and safety of tigecycline in a subpopulation of hospitalized, severely ill surgical NSTI patients who were documented in a large multicenter non-interventional study on tigecycline use in routine clinical practice.. A total of 1,025 patients with severe infections including complicated skin and soft-tissue infections (cSSTI, n=163; 15,9%) were enrolled in a prospective multi-center non-interventional study. Patients were to receive an initial intravenous dose of 100 mg tigecycline, followed by 50 mg twice daily. Prospectively documented parameters included clinical findings, APACHE II score, microbiological and standard laboratory assessments, surgical measures, and clinical outcomes including adverse events.. Of 163 patients were treated for cSSTI, with the largest subgroup being NSTI patients (n=50, 30.7% of all cSSTI, mean age 61 y, median APACHE II score 20). Forty-eight NSTI patients (96%) had at least one comorbidity. In 80% of patients, the treatment was started after previous antibiotic treatment had failed and in 34% resistant pathogens were isolated (28% methicillin resistant Staphyloccocus aureus [MRSA], 4% extended-spectrum-beta-lactamase (ESBL)-producing bacteria, and 2% vancomycin-resistant Enterococci (VRE). Tigecycline was administered as a single agent in 32 patients; 17 received combination regimens. Data from one patient were not reported. Rates of clinical cure or improvement with tigecycline treatment were 90.2%. Two patients (4%) had drug related adverse events (one thrombocytopenia and one fever/chills); 10 patients (20%) died.. Tigecycline alone or in combination therapy was an effective and safe antibiotic treatment in critically ill and antimicrobially pre-treated patients with NSTI frequently caused by resistant pathogens.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

To observe the curative effect and side effect of tigecycline in the treatment of patients with infection caused by granulocytopenia.. The clinical data of 107 patients who were treated with tigecycline for infection due to granulocytopenia were retrospectively reviewed. The tigecycline was administered by intravenously (30-60 min drip infusion)as the initial dose of 100 mg and maintenance does of 50 mg, every 12h. The whole treatment course kept for 5-7 d when the body temperature was normal and then the step-down treatment or discontinuation of the drug was adopted.. A total of 104 strains of bacteria were isolated from 107 cases of hospitalized patient, including 60 multi-drug resistant strains (MDR) and 2 extensively-drug resistant strains (XDR). The total effective rate of tigecycline treatment was 62.6%, including 30 cases with tigecycline alone (63.3% of the effective rate), 21 cases with tigecycline as initial treatment followed by combination with other antibiotics (61.9% of the effective rate), and 56 cases with tigecycline in combination with other antibiotics from the beginning of the treatment (62.5% of the effective rate). There was no statistical significant difference between the 3 treatment groups (P=0.994). Among the 39 patients with MDR strains, 22 patients' temperature was controlled , 9 patients died, and 8 patients' temperature remained uncontrolled. The clinical effective rate of these patients was 56.4%. The median onset time of tigecycline treatment was 3 days. The adverse drug reactions of nausea (11.2% ) and vomiting (8.4% )were tolerable.. Tigecycline is effective in treatment of resistant bacteria infection in patients with granulocytopenia. The side effects of tigecycline were few, safe and generally well tolerated.

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Body Temperature; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

We report, in a clinical setting, the tigecycline concentration and area under the concentration-time curve (AUC) - both in blood and in cerebrospinal fluid (CSF) - of a patient with a ventriculo-atrial shunt infection. Tigecycline weakly penetrates CSF the CSF-to-serum concentration ratio was 0.079 and CSF-to-serum AUC(0-12) ratio was 0.067.

Topics: Adult; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Female; Humans; Minocycline; Plasma; Tigecycline

Tigecycline is a relatively new glycylcycline antimicrobial, active in vitro against a variety of Gram-positive and Gram-negative organisms. In this study we evaluated the outcomes of spondylodiscitis cases treated with tigecycline-including therapies retrospectively.. All adult (age >18 years) cases with a diagnosis of spondylodiscitis, who were treated with a tigecycline-including therapy between 2007 and 2011, were included in the study. The primary efficacy outcome was clinical success with tigecycline at the end of induction, while the secondary efficacy outcome was maintenance of success through 3 months following completion of induction.. A total of eight spondylodiscitis cases fulfilled the study inclusion criteria. All cases had back pain, restricted mobility, magnetic resonance findings associated with spondylodiscitis, and microbiology or pathological findings related to spondylodiscitis. All had post-neurosurgical spondylodiscitis. In five cases, tigecycline was started in accordance with the antibacterial susceptibility results from intervertebral tissue biopsy cultures, whereas in three it was started empirically. All cases had received several different antibacterials with failure before receiving tigecycline. The mean duration of tigecycline treatment was 37±21 days. One case was lost to follow-up after 2 days of tigecycline. Primary and secondary success was achieved in the remaining seven cases.. These limited data suggest that tigecycline may have a role in the treatment of refractory spondylodiscitis cases.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Blood Sedimentation; C-Reactive Protein; Discitis; Disease Management; Female; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Neurosurgical Procedures; Postoperative Complications; Retrospective Studies; Tigecycline; Treatment Outcome

To evaluate the efficacy and safety of tigecycline in treating secondary infections of patients with hematological diseases.. A total of 85 cases of hematological patients with secondary infections were classified into empirical and targeted therapy groups. Empirical therapy group was composed of patients receiving tigecycline as an alternative due to ineffective anti-infection treatment for 3-5 days in the absence of microbiological evidence while those taking tigecycline based on microbiological evidence belonged to targeted therapy group. Dosage regimen of tigecycline: loading dose 100 mg, 50 mg every 12 hours as maintenance therapy for 2-4 weeks.. Among them, except for 11 cases of bloodstream infections and 2 cases of fever for unknown reasons, the most common site for infection was lower respiratory tract. Among 45 isolated bacterial strains, Stenotrophomonas maltophilia (40%) was the most commonly seen while extended spectrum beta-lactamases (ESBLS)+ multidrug resistant gram negative bacilli 15.6%. Among 5 bacterial strains, there were 3 methicillin-resistant Staphylococcus aureus+golden staphylococci strains and 2 excrement enterococci. The total effective rate of tigecycline was 72.9%. And the bacterial clearance rates of acinetobacter baumannii, ESBLS+ gram-negative bacillus and stenotrophomonas maltophilia were 85%, 70% and 55% respectively. The effect of tigecycline was equivalent for two groups. Pneumonia patients obtained an effective rate of 71%, compared to those with bloodstream infections (54.5%). For patients whose absolute neutrophil counts were less than 0.2 × 10⁹/L, the effective rate decreased obviously (45% vs 81.5%, P = 0.003). Adverse reaction was mild due to mostly gastrointestinal symptoms.. Tigecycline is a new treatment choice in treating secondary multidrug resistant infections of patients with hematological diseases. Empirical therapy of tigecycline may improve the therapeutic efficacy of patients non-responding favorably to conventional anti-infectives.

Topics: Bacterial Infections; beta-Lactamases; Gram-Negative Bacteria; Hematologic Diseases; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Tigecycline

This Supplement in the Journal of Antimicrobial Chemotherapy comprises a series of papers reporting on 'real-life' clinical experience with tigecycline. The data reported are derived from five European observational studies on the use of tigecycline, either as monotherapy or in combination with other antibiotics, for the treatment of complicated skin and soft-tissue infections or complicated intra-abdominal infections. Taken together, this collection of articles gives clinical insight into the use of tigecycline for the treatment of complicated infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Humans; Intraabdominal Infections; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Europe; Humans; Intraabdominal Infections; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

It is being increasingly recognised by clinicians and scientists that participants in randomised clinical trials (RCTs) of antibiotics of last resort do not represent the patients who will later be treated with these drugs. Data on this subject are limited and have not been investigated systematically. This observational study aimed to examine this hypothesis quantitatively, using the example of tigecycline. To evaluate the influence of recruitment, patients eligible for clinical trials were retrospectively compared with ineligible patients regarding baseline and clinical characteristics as well as outcome parameters, e.g. length of hospital stay, intensive care unit (ICU) stay, ventilation and mortality. The clinical characteristics of 187 patients illustrated differences in the nature and severity of disease, co-morbidities and outcome. Eligible and ineligible patients differed in a number of parameters, e.g. median APACHE II score (15.5 vs. 28.0), number of liver transplantations (5% vs. 18%; P=0.048), septic shock (21% vs. 49%; P=0.001), need for mechanical ventilation (30% vs. 79%; P<0.001), mean length of ICU stay (19.3 days vs. 40.7 days) and death (19% vs. 46%; P=0.001). Critically ill patients were under-represented in clinical trials. Moreover, only a minority of patients in clinical practice (13%) were potentially eligible for a pivotal RCT. The disparities likely result from strict exclusion criteria in RCTs and recruitment bias. These data emphasise the importance of including critically ill patients in RCTs of antibiotics against multiresistant bacteria in order to account for those who will later be treated.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Female; Humans; Male; Middle Aged; Minocycline; Patient Selection; Randomized Controlled Trials as Topic; Tigecycline; Treatment Outcome

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

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

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: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Incidence; Male; Middle Aged; Minocycline; Superinfection; Tigecycline; Young Adult

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug-Related Side Effects and Adverse Reactions; Humans; Minocycline; Tigecycline; Treatment Outcome; United States

As part of the Tigecycline Evaluation and Surveillance Trial (TEST), bacterial isolates were collected consecutively from centers globally between 2004 and 2009. MICs were determined locally using Clinical and Laboratory Standards Institute broth microdilution methodology. A total of 3114 anaerobic and 99,256 aerobic isolates were included in this study. The most active agents against Gram-negative anaerobes were metronidazole and meropenem (resistance ranges 0.0-0.5% and 0.0-0.9%, respectively); piperacillin-tazobactam was also active (resistance range 0.5-9.4%). Among Gram-positive anaerobes, resistance rates were lowest for meropenem, piperacillin-tazobactam, and metronidazole (ranges 0.0-0.5%, 0.0-1.8%, and 0.0-3.2% respectively). Tigecycline MIC(90) values for anaerobes ranged from 0.12 to 2 μg/mL. The most active antimicrobial agent against Gram-negative aerobes (excluding Pseudomonas aeruginosa) was tigecycline, with resistance ranging from <0.01% to 1.4%. Resistance was also low for imipenem (0.3-9.4%) and meropenem (0.7-15.1%). Extended-spectrum beta-lactamases were produced by 12.2% and 19.7% of E. coli and K. pneumoniae isolates, respectively.

Topics: Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Tigecycline

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

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

The aim of this study was to evaluate in vitro the antimicrobial efficacy of a modified 3-mix paste and to compare it with an iodoform paste (Ultrapex) against anaerobic microorganisms isolated from root canals of infected or necrotic primary teeth.. An in vitro experimental assay was performed over isolated and identified anaerobic microorganisms of 21 samples, in order to compare the antimicrobial ability of both root canal filling materials, using a disc-diffusion method.. A total of 21 microbial samples (15 polymicrobial and 6 monomicrobial) were obtained, from which 19 different strains were identified. Modified 3-mix paste showed an excellent antimicrobial effect against most of both kinds of microbial samples, although some of them exhibited resistance; on the other hand, Ultrapex showed only minimal antimicrobial ability (null or low categories). Clostridium ramosum exhibited the most resistance to both materials.. The bactericidal effect of the modified 3-mix paste was superior to Ultrapex, with a statistically significant difference, against anaerobic microorganisms isolated from infected root canals of primary teeth.

Topics: Actinomyces; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Bacteroides; Bifidobacterium; Calcium Hydroxide; Candida albicans; Ciprofloxacin; Clostridium; Dental Pulp Cavity; Dental Pulp Diseases; Dental Pulp Necrosis; Drug Combinations; Drug Resistance, Bacterial; Gemella; Humans; Materials Testing; Metronidazole; Microbial Sensitivity Tests; Minocycline; Prevotella melaninogenica; Propionibacterium acnes; Root Canal Filling Materials; Silicones; Streptococcus intermedius; Tooth, Deciduous

Topics: Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Male; Minocycline

Topics: Bacterial Infections; Humans; Minocycline; Tigecycline; United States; United States Food and Drug Administration

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and skin and skin structure infections and community-acquired bacterial pneumonia. Notwithstanding this, the tigecycline's pharmacological and microbiological profile encourage physicians' use of the drug in other infections. The aim of this study was to characterize the indications type, pathogens, and outcomes of patients who were treated with tigecycline. We analyzed the tigecycline prescriptions in 209 patients in 23 Latin American centres using an electronic form included in the website LatinUser (http://www.clinicalrec.com.ar). Sixty-six patients (31.5%) received tigecycline for approved indications, and 143 (68.5%) for "off label" indications (47% with scientific support and 21.5% with limited or without any scientific support). The most frequent "off label" use was ventilator-associated pneumonia (VAP) (76 patients). The etiology of infections was established in 88 patients (42%). Acinetobacter spp. (54.5%, in 65% of cases carbapenems-resistant), methicillin-resistant Staphylococcus aureus (12%), and extended spectrum β-lactamases-producing Enterobacteriaceae (10%) were the most common microorganisms isolated. Overall, attending physicians reported clinical success in 144 of the 209 patients (69%). Global mortality proportion was 35,5% (74/209 patients). Our study shows that the off label use of tigecycline is frequent, especially in VAP due to multidrug-resistant pathogens, where the therapeutic options are limited (eg: carbapenems-resistant Acinetobacter spp.). Physicians must evaluate the benefits/risks to use this antibiotic for indications that lack rigorous scientific support.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Child; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Internet; Male; Middle Aged; Minocycline; Off-Label Use; Pneumonia, Ventilator-Associated; Practice Patterns, Physicians'; Registries; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

With the increasing experience of tigecycline usage, its ecological impact on microorganisms raises concerns but remains unknown. We aimed to analyze the difference in microorganisms isolated before, during, and after tigecycline usage and their susceptibility to antimicrobial agents.. Between July 2008 and August 2009, 66 patients who received tigecycline monotherapy for more than 2 days at a Taiwan medical center were enrolled. Antimicrobial susceptibility testing was performed by broth microdilution method with VITEK-2 system and was analyzed according to the Clinical and Laboratory Standards Institute guidelines, except for tigecycline. We followed USA Food and Drug Administration criteria for interpretation of susceptibility to tigecycline.. The median duration of tigecycline monotherapy was 13.4 days. After tigecycline treatment, the isolation frequency of Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae decreased, but that of Pseudomonas aeruginosa, Proteus sp, and Stenotrophomonas maltophilia did not change. A baumannii and P aeruginosa were the two most common pathogens when tigecycline was administered. The tigecycline susceptibility rate of A baumannii isolates decreased after the administration of tigecycline.. The most common pathogens isolated in patients receiving tigecycline were A baumannii and P aeruginosa. Tigecycline usage decreased the isolation frequency of A baumannii, methicillin-resistant S aureus, E coli, and K pneumoniae. Exposure to tigecycline may be associated with a decreased susceptibility rate of A baumannii for tigecycline.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Taiwan; Tigecycline

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

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

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Meta-Analysis as Topic; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Minocycline

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Minocycline

The proinflammatory cytokine interleukin-1β (IL-1β) is critical for normal hippocampus (HP)-dependent cognition, whereas high levels can disrupt memory and are implicated in neurodegeneration. However, the cellular source of IL-1β during learning has not been shown, and little is known about the risk factors leading to cytokine dysregulation within the HP. We have reported that neonatal bacterial infection in rats leads to marked HP-dependent memory deficits in adulthood. However, deficits are only observed if unmasked by a subsequent immune challenge [lipopolysaccharide (LPS)] around the time of learning. These data implicate a long-term change within the immune system that, upon activation with the "second hit," LPS, acutely impacts the neural processes underlying memory. Indeed, inhibiting brain IL-1β before the LPS challenge prevents memory impairment in neonatally infected (NI) rats. We aimed to determine the cellular source of IL-1β during normal learning and thereby lend insight into the mechanism by which this cytokine is enduringly altered by early-life infection. We show for the first time that CD11b(+) enriched cells are the source of IL-1β during normal HP-dependent learning. CD11b(+) cells from NI rats are functionally sensitized within the adult HP and produce exaggerated IL-1β ex vivo compared with controls. However, an exaggerated IL-1β response in vivo requires LPS before learning. Moreover, preventing microglial activation during learning prevents memory impairment in NI rats, even following an LPS challenge. Thus, early-life events can significantly modulate normal learning-dependent cytokine activity within the HP, via a specific, enduring impact on brain microglial function.

Topics: Acoustic Stimulation; Animals; Animals, Newborn; Anti-Bacterial Agents; Bacterial Infections; Brain; CD11b Antigen; Conditioning, Classical; Cues; CX3C Chemokine Receptor 1; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Exploratory Behavior; Fear; Female; Flow Cytometry; Gene Expression Regulation; Glial Fibrillary Acidic Protein; In Vitro Techniques; Interleukin-1beta; Lipopolysaccharides; Male; Memory Disorders; Microglia; Minocycline; Neural Inhibition; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Chemokine; RNA, Messenger

MICs to tigecycline and 12 antimicrobials were performed by microdilution method, against 2423 nonduplicate pathogens recently isolated in 17 Greek hospitals. The Food and Drug Administration (FDA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria were used comparatively for interpretation of tigecycline MICs. Tigecycline exhibited potent in vitro activity against the majority of the isolates tested. (MIC(90) values of 0.5, 1, 2, 0.125, 1, 0.25, 0.125, and 1 mg/L were observed for Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Moraxella catarrhalis, Acinetobacter spp., Staphylococcus aureus, Enterococcus spp., and Streptococcus pneumoniae isolates, respectively.) Tigecycline activity was the same, irrespective of the resistance profile to other antimicrobials (Gram-negative pathogens susceptible or resistant to imipenem, Enterococcus spp., S. aureus, or S. pneumoniae isolates, susceptible or resistant to vancomycin, methicillin or penicillin, respectively). Interpretation using EUCAST and FDA breakpoints differed among isolates of K. pneumoniae and Enterobacter spp. having tigecycline MICs of 2 to 4 mg/L. In conclusion, tigecycline exhibited potent activity against pathogens recently isolated in a region that experiences high antimicrobial resistance rates. Indications that the available criteria might categorize differently tigecycline susceptibility status in K. pneumoniae and Enterobacter spp. isolates were also detected.

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

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

To test the activity of tigecycline against bacterial isolates including multi-drug resistant (MDR) gram negative and gram positive organisms from intensive care patients.. Clinically significant gram positive and MDR gram negative isolates from specimens of patients in the intensive care units of King Khalid University Hospital (KKUH), Riyadh, Kingdom of Saudi Arbia between November 1, 2006 and December 31, 2008 were tested against tigecycline by disc diffusion (DD) method. In some isolates, the minimal inhibitory concentration was carried out by E-test method. Some of the gram negative isolates, and gram positive isolates were tested using both methods. The study was approved by the hospital ethics committee.. All the 83 gram positive organisms tested by both DD and E-test were susceptible to tigecycline. Two hundred and fifty-four MDR gram negative isolates were tested for susceptibility to tigecycline. Of these 176 tested by DD, 159 (90%) were susceptible, 6 (3.4%) were resistant, and 11 (6.2%) were intermediately susceptible (data are not the same in table 3). From the 188 isolates tested by E-test, 140 (74.4%) were susceptible, 35 (18.6%) were resistant, and 13 (6.9%) showed intermediate susceptibility. For comparison between the methods, 109 isolates of the MDR gram negative organisms were tested by both E test and DD. The difference between the 2 methods was not significant.. Tigecycline was active against gram positive and most MDR gram negative isolates from patients in medical and surgical intensive cases in KKUH. There was no significant difference between the DD and E-test methods for susceptibility testing of tigecycline against these isolates.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Child; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitals, Teaching; Humans; Intensive Care Units; Minocycline; Saudi Arabia; Tigecycline

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; 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 broad spectrum antibiotic that is predominantly used for the treatment of severe infections both in critically ill patients admitted to the ICU and in non-ICU patients with less severe clinical conditions.. To assess differences in the use of tigecycline between ICU patients and non-ICU patients treated with this antibiotics.. Retrospective, cohort, observational study in which cases were defined as patients who received one or more doses of tigecycline over the first 18 months after approval of the drug in a general hospital. Clinical characteristics, indications, route of administration, clinical response, tolerability and outcome were recorded in the groups of ICU and non-ICU patients. Descriptive data and results of the comparison of both cohorts are presented.. A total of 103 were included in the study, 34(33%) of which received tigecycline during their stay in the ICU. ICU patients compared to non-ICU patients had a higher SAPS II score on admission (39.0 +/- 11.8 vs 26.3 +/- 8.0, p < 0.001) and at the time of starting tigecycline treatment (42.2 +/- 12.6 vs 25.6 +/- 8.2, p < 0.001), were treated with antibiotics for more days (21.4 +/- 30.6 vs 13.6 +/- 30.5 days, p < 0.012) and received a greater number of antibiotic agents concomitantly (85.3% vs 47.8%,p < 0.001), presented a higher selection of emerging bacterial flora (41.2% vs 15.9%, p =0.005), particularly Pseudomonas aeruginosa (20.6%vs 2.9%, p =0.006), higher rate of clinical failure (58.8%vs 21.7%, p < 0.001), longer hospitalization (51.2 +/- 39.4 vs 28.7 +/- 26.3 days, p < 0.001) and higher overall mortality rate (50% vs 14.5%, p < 0.001) and infection-attributed mortality (20.6% vs 7.2%, p =0.047).. The patient that receives tigecycline in the ICU has a higher severity level and worse clinical outcome than the non-ICU patient treated with this antibiotic. It is necessary to optimize the indications of tigecycline in the ICU to improve the clinical results.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Critical Care; Drug Utilization; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

Our aim was to determine the prevalence of multidrug resistance of Acinetobacter baumannii and other pathogens at a tertiary-care teaching hospital in Mexico over a 3-year period. Clinical isolates of A. baumannii (n = 550), Pseudomonas aeruginosa (n = 250), some Enterobacteriaceae species (n = 500) and Staphylococcus aureus (n = 250) collected over a 3-year period were included. Susceptibility tests were performed by the broth microdilution method. 74% of A. baumannii, 40% of Escherichia coli, 34% of P. aeruginosa, 22% of Klebsiella pneumoniae, 9% of Enterobacter cloacae, and 7% of Serratia sp. were multidrug resistant. 59% of A. baumannii clinical isolates were meropenem-resistant. A. baumannii isolates from the lower respiratory tract were the most susceptible, followed by urine clinical isolates. Species from Enterobacteriaceae showed susceptibility rates higher than 90% to meropenem and tigecycline and Serratia sp. showed the highest susceptibility to the drugs evaluated. For P. aeruginosa, the most potent drug was levofloxacin, followed by meropenem and piperacillin-tazobactam. With regard to S. aureus, 96% of the isolates were susceptible to vancomycin, followed by tigecycline and minocycline (91% of strains susceptible). The high multidrug resistance observed underscores the need for surveillance of bacterial drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Hospitals, Teaching; Humans; Klebsiella pneumoniae; Meropenem; Mexico; Microbial Sensitivity Tests; Minocycline; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcus aureus; Thienamycins; Tigecycline

This study investigated the effect of different Mueller-Hinton agars and media age on tigecycline MICs, obtained by Etest. Variations in MIC values on different Mueller-Hinton were noted, which may result in changes in categoric susceptibility. The use of stored Mueller-Hinton media had minimal effect on MIC values.

Topics: Acinetobacter; Agar; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Culture Media; Enterobacteriaceae; Humans; Microbial Sensitivity Tests; Minocycline; Staphylococcus aureus; Tigecycline; Time Factors

Tigecycline belongs to a new class of antimicrobial agents, the glycylcyclines, which are structurally derived from tetracyclines. It is effective against both gram positive and gram negative bacteria, aerobes and anaerobes and bacteria that have developed resistance against the classic tetracyclines. Although there is an increased risk for serious adverse events, tigecycline is important for treatment of patients with complicated infections of moderate severity where other antimicrobials cannot be used.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Minocycline; Tigecycline

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Male; Middle Aged; Minocycline; Prescriptions; Retrospective Studies; Tigecycline; Treatment Outcome

Cancer patients with complicated infections following abdominal surgery represent one of the worst clinical scenarios that is useful for testing the efficacy of empirical antimicrobial therapy. No study so far has evaluated the performance of tigecycline (TIG) when administered as empirical first-line treatment in a homogeneous population of surgical cancer patients with a febrile episode. An observational review of the data records of 24 sequential patients receiving TIG for a febrile episode following a major abdominal procedure in a single cancer institute was performed. Large bowel surgery represented 68% of all procedures, followed by gastric surgery (16%) and urinary-gynaecologic-biliary surgery (16%). Complications following surgery were observed in 68% of febrile episodes, with peritonitis and sepsis accounting for 59% and 24% of complications, respectively. Eight patients needed repeat surgery for source control. The mean duration of TIG treatment was 8 days. Causative pathogens were detected in 16 episodes (64%), and a total of 44 microorganisms were recovered (29% Escherichia coli, 9% Enterococcus faecalis and 9% coagulase-negative staphylococci). TIG was effective in 12 episodes (48%). The success rate was 67% when infectious episodes sustained by intrinsically resistant bacteria and fungi were excluded. Treatment failure was associated with the presence of complications and with microbiologically documented infection. TIG may be useful as a first-line treatment option in cancer patients requiring antibiotic treatment following surgery when complications are not present or suspected on clinical grounds and when local microbial epidemiology shows a low incidence of primary resistant bacteria.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Enterococcus faecalis; Escherichia coli; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Minocycline; Neoplasms; Peritonitis; Sepsis; Staphylococcus; Surgical Wound Infection; Tigecycline; Treatment Outcome

The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacterial Infections; Computational Biology; Daptomycin; Drug Delivery Systems; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Forecasting; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Linezolid; Minocycline; Oxazolidinones; Pharmacogenetics; Systems Biology; Tigecycline; Virginiamycin

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

The aim of this study was to determine the economic impact on hospital budget expenditure for two different prescribing practices: use of tigecycline in second or first-line therapy (when appropriate). This empirical study was carried out at the Intensive Care Unit (ICU) (Chief, Dr. Alberto Costantini), Ospedali Riuniti, Ancona. Cost determination was based on health care processes as revealed by field survey at the ICU. Mapping of the health care processes was neither derived from official protocols nor from an ex-post analysis of medical records but rather directly from descriptions of the processes as referred by the ICU physicians and health care staff, and then summarized in flow charts and approved by the ICU chief. The assumption was that tigecycline, because of its broader spectrum of action, would more probably clear infections when used in the first course of antibiotic therapy. Notwithstanding this advantage, tigecycline has a higher daily dose cost than first-line antibiotics. This study compared the higher costs incurred by the use of tigecycline as a first-line antibiotic versus potential savings obtained with such use, also in view of the prevention of possible treatment failures and the additional cost of administering a second course of antibiotic therapy, wherein the result would depend on the number of preventable treatment failures. The analysis concludes with a discussion and graphic illustrations comparing the differential probable treatment success which would render the two treatment alternatives economically indifferent.

Topics: Abdomen; Algorithms; Anti-Bacterial Agents; Bacterial Infections; Cost-Benefit Analysis; Humans; Intensive Care Units; Italy; Minocycline; Tigecycline

Tigecycline is a broad spectrum antibiotic indicated by official and health ministry guidelines for use in second course therapy for complicated intra-abdominal infections (cIAI). In certain objective and subjective circumstances, however, its use in first-line therapy may be appropriate. Without entering into a detailed evaluation of use appropriateness, the aim of this study was to determine the economic impact on hospital budget expenditure for two different prescribing practices: use of tigecycline in second or first-line therapy. This empirical study was carried out at the Intensive Care Unit (ICU) (chief, Dr. Alberto Costantini), Ospedali Riuniti, Ancona.. Cost determination was based on health care processes as revealed by field survey at the ICU. Mapping of the health care processes was not derived from official protocols or from an ex post analysis of medical records but rather directly from descriptions of the processes as referred by the ICU physicians and health care staff, and then summarized in flow charts and approved by the ICU chief.. The assumption was that tigecycline, because it has a broader spectrum of action than a first-line antibiotic, would more probably clear infections when used in the first course of antibiotic therapy. Notwithstanding this advantage, tigecycline has a higher daily dose cost than first-line antibiotics. This study compared the higher costs incurred by the use of tigecycline as a first-line antibiotic versus potential savings obtained with such use, also in view of the prevention of possible treatment failures and the additional cost of administering a second course of antibiotic therapy, wherein the result would depend on the number of preventable treatment failures.. The analysis concludes with a discussion and graphic illustrations comparing the differential probable treatment success which would render the two treatment alternatives economically indifferent.

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Protocols; Cost-Benefit Analysis; Critical Care; Drug Costs; Hospital Costs; Humans; Intensive Care Units; Length of Stay; Minocycline; Retreatment; Tigecycline; Treatment Outcome

We assessed the adherence to the prescribing hospital protocol for tigecycline and factors associated with noncompliance. A total of 103 patients were included in the study. In 23 (22.3%) patients, tigecycline was not administered according to the protocol, mostly because of the availability of other therapeutic alternatives and prescription for indications that were not included in the guidelines. factors independently associated with nonadherence to the protocol were community-acquired infection (OR, 14.01; 95% CI, 1.54-127.12; P=0.019), and empirical tigecycline treatment (OR, 6.97; 95% CI, 0.88-55.40; P=0.066). penicillin allergy (OR, 0.004; 95% CI, 0.000-0.071; P=0.001) and previous antibiotic treatment (OR, 0.025; 95% CI, 0.003-0.233; P=0.001) were factors associated with adherence to the hospital protocol. A positive time trend between total number of prescriptions and non-compliant prescriptions with the protocol was observed (Spearman's rho coefficient 0.971; P=0.001). Adherence to tigecycline protocol could be improved by focusing on protocols for community-acquired infections, mainly skin and soft tissue infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactam Resistance; Clinical Protocols; Community-Acquired Infections; Drug Hypersensitivity; Female; Guideline Adherence; Hospitals, University; Humans; Male; Medical Order Entry Systems; Minocycline; Penicillins; Practice Guidelines as Topic; Retrospective Studies; Tigecycline; Treatment Outcome

In concert with the development of novel beta-lactams and broad-spectrum cephalosporins, bacterially encoded beta-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-beta-lactamase (ESBL) phenotypes of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates collected during the global tigecycline phase 3 clinical trials. PCR assays were developed to identify and clone the bla(TEM), bla(SHV), bla(OXA), and bla(CTX) genes from clinical strains. Isolates were also screened for AmpC genes of the bla(CMY), bla(ACT), bla(FOX), and bla(DHA) families as well as the bla(KPC) genes encoding class A carbapenemases. E. coli, K. pneumoniae, and P. mirabilis isolates with ceftazidime MICs of > or =2 microg/ml were designated possible ESBL-producing pathogens and were then subjected to a confirmatory test for ESBLs by use of Etest. Of 272 unique patient isolates, 239 were confirmed by PCR and sequencing to carry the genes for at least one ESBL, with 44% of the positive isolates harboring the genes for multiple ESBLs. In agreement with current trends for ESBL distribution, bla(CTX-M)-type beta-lactamase genes were found in 83% and 71% of the ESBL-positive E. coli and K. pneumoniae isolates, respectively, whereas bla(SHV) genes were found in 41% and 28% of the ESBL-positive K. pneumoniae and E. coli isolates, respectively. Ninety-seven percent of the E. coli and K. pneumoniae isolates were tigecycline susceptible (MIC(90) = 2 microg/ml), warranting further studies to define the therapeutic utility of tigecycline against strains producing ESBLs in a clinical setting.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Clinical Trials, Phase III as Topic; DNA Primers; Drug Resistance, Bacterial; Escherichia coli; Humans; Isoelectric Focusing; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Proteus mirabilis; Reverse Transcriptase Polymerase Chain Reaction; Tigecycline

Tigecycline is a novel antimicrobial agent for parenteral use encompassing a broad spectrum of bacterial pathogens, including multi-resistant organisms. Here, we report the results of the first nationwide surveillance trial that was conducted in order to evaluate the susceptibility of bacterial isolates to tigecycline in a European country prior to its clinical use. A total of 2,610 Gram-positive and Gram-negative organisms recovered from hospitalized patients were tested. Minimum inhibitory concentrations (MICs) were determined using the microdilution method. All enterococci, staphylococci (including methicillin-resistant Staphylococcus aureus; MRSA), and streptococci tested were tigecycline-susceptible, except one isolate of Staphylococcus haemolyticus. Among the Gram-negative bacteria, 100% of the Escherichia coli isolates (including extended spectrum beta-lactamase [ESBL]-producers) were tigecycline-susceptible, while about 10% of the Enterobacter cloacae and Klebsiella pneumoniae isolates were resistant. Based on the results of this surveillance study, tigecycline may represent a suitable option most notably for the empiric treatment of bacterial mixed infections, including in clinical situations in which multi-resistant organisms are suspected.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Aerobic; Bacterial Infections; Child; Child, Preschool; Female; Germany; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Tigecycline (TGC), a semisynthetic glycylcycline, has a documented activity on Gram+ and Gram- pathogens including oxacillin-resistant (MRSA) and an extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of TGC and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The aim of this study was to assess efficacy of TGC, using this database, against pathogens implicated in community or hospital pneumonia and sinusitis. A total of 4163 isolates were consecutively collected in 21 European countries during three years (2004-2007). In all center, minimum inhibitory concentration (MIC) were determinated with the same Microscan panel (Dade-Behring). Tigecycline exhibited a good activity against respiratory pathogens, with the exception of Pseudomonas aeruginosa. Hundred percent of cocci Gram+ (Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus sp.) and 100% of Haemophilus sp. are inhibited with 0.5 mg/L, without effect of an associated beta-lactam resistance mechanism. TGC is active in vitro on 89% of Enterobacteriaceae, with MIC 90 less or equal to 2mg/L. Eighty-nine percent of Enterobacter sp. and 77% of Serratia sp. are susceptible with range of MIC 90 from 2 to 4 mg/L. These interesting results obtained in vitro are to be strengthened by clinical studies.

Topics: Bacteria; Bacterial Infections; Bronchoalveolar Lavage Fluid; Drug Evaluation; Drug Resistance, Microbial; Enterobacteriaceae; Europe; Haemophilus; Humans; In Vitro Techniques; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Respiratory Tract Infections; Species Specificity; Streptococcus pneumoniae; Tigecycline

Tigecycline, a broad-spectrum antibiotic for parenteral use, was introduced in Germany in May 2006. In the G-TEST-II trial, the susceptibility of isolates, recovered in 2007 from hospitalised patients in 15 centres, was assessed against tigecycline and comparators. Susceptibility tests were performed by the microdilution procedure. This study reports on the susceptibility of the isolates of 16 bacterial species and compares the results with those of a trial (G-TEST I) conducted prior to the introduction of tigecycline. Between 2005 and 2007, tigecycline retained activity against Gram-positive and Gram-negative organisms. By contrast, the rate of vancomycin-resistant strains among Enterococcus faecium isolates almost doubled. Moreover, an increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for members of the family Enterobacteriaceae. Against a background of a steadily rising number of pathogens that are resistant to various antibiotic classes, tigecycline represents an important treatment option.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Germany; Hospitals; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Young Adult

Tigecycline, the first in a new class of glycylcyclines, has been approved for the treatment of complicated skin and skin structure and intraabdominal infections in adults. However, clinical data on its safety and effectiveness in cancer patients are lacking. We reviewed the records of all cancer patients treated with tigecycline for more than 48 hours between June 2005 and September 2006 at our institution and identified 110 consecutive cases (median age, 58 yr; range, 18-81 yr). We collected data on demographics, cancer type, tigecycline indication, microbiologic characteristics, side effects, and outcome. Sixty-four (58%) patients had hematologic malignancies; 27 patients had undergone hematopoietic stem cell transplantation. Thirty-one (28%) patients had neutropenia, and 62 (56%) were in the intensive care unit at the start of therapy. Most patients (106 [96%]) received tigecycline as a second-line agent (after not responding to other broad-spectrum antibiotics), and 101 (92%) received it in combination with an antipseudomonal drug. The mean duration of therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had intraabdominal infections, and 7 (6%) had complicated skin and soft tissue infections. Fifty (45%) patients had microbiologically documented infections, and the remaining patients had negative cultures at the start of therapy.An overall clinical response was noted in 70 (64%) patients. More clinical responses were seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p = 0.029). Patients with microbiologically documented infections had significantly higher clinical response rates than patients with non-microbiologically documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not respond to treatment; 36 of these patients died of active infection during tigecycline therapy. Patients with pneumonia had a significantly higher mortality rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days of follow-up from the date of clinical response, patients with pneumonia had significantly shorter survival durations than patients with other infections. Of the 42 patients who were not on antiemetics or ventilator support at the start of tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during tigecycline therapy, all

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Female; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Leukemia; Lymphoma; Male; Middle Aged; Minocycline; Nausea; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome; Vomiting; Young Adult

Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires limitation of vitamin D in order to avoid contributing to dysfunction of nuclear receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Reactive; Arthritis, Rheumatoid; Autoimmune Diseases; Bacterial Infections; Calcifediol; Calcitriol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Imidazoles; Minocycline; Psoriasis; Receptors, Calcitriol; Sarcoidosis; Scleroderma, Systemic; Sjogren's Syndrome; Spondylitis, Ankylosing; Tetrazoles; Thyroid Diseases; Uveitis

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Hospitals; Humans; Inpatients; Latin America; Minocycline; Off-Label Use; Tigecycline; Treatment Outcome

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

Tigecycline is a novel antimicrobial agent recently licensed in the United Kingdom (UK), United States and Europe. It is a broad spectrum glycylcycline antibiotic which has structural similarities to the tetracyclines but is more potent against tetracycline-resistant organisms. It is only available as an intravenous (IV) preparation. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of tigecycline. The article also discusses the warnings and precautions associated with the use of this drug. Tigecycline may be used for complicated intra-abdominal and complicated skin and soft tissue infections. It is also likely to find a role in the treatment of infections caused by multi-resistant organisms such as Acinetobacter species.

Topics: Anti-Bacterial Agents; Bacterial Infections; Critical Care; Critical Illness; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Europe; Humans; Microbial Sensitivity Tests; Minocycline; Patient Selection; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; United Kingdom; United States

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Topics: Abdominal Cavity; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Labeling; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Tigecycline; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Minocycline; Taiwan; Tigecycline

A 63-year-old man who had undergone Miles' operation for rectal cancer in another hospital was referred due to a high fever and renal failure. Abdominal computed tomographic (CT) scan revealed metastatic liver tumor, paraaortic lymph node swelling, bilateral hydronephrosis and a left simple renal cyst located at the lower pole. Bilateral ureteral stenting was undertaken for relieving ureteral obstruction. Serum creatinine and high fever improved immediately. However, at 11 days after the ureteral stenting the high fever recurred. CT scan and ultrasonography revealed persistent left hydronephrosis and a change of left simple renal cyst into infected cyst. After an exchange of left ureteral stent and percutaneous pus drainage from the left infected renal cyst, high fever declined immediately. A review of the literature suggests that this is the 100th case report of infected renal cyst in Japan. We discuss the clinical features, etiology, imaging study and treatment of infected renal cyst.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Hydronephrosis; Kidney Diseases, Cystic; Male; Middle Aged; Minocycline; Radiography, Abdominal; Tomography, X-Ray Computed; Ultrasonography; Ureteral Obstruction

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Tigecycline

We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactamases; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial; Haemophilus influenzae; Hospitals; Humans; Minocycline; Moraxella catarrhalis; Phenotype; Streptococcus pneumoniae; Taiwan; Tigecycline

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Clinical Trials as Topic; Humans; Microbial Sensitivity Tests; Minocycline; Species Specificity; Tigecycline

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Minocycline; Skin Diseases, Bacterial; Tigecycline; United Kingdom

The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 countries worldwide, involved patients with complicated skin and skin-structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, < or =2 microg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated skin and skin-structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated skin and skin-structure infections or complicated intra-abdominal infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials, Phase III as Topic; Drug Resistance, Multiple, Bacterial; Humans; Intestinal Diseases; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Tigecycline

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

To evaluate the clinical outcome of 'Lesion Sterilization and Tissue Repair' (LSTR) therapy for endodontic treatment of primary teeth.. A mixture of metronidazole, ciprofloxacin, and minocycline (3Mix) in ointment (macrogol mixed with propylene glycol: MP) or in a root canal sealer was used to disinfect infected root canals of 56 patients aged 4-18 years. Out of a total of 87 primary teeth, 81 cases had physiologic root resorption. A total of 54 radiolucent periradicular lesions were present. The root canals were not prepared before or after disinfection. 3Mix medicament (3Mix-MP/3Mix-sealer) was placed at orifices of root canals or on the bottom of pulp chambers, and then sealed with glass-ionomer cement and further reinforced by a composite resin inlay prepared using a direct method and cemented with resin.. In all cases, clinical symptoms such as gingival swelling (52 cases), sinus tracts (22 cases), induced dull pain (3 cases), spontaneous dull pain (26 cases), and pain on biting (46 cases) disappeared after treatment, although in four cases clinical signs and symptoms were finally resolved only after retreatment using the same procedures. Thus, gingival abscesses and fistulae, if present, disappeared after a few days. Successor permanent teeth erupted without any disorders, or were found radiographically to be normal and in the process of eruption. All the cases were evaluated as successful. The mean function time of the primary teeth was 680 days (range: 68-2390 days), except for one case in which the successor permanent tooth was congenitally missing.. Primary teeth with periradicular lesions with or without physiologic root resorption were treated successfully by the LSTR endodontic therapy.

Topics: Adolescent; Anti-Infective Agents, Local; Bacterial Infections; Child; Child, Preschool; Ciprofloxacin; Dental Pulp Diseases; Drug Combinations; Humans; Metronidazole; Minocycline; Ointments; Root Canal Filling Materials; Root Canal Therapy; Tooth, Deciduous

The antimicrobial activities of tigecycline (GAR-936) were compared with those of other agents against 1,087 strains recently isolated in 12 Spanish medical centers. Tigecycline showed activity against a wide spectrum of aerobic and anaerobic bacteria, including strains such as methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant Streptococcus pneumoniae, Enterococcus faecium, Acinetobacter baumannii, and Stenotrophomonas maltophilia.

Topics: Anti-Bacterial Agents; Bacteria; Bacteria, Anaerobic; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Minocycline; Penicillin Resistance; Spain; Tigecycline

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

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

The aim of this study was to obtain information for an effective antimicrobial therapy against orofacial odontogenic infections; such information was obtained from recent bacteriologic features and antimicrobial susceptibility data.. The bacteriology and antimicrobial susceptibility of major pathogens in 163 patients with orofacial odontogenic infections to 7 antibiotics was examined.. Mixed infection of strict anaerobes with facultative anaerobes (especially viridans streptococci) was observed most often in dentoalveolar infections, periodontitis, and pericoronitis. Penicillin (penicillin G) was effective against almost all pathogens, although it did not work well against beta-lactamase-positive Prevotella. Cefmetazole was effective against all test pathogens. Erythromycin was ineffective against viridans streptococci and most Fusobacterium. Clindamycin exerted a strong antimicrobial activity on anaerobes. Minocycline was effective against almost all the test pathogens. The antimicrobial activity of levofloxacin against viridans streptococci was not strong.. An antibiotic that carries out antimicrobial activity against both viridans streptococci and oral anaerobes should be suitable for treatment of dentoalveolar infection, periodontitis, and pericoronitis. Penicillin remains effective as an antimicrobial against most major pathogens in orofacial odontogenic infections. Cefmetazole, clindamycin, and minocycline may be effective against most pathogens, including penicillin-unsusceptible bacteria.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamases; Cefmetazole; Chi-Square Distribution; Clindamycin; Drug Resistance, Microbial; Erythromycin; Humans; Microbial Sensitivity Tests; Minocycline; Mouth Diseases; Penicillins; Periapical Abscess; Pericoronitis; Periodontal Abscess; Periodontitis; Prevotella; Streptococcus

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

Topics: Aged; Aged, 80 and over; Aging; Anti-Bacterial Agents; Bacterial Infections; Body Weight; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Male; Minocycline; Respiratory Tract Infections; Statistics as Topic; Time Factors

To report changes in the white blood cell (WBC) counts in expressed prostatic secretions (EPS) in men with pelvic symptoms undergoing thrice-weekly prostatic massage combined with antimicrobial therapy.. The study comprised a retrospective analysis of the records of 35 patients (mean age 45.3 years, range 28-70, SD, 12.03) with pelvic pain, pain in the lower back, obstructive urinary symptoms, irritative urinary symptoms, or sexual dysfunction, who had undergone the same diagnosis and treatment protocol in a genitourinary clinic in Manila, Philippines, from September 1992 to September 1995.. EPS were obtained 347 times in 35 patients (median 9 times per patient, range 6-16). In 26 of the 35 (74%) patients the WBC count in the EPS was < 10 per oil-immersion field (OIF, x1000) at the first prostatic massage. In 34 of 35 (97%) patients the WBC count rose to > or = 10 as prostatic massage continued on a thrice-weekly schedule. The mean (range, SD) initial WBC count in the EPS was 8.4 (1-48, 8.43) and the maximum was 40.9 (6-60, 19.05); the difference between these values was 32.5 (3-57, 18.78; 95% confidence interval 26.1-40.1) and the difference was statistically significant (paired t-test, P < 0.001).. The classification of patients into those with prostatodynia or prostatitis based on one EPS examination is misleading and thrice-weekly massage of the prostate is better than a single collection of EPS to obtain the most purulent sample for Gram staining and culture.

Topics: Adult; Aged; Anti-Infective Agents, Urinary; Antibiotics, Antineoplastic; Bacterial Infections; Drug Therapy, Combination; Humans; Leukocyte Count; Low Back Pain; Male; Massage; Middle Aged; Minocycline; Ofloxacin; Pain; Pelvic Pain; Prostatitis; Retrospective Studies; Sexual Dysfunction, Physiological; Urinary Retention

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

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

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Bacterial Infections; Double-Blind Method; Drug Combinations; Humans; Methotrexate; Minocycline; Organogold Compounds; Placebos; Randomized Controlled Trials as Topic

Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary tract infections (UTIs) in 11 hospitals during June 1992 to May 1993 to various antimicrobial agents were compared with those in the same period of previous years according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. The susceptibilities of E. faecalis isolated from uncomplicated UTIs to quinolones has decreased. As for S. aureus, Citrobacter spp., Enterobacter spp., P. mirabilis and Serratia spp., which were detected very few in 1989, 1990, 1991 and 1992, their susceptibilities were not observed an obvious change. E. coli, all strains were highly susceptibilities to latamoxef and cefozopran. And the susceptibilities of E. coli isolated from uncomplicated UTIs and complicated UTIs without indwelling catheter to minocycline has decreased in 1991, but they has been indicated a trend of recovery in 1992. The difference in according UTI's classification of the susceptibilities of Klebsiella spp. to minocycline in 1991 has not recognized in 1992. And the susceptibilities of Klebsiella spp. isolated from complicated UTIs without indwelling catheter to quinolones has decreased. The susceptibilities of P. aeruginosa isolated from complicated UTIs to quinolones has been indicated a trend of recovery. These data should be considered in clinical treatment of various urinary tract infections.

Topics: 4-Quinolones; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacterial Infections; Catheters, Indwelling; Enterococcus faecalis; Escherichia coli; Humans; Klebsiella; Microbial Sensitivity Tests; Minocycline; Urinary Catheterization; Urinary Tract Infections

The present study was carried out to examine the distribution of six periodontopathic bacteria in deep periodontal pockets and to reconfirm the effect of Periocline on these periodontopathic bacteria. Samples from sixty-two periodontal pockets were collected at pocket depths of over 4 mm in twenty-one periodontitis patients aged 43 to 75 years. After sampling, Periocline was applied topically to the selected pockets once a week for four weeks and reexamined. The detected rates of the periodontopathic bacteria were Capnocytophaga sputigena (37.1%), Prevotella intermedia (22.6%), Porphyromonas gingivalis (22.6%), Fusobacterium nucleatum (20.1%), Actinobacillus actinomycetemcomitans (9.7%) and Eikenella corrodens (4.8%). The distribution of the bacteria was compound because two or three bacterial species were found to coexist. In view of the MIC of minocycline-HCI for these bacteria, increase of most of the measured bacteria was suppressed by the concentration of drugs, including Periocline. However, clinical strains of P. i. were considered to have low susceptibility to minocycline-HCl. In view of the effect of topical application of drugs, no significant differences were found. From these results, it was suggested that Periocline contained effective concentration of minocycline-HCl.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Female; Humans; Male; Middle Aged; Minocycline; Periodontal Pocket; Periodontitis; Tetracycline Resistance

Tightly coiled spiral micro-organisms (Gastrospirillum hominis), distinct from Helicobacter pylori, were found in the gastric mucosa of a 66-year-old man with a 4-month history of intermittent epigastric pain. The organisms were distributed in the antral mucosa, which showed erosive gastritis; histologically, the affected mucosa presented moderate to severe chronic gastritis with focal neutrophil infiltration. After a 2-week administration of cimetidine, his symptoms resolved and the active inflammation was reduced, both endoscopically and histologically, but the organisms still remained. Biopsy specimens taken 4 weeks after treatment with minocycline and cimetidine showed normal gastric mucosa without the spiral organisms. The above clinical course suggests the possible role of Gastrospirillum hominis in the pathogenesis of gastritis.

Topics: Aged; Bacterial Infections; Cimetidine; Gastric Mucosa; Gastritis; Helicobacter heilmannii; Humans; Japan; Male; Minocycline

We evaluated clinical effects and toxicities of a combination in treatment with cefodizime (CDZM) and minocycline (MINO) for infections complicated with hematological disorders in 67 patients. Fifty-nine patients were evaluable, including 32 with acute leukemia, 15 with malignant lymphoma, and 12 with other hematological disorders. Clinical efficacies were excellent in 17 cases, good in 24 cases, fair in 2 cases, and poor in 16 cases. The efficacy rate was 69.5% (41 cases/59 cases). This treatment was also effective in 8 of 12 cases in which granulocyte counts were less than 500/microliter through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 5 cases. Mild elevations of GOT, GPT, Al-P and bilirubin were observed, but none was serious. Thus, the combination of CDZM and MINO is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.

Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Aspartate Aminotransferases; Bacterial Infections; Cefotaxime; Drug Evaluation; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline

This study was designed to investigate whether antibiotic resistant micro-organisms are able to contaminate and survive on syringe tips used for subgingival deposition of antibiotics, and to test simple and effective means of disinfecting the syringe tip between applications. In the first part of the study, syringe tips used for application of Minocycline subgingival formula in 20 adult periodontitis patients were cultured for bacteria resistant to this drug before and after disinfecting them with ethanol. The results showed that 80% of the unwashed syringes were culture positive for minocycline resistant bacteria, whereas only 1 ethanol washed syringe tip was contaminated. In part II of the study, after dispensing minocycline periodontal formula in 20 patients, 10 of the syringe tips were washed with ethanol while 10 were left untreated. All syringes were stored in a refrigerator for 8 days, whereafter the tips were sampled for resistant bacteria. 20% of the unwashed tips were contaminated after 8 days incubation at 4 degrees C. None of the ethanol washed syringe tips were culture positive. We conclude that syringe tips may be contaminated with antibiotic resistant bacteria after dispensing the antibiotic in periodontal pockets. The transmission of these bacteria to other periodontal sites may be avoided by disinfecting the syringe tip with ethanol between applications. We have also shown that antibiotic resistant bacteria may survive on the syringe tip following 8 days storage in a refrigerator, suggesting that syringes used for subgingival deposition of an antibiotic should not be stored for reuse.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cold Temperature; Colony Count, Microbial; Disinfection; Disposable Equipment; Equipment Contamination; Ethanol; Female; Humans; Infection Control; Male; Middle Aged; Minocycline; Periodontal Pocket; Syringes; Tetracycline Resistance

Using pharyngeal epithelial cells from a healthy adult and eight strains of Branhamella catarrhalis (B. catarrhalis) isolated from eight patients with respiratory infection the effect of subminimal inhibitory concentrations of cefmetazole, ampicillin and minocycline on adherence was examined. Cefmetazole-treated bacterial attachment (44 +/- 28; mean +/- S.D.) decreased significantly (p less than 0.05) compared to the control (84 +/- 27). Statistically no significant difference in adherence was found between ampicillin-treated bacteria (63 +/- 36) and the control (95 +/- 40) or minocycline-treated bacteria (91 +/- 39) and the control (109 +/- 40). Large bacteria was observed after cefmetazole and ampicillin treatment. In addition to diplococci, tetrads were observed after cefmetazole treatment. Significant correlation between the MICs and adherence ability was not found. The results suggests that these three antibiotics were not responsible for the increase in B. catarrhalis infection by increasing adherence ability.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Infections; Cefmetazole; Epithelium; Humans; In Vitro Techniques; Minocycline; Moraxella catarrhalis; Pharynx; Respiratory Tract Infections

Topics: Acute Disease; Adult; Amoxicillin; Bacterial Infections; Child, Preschool; Humans; Minocycline; Sinusitis

Minocycline prophylaxis was compared with a placebo in 126 consecutive patients undergoing hysterectomy. The double-blind nature of this study was guarded until the study was completed. Of 95 patients who had abdominal hysterectomies, 32.7% on minocycline and 39.1% on placebo developed infectious complications. Of 31 vaginal hysterectomy patients, 20% on minocycline and 37.5% on the placebo developed septic complications (p less than 0.05). Although minocycline inhibited B. fragilis and E. coli effectively, those organisms colonized increasingly during the postoperative period with similar frequency in both the minocycline- and placebo-treated groups. Minocycline did not produce antibiotic-resistant strains. In our study the parenteral and oral forms of minocycline were found to be safe, and vestibular symptoms were no more common than in the placebo group. These data suggest that antibiotic prophylaxis with minocycline is safe and well tolerated. In addition, minocycline is effective in lowering the infection rate in vaginal, but not abdominal, hysterectomies.

Topics: Bacterial Infections; Double-Blind Method; Female; Humans; Hysterectomy; Hysterectomy, Vaginal; Microbial Sensitivity Tests; Minocycline; Postoperative Complications; Premedication; Random Allocation; Tetracyclines

The minimal inhibitory concentration (MIC) of Propionibacterium acnes in seventy-five acne patients receiving long-term antibiotic therapy demonstrated the emergence of resistant strains. The mean MIC in thirty-three patients receiving long-term tetracycline was four to five times higher than that found in control groups of acne patients not receiving antibiotic therapy and controls free of acne. The average MIC for erythromycin was more than 100 times higher in those receiving long-term antibiotic therapy. In a second group of sixty-two patients, the clinical course and number of P. acnes were correlated with the presence of "resistant strains" defined as P. acnes with a tenfold increase in MIC to tetracycline or erythromycin. Patients with resistant strains had higher counts of P. acnes and clinically were not doing as well as those with sensitive strains.

Topics: Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Drug Resistance, Microbial; Erythromycin; Female; Humans; Male; Minocycline; Propionibacterium acnes; Tetracycline

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

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

Topics: Acute Disease; Adult; Aged; Anemia, Aplastic; Bacterial Infections; Carbenicillin; Cefazolin; Female; Humans; Infusions, Parenteral; Leukemia; Male; Middle Aged; Minocycline; Multiple Myeloma; Penicillin Resistance; Sulbenicillin; Tetracyclines

Topics: Bacterial Infections; Child; Humans; Minocycline; Tetracyclines

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Clindamycin; Drug Combinations; Gentamicins; Humans; Microbial Sensitivity Tests; Minocycline; Nafcillin; Otorhinolaryngologic Diseases; Sulfamethoxazole; Surgical Procedures, Operative; Ticarcillin; Tobramycin; Trimethoprim

In the course of treating twenty patients with acute urinary tract infections, the toxicity and efficacy of a small dosage regimen (50 mg p.o., t.i.d.) of minocycline were evaluated. No vestibular symptoms attributable to minocycline treatment were observed in any of the cases entered in this study. Adverse reactions included mild nausea in 1 case and urticaria in another case. Minocycline with this dosage regimen sterilized the urine of 90% of patients with acute urinary tract infections.

Topics: Adult; Aged; Bacterial Infections; Bacteriuria; Cystitis; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Minocycline; Pyuria; Tetracyclines; Urinary Tract Infections

Topics: Animals; Bacterial Infections; Guinea Pigs; Legionnaires' Disease; Minocycline; Pneumonia; Tetracyclines

Topics: Adult; Aged; Bacterial Infections; Diarrhea; Erythromycin; Female; Fever; Headache; Humans; Legionnaires' Disease; Male; Middle Aged; Minocycline; United States

Trimethoprim-sulfamethoxazole, 2 tablets twice daily for 90 days, or minocycline-hydrochloride, 100 mg. twice daily for 14 days, was given to 15 and 14 men, respectively, with culture-proved bacterial prostatitis. Given as prescribed both agents seemed equally effective in controlling symptomatic recurrence during the 12 months after cessation of therapy.

Topics: Bacterial Infections; Drug Combinations; Humans; Male; Minocycline; Prostatitis; Recurrence; Sulfamethoxazole; Tetracyclines; Trimethoprim

Topics: Adult; Aged; Bacterial Infections; Cochlea; Female; Humans; Male; Middle Aged; Minocycline; Otorhinolaryngologic Diseases; Tetracyclines; Vestibule, Labyrinth

24 patients with severe infections were treated with intravenous minocycline 100 mg every 12 hours. Average blood levels were within therapeutic ranges during the first 12 hours after the initial dose. Determination of efficacy of therapy in 23 of the patients who were evaluable showed that clinical and bacteriological results were satisfactory in 20 patients, unsatisfactory in 2, and questionable in 1. One patient developed a fatal secondary infection which may have been related to prior therapy with minocycline. No toxicities or side-effects were observed.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cellulitis; Humans; Injections, Intravenous; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracyclines; Urinary Tract Infections

Topics: Adolescent; Adult; Aged; Bacterial Infections; Drug Evaluation; Female; Humans; Male; Middle Aged; Minocycline; Tetracyclines

Minocycline was the most active of six antibiotics tested against 65 clinical isolates of Acinetobacter calcoaceticus (syn.: Herellea, Mima) received from six medical centers. In the Bauer-Kirby disk susceptibility test, all isolates were rated susceptible to minocycline, gentamicin, and polymyxin; 25% were resistant to tetracycline. In agar dilution tests, minocycline was two to four times more potent than gentamicin or polymyxin and eight times more potent than tetracycline. Ampicillin and cephalexin were relatively ineffective. Against lethal infections produced by five strains of A. calcoaceticus in mice, minocycline was, in general, more active than gentamicin or polymyxin on a dosage basis and significantly more active on a blood-level basis. Minocycline was significantly more potent than tetracycline on both dosage and blood-level bases against tetracycline-sensitive and -resistant strains. In the last decade there has been an increase in the reported incidence of acinetobacters in a variety of infections. The cultures are susceptible to few antibiotics. Our data show that minocycline could offer an effective alternative to the more toxic drugs for the treatment of these infections. Susceptibility should be determined with minocycline disks.

Topics: Acinetobacter; Ampicillin; Animals; Anti-Bacterial Agents; Bacterial Infections; Cephalexin; Female; Gentamicins; Mice; Minocycline; Polymyxins; Tetracycline; Tetracyclines

Topics: Adult; Aged; Bacterial Infections; Female; Humans; Injections, Intravenous; Male; Middle Aged; Minocycline; Postoperative Complications; Tetracyclines

Topics: Acute Disease; Antibiotics, Antitubercular; Bacterial Infections; Cephalexin; Chronic Disease; Clindamycin; Drug Combinations; Erythromycin; Gentamicins; Humans; Methods; Minocycline; Otorhinolaryngologic Diseases; Penicillins; Streptomycin; Tobramycin

The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of Klebsiella, Enterobacter, and Pseudomonas aeruginosa in concentrations of 0.4 to 3.1 mug/ml and all strains of Escherichia coli and Proteus mirabilis in concentrations of 0.8 to 12.5 mug/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 mug or less/ml, it did act synergistically with gentamicin against 43% of the Enterobacteriaceae tested in clinically achievable concentrations; significant synergy was most common with E. coli (60%). Minocycline inhibited 62% of Bacteroides fragilis, 71% of Clostridium, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 mug or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 mug or less/ml, it did act synergistically with minocycline against 20% of B. fragilis, 67% of Clostridium, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of E. coli, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.

Topics: Abdomen; Bacteria; Bacterial Infections; Drug Synergism; Gentamicins; Minocycline; Tetracyclines

A new tetracycline (minocycline) and ampicillin were compared in the treatment of 217 adults with common infections seen in general practice. Minocycline had an overall clinical effectiveness comparable with ampicillin, though minocycline was more frequently prescribed for suspected staphylococcal infections with satisfactory results in 25 (26). Minocycline was significantly more effective in vitro against common pathogenic organisms than ampicillin. All strains of staphyloccocci isolated were sensitive to minocycline while 15 (27) were resistant to ampicillin. Minocycline and ampicillin were no different in the occurrence of mild side effects. Dizziness was troublesome for 23 (127) patients on minocycline and resulted in four patients discontinuing treatment.

Topics: Adult; Ampicillin; Bacterial Infections; Family Practice; Female; Humans; Male; Minocycline; Penicillin Resistance; Tetracyclines

Selected antibiotic advertisements in medical journals are discussed to illustrate the misleading information that is often disseminated to physicians by the pharmaceutical industry. Laboratory and clinical data are presented to question the validity of selected advertisements which (1) encourage the use of Keflex for severe respiratory infections in children, (2) recommend the use of Keflex for the treatment of bacterial bronchitis, (3) suggest that high tissue penetration is a unique property of Vibramycin, (4) present pooled susceptability data which do not reflect microbial resistance patterns in the patient's hospital, (5) recommend twice-daily administration of Ancef for urinary tract infections but do not clearly state the potential danger of this regimen for other infections, (6) suggest that gentamicin should be given to adults in only two dosage sizes for the treatment of serious Gram-negative infections, and (7) lead the reader to assume that only women need to be treated for Trichomonas infections. It is suggested that as antibiotics are marketed, hospital therapeutics committees should evaluate their advantages and permit formulary additions for only those agents demonstrating increased efficacy, decreased toxicity or decreased cost. Pharmacists who monitor drug therapy can provide information to the physician which will increase his awareness of optimal antibiotic therapy.

Topics: Advertising; Anti-Bacterial Agents; Bacterial Infections; Bronchitis; Cefazolin; Cephalexin; Doxycycline; Gentamicins; Haemophilus Infections; Haemophilus influenzae; Minocycline; United States; United States Food and Drug Administration

Several antibiotics were evaluated in model infections produced in mice with each of two strains of Fusobacterium necrophorum. In one model, local abscesses occurred at the site of subcutaneous injection; in another intra-abdominal abscesses were produced when the organisms were injected into the peritoneal cavity. Treatment with effective antibiotics prevented the formation of abscesses or minimized the size of the lesions. Several treatment schedules were used. Minocycline was the most active antibiotic of the seven agents tested against both strains and in both models. Clindamycin was equal to minocycline against one strain with certain multiple dose treatment schedules and less active with others. Protective effects in mice were achieved with serum levels of minocycline and clindamycin that appear to be clinically achievable. Doxycycline was less active than minocycline, and tetracycline was relatively ineffective, as were cephalexin, ampicillin and penicillin G.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Female; Fusobacterium; Mice; Minocycline; Tetracyclines

Topics: Adult; Age Factors; Amoxicillin; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbenicillin; Cefazolin; Cephacetrile; Cephalexin; Cephalosporins; Cephradine; Child; Child, Preschool; Cyclacillin; Doxycycline; Floxacillin; Humans; Infant; Infant, Newborn; Minocycline; Penicillin G; Pivampicillin; Tetracyclines; Trimethoprim

Topics: Bacterial Infections; Child; Child, Preschool; Cystic Fibrosis; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Tetracyclines

Topics: Bacteria; Bacterial Infections; Doxycycline; Humans; Leukemia; Minocycline; Neoplasms; Tetracycline

Topics: Acute Disease; Aged; Bacterial Infections; Bronchitis; Bronchopneumonia; Female; Humans; Lung Diseases; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Tetracycline

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

Topics: Bacteria; Bacterial Infections; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Tetracycline

Topics: Bacteria; Bacterial Infections; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Staphylococcus; Streptococcus; Streptococcus pneumoniae; Tetracycline