minocycline and Pneumonia--Bacterial

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

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

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Critical Illness; Drug Therapy, Combination; Enterobacteriaceae; Humans; Minocycline; Pneumonia, Bacterial; Survival Analysis; Tigecycline; Urinary Tract Infections

Tigecycline is a novel antibiotic and it is the first glycylcycline of the tetracycline antibiotic class. It exhibits potent in vitro activity against causative pathogens that are most frequently isolated in patients with community-acquired pneumonia. The objective of this study is to review the literature about the efficacy of tigecycline in community-acquired pneumonia. Two randomized clinical studies showed tigecycline was not inferior when compared with levofloxacin for the treatment of patients with bacterial community-acquired pneumonia requiring hospitalization. Tigecycline was generally well tolerated in patients with community-acquired pneumonia. Major adverse effects were primarily gastrointestinal in nature. Tigecycline offers an antibiotic option that can be used in hospitalized patients with mild to moderate community-acquired pneumonia.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Minocycline; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

Tigecycline is a broad-spectrum antibiotic with activity against difficult-to-treat pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., Acinetobacter baumannii, and Gram-negative bacterial strains that produce extended-spectrum β-lactamases. Minimal organ toxicity and lack of dosage adjustment in most patients are important considerations for tigecycline use. Tigecycline has been shown to be as effective and safe as standard antimicrobial therapy for treatment of adults with complicated intra-abdominal infections, complicated skin and skin structure infections, and community-acquired bacterial pneumonia. The clearest applications of tigecycline are for on-label indications. Whether tigecycline should be utilized as therapy for other infections including hospital-acquired infections with a high likelihood of multidrug-resistant pathogens is a complex issue that requires ongoing assessment. This article offers an updated overview of tigecycline clinical studies, current microbial resistance patterns, pharmacokinetic/pharmacodynamic investigations, and safety analyses.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Tigecycline

Severe (life-threatening) meticillin-resistant Staphylococcus aureus (MRSA) infection continues to be treated with vancomycin despite accumulating evidence of poor outcome, increasing resistance and unachievable pharmacokinetic/pharmacodynamic (PK/PD) targets. The minimum inhibitory concentration (MIC) susceptibility breakpoint for vancomycin was recently reduced to 2 mg/L. Whilst the great majority of clinical isolates are thus still classified as susceptible, the available clinical evidence argues for a method-dependent breakpoint of 0.5 mg/L (broth dilution) or 1.0 mg/L (Etest), which would classify many strains as resistant, or at best intermediate. However, automated susceptibility testing systems are not currently capable of performing accurately at this low level, and such low breakpoints are unsatisfactory because the poor reproducibility of tests (plus or minus one doubling dilution) results in a critical non-reproducibility around the modal MIC of 1 mg/L described in most published data. Therefore, vancomycin should be used with caution in severe (life-threatening) staphylococcal disease and the MIC should always be reported by method. Daptomycin is generally preferred for bacteraemia/endocarditis and linezolid for pneumonia. Better outcome data for vancomycin, based on achievable PK/PD targets and using robust MIC tests, are urgently required.

Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Endocarditis, Bacterial; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Oxazolidinones; Pneumonia, Bacterial; Staphylococcal Infections; Teicoplanin; Tigecycline; Treatment Outcome; Vancomycin

Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data.

Topics: Achromobacter denitrificans; Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cystic Fibrosis; Doripenem; Humans; Minocycline; Pneumonia, Bacterial; Pseudomonas aeruginosa; Staphylococcus aureus; Stenotrophomonas maltophilia; Tigecycline

Cutaneous nocardiosis is an uncommon infectious disease that presents as a primary cutaneous infection or as a disseminated disease. It is often misdiagnosed because of its rarity and nonspecific clinical picture.. We report a case of each type. The first case is an immunocompetent patient who was infected by Nocardia while gardening and developed a superficial skin infection--one of the three clinical manifestations of primary cutaneous nocardiosis. The second case is an immunocompromised patient with pulmonary nocardiosis that extended to the skin as part of a disseminated disease.. The immunocompetent patient with primary cutaneous nocardiosis had the classical features of a superficial skin infection. He had a nodular–pustular lesion on the right arm, which appeared 7 days after gardening with bare hands. Nocardia was identified in a skin culture taken from a pustule, unfortunately not to the species level. Treatment with minocycline for 3 months resulted in full remission of the lesion. The immunocompromised patient with disseminated nocardiosis had high fever, productive cough, hemoptysis, and erythematous nodules and pustules on the extremities. N. brasiliensis was isolated from bronchial samples and skin. Treatment with a high dose of trimethoprim and sulfamethoxazole for five months resulted in full recovery from cutaneous and pulmonary complaints. No relapse of the infection was found on follow-up in either patient.. These cases demonstrate the need for a high degree of suspicion, focused clinical search, and appropriate laboratory procedures in the diagnosis and management of cutaneous nocardiosis.

Topics: Aged; Anti-Infective Agents; Diagnosis, Differential; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline; Nocardia; Nocardia Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Sulfamethoxazole; Trimethoprim

The available clinical experience with tigecycline is analyzed under the perspective of a systematic review of the literature, so in the already approved indications as in those off label indications reported in the recent literature. The safety profile is checked in the above mentioned clinical trials. The available information allows supporting tigecycline efficiency in the managing of complicated skin and soft tissues infections, complicated intrabdominales infections and community acquired pneumonias. Its usefulness is insinuated in addition in the managing infection by pathogen with high-level of resistance to antimicrobial. Nevertheless it is needed of major evidence in the matter and of a very sensible policy of use in the healthcare institution setting.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Gastrointestinal Diseases; Humans; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Pneumonia, along with influenza, is the leading cause of mortality associated with infectious diseases in the USA. Tigecycline is a novel antimicrobial agent that is active against a broad spectrum of pathogens. Our objective is to review the literature about the efficacy of tigecycline in community-acquired pneumonia (CAP). Data from various sources, including Pubmed, the European Medicines Agency (EMEA) and the US FDA were appraised. Tigecycline was found to be noninferior compared with levofloxacin for the treatment of patients with bacterial CAP requiring hospitalization. Recently, the drug was approved for the treatment of these patients by the FDA, but owing to some concerns, its application in the EMEA has been withdrawn. In addition, in a recent study concerns were expressed about the efficacy of tigecycline in the lungs using the current dosage. More data are needed about the pharmacokinetics of tigecycline in the lungs and its efficacy in severe CAP.

Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Guinea Pigs; Hospitalization; Humans; Lung; Minocycline; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

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

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

Tigecycline is a first-in-class glycylcycline, broad-spectrum, intravenous antibacterial developed to overcome the two major mechanisms of tetracycline resistance (ribosomal protection and efflux). The drug has been in use since 2005 for complicated intra-abdominal infections, and complicated skin and soft tissue structure infections, but is currently being assessed in the US for community-acquired pneumonia (CAP) in adults. In vitro, tigecycline had good activity against a range of Gram-positive, Gram-negative and atypical community-acquired respiratory tract pathogens implicated in CAP. Compared with other antibacterials, tigecycline has a prolonged post-antibiotic effect against key bacteria and a long serum elimination half-life in humans. The drug effectively penetrates lung tissue. The combined results of two well designed, phase III studies demonstrated that tigecycline 100 mg initially, followed by 50 mg every 12 hours for 7-14 days was not inferior to recommended dosages of levofloxacin in the treatment of hospitalized patients with CAP. Clinical cure rates were 89.7% versus 86.3% in the clinically evaluable population and 81.0% versus 79.7% in the clinical modified intent-to-treat population. Tigecycline was generally well tolerated in patients with CAP.

Topics: Anti-Bacterial Agents; Area Under Curve; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Half-Life; Humans; Injections, Intravenous; Minocycline; Pneumonia, Bacterial; Tigecycline

With its remarkable armamentarium of resistance and virulence factors, Staphylococcus aureus has emerged as a dominant pathogen causing pneumonia of all classifications. Rates of methicillin resistance are increasing as clinicians struggle to find ways to prevent the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and to effectively treat MRSA pneumonia. Community-associated MRSA has been identified as an important subset of MRSA with unique characteristics. Vancomycin remains a recommended first-line therapy for MRSA pneumonia, but resistance and therapeutic failures with vancomycin are being increasingly reported. Factors associated with vancomycin success or failure have been identified, including the genetics of the MRSA isolate, vancomycin lung penetration, minimum inhibitory concentration, and pharmacokinetic and pharmacodynamic variables. Retrospective analyses suggest that linezolid may provide improved outcomes compared with vancomycin for MRSA pneumonia, but validation in a prospective trial is currently lacking. Other treatment options are limited, but new prospects are being investigated. This paper reviews the epidemiology and pharmacotherapy of MRSA pneumonia.

Topics: Acetamides; Anti-Bacterial Agents; Anti-Infective Agents; Daptomycin; Humans; Linezolid; Methicillin Resistance; Minocycline; Oxazolidinones; Pneumonia, Bacterial; Staphylococcus aureus; Tigecycline; Vancomycin

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiratory Tract Infections; Treatment Outcome

Exposure-response analyses for efficacy and safety were performed for tigecycline-treated patients suffering from community-acquired pneumonia. Data were collected from two randomized, controlled clinical trials in which patients were administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A categorical endpoint, success or failure, 7 to 23 days after the end of therapy (test of cure) and a continuous endpoint, time to fever resolution, were evaluated for exposure-response analyses for efficacy. Nausea/vomiting, diarrhea, headache, and changes in blood urea nitrogen concentration (BUN) and total bilirubin were evaluated for exposure-response analyses for safety. For efficacy, ratios of the free-drug area under the concentration-time curve at 24 h to the MIC of the pathogen (fAUC(0-24):MIC) of ≥12.8 were associated with a faster time to fever resolution; patients with lower drug exposures had a slower time to fever resolution (P = 0.05). For safety, a multivariable logistic regression model demonstrated that a tigecycline AUC above a threshold of 6.87 mg · hr/liter (P = 0.004) and female sex were predictive of the occurrence of nausea and/or vomiting (P = 0.004). Although statistically significant, the linear relationship between tigecycline exposure and maximum change from baseline in total bilirubin is unlikely to be clinically significant.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bilirubin; Blood Urea Nitrogen; Community-Acquired Infections; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Regression Analysis; Sex Factors; Streptococcus pneumoniae; Tigecycline; Treatment Outcome; United States

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

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

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

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

Switch therapy is a management approach combining early discontinuation of intravenous (IV) antibiotics, switch to oral antibiotics, and early hospital discharge. This analysis compares switch therapy using tigecycline versus levofloxacin in hospitalized patients with community-acquired pneumonia (CAP).. A prospective, randomized, double-blind, Phase 3 clinical trial; patients were randomized to IV tigecycline (100 mg, then 50 mg q12h) or IV levofloxacin (500 mg q24h). Objective criteria were used to define time to switch therapy; patients were switched to oral levofloxacin after ≥6 IV doses if criteria met. Switch therapy outcomes were assessed within the clinically evaluable (CE) population.. In the CE population, 138 patients were treated with IV tigecycline and 156 were treated with IV levofloxacin. The proportion of the population that met switch therapy criteria was 67.4% (93/138) for tigecycline and 66.7% (104/156) for levofloxacin. The proportion that actually switched to oral therapy was 89.9% (124/138) for tigecycline and 87.8% (137/156) for levofloxacin. Median time to actual switch therapy was 5.0 days each for tigecycline and levofloxacin. Clinical cure rates for patients who switched were 96.8% for tigecycline and 95.6% for levofloxacin. Corresponding cure rates for those that met switch criteria were 95.7% for tigecycline and 92.3% for levofloxacin.. Switch therapy outcomes in hospitalized patients with CAP receiving initial IV therapy with tigecycline are comparable to those of patients receiving initial IV therapy with levofloxacin. These data support the use of IV tigecycline in hospitalized patients with CAP when the switch therapy approach is considered. CLINICALTRIALS.GOV IDENTIFIER: NCT00081575.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Female; Humans; Infusions, Intravenous; Levofloxacin; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Prospective Studies; Tigecycline; Treatment Outcome

Tigecycline exhibits potent in vitro activity against many community-acquired pneumonia (CAP) pathogens, including antibiotic-resistant ones. Its spectrum of activity and ability to penetrate lung tissue suggest it may be effective for hospitalized CAP patients. Hospitalized CAP patients (n=418) were randomized to receive intravenous (i.v.) tigecycline or levofloxacin. Patients could be switched to oral levofloxacin after receiving 6 or more doses of i.v. study medication. Therapy duration was 7 to 14 days. Coprimary efficacy end points were clinical responses in the clinically evaluable (CE: tigecycline, n=138; levofloxacin, n=156) and clinical modified intent-to-treat (c-mITT: tigecycline, n=191; levofloxacin, n=203) populations at test-of-cure (TOC). Safety was assessed in the mITT population (tigecycline, n=208; levofloxacin, n=210). Cure rates in tigecycline and levofloxacin groups were comparable in CE (90.6% versus 87.2%, respectively) and c-mITT (78% versus 77.8%, respectively) populations at TOC. Nausea and vomiting occurred in significantly more tigecycline-treated patients; elevated alanine aminotransferase and aspartate aminotransferase levels were reported in significantly more levofloxacin-treated patients. There were no significant differences in hospital length of stay, median duration of i.v. or oral antibiotic treatments, hospital readmissions, or number of patients switched to oral levofloxacin. Tigecycline was safe, effective, and noninferior to levofloxacin in hospitalized patients with CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Female; Haemophilus influenzae; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Moraxella catarrhalis; Multivariate Analysis; Ofloxacin; Pneumonia, Bacterial; Streptococcus pneumoniae; Tigecycline; Treatment Outcome

Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP.. In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy).. Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs.. These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.. NCT00081575.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infusions, Intravenous; Levofloxacin; Male; Middle Aged; Minocycline; Nausea; Ofloxacin; Pneumonia, Bacterial; Prospective Studies; Severity of Illness Index; Tigecycline; Treatment Outcome; Vomiting; Young Adult

Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Female; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Levofloxacin; Liver Function Tests; Male; Middle Aged; Minocycline; Ofloxacin; Pneumococcal Infections; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

Tigecycline (TGC), a first-in-class glycylcycline that has been approved for treating complicated skin and skin structure infections and complicated intra-abdominal infections, has an expanded spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, including resistant strains. The purpose of this study was to compare the efficacy and safety of TGC with levofloxacin (LEV) in adult hospitalised patients with community-acquired pneumonia (CAP) in a randomised, doubleblind, phase 3 multinational trial. This analysis evaluated TGC efficacy and safety in the European region. Hospitalised patients from 53 centres in 18 countries received 7-14 days of i.v. TGC (100-mg loading dose followed by 50 mg every 12 hours) or i.v. LEV (500 mg once or twice daily). Co-primary efficacy endpoints were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). Results indicated that 358 patients received at least 1 dose of study medication (mITT: TGC 177, LEV 181), 245 were CE (TGC 125, LEV 120). Demographics were similar in both groups and the majority of patients had a Fine Pneumonia Severity Index of II to IV (84.4% TGC, 78.2% LEV, mITT). At TOC (CE), TGC cured 112/125 patients (89.6%; 95% CI 82.9, 94.3) and LEV cured 103/120 patients (85.8%; 95% CI 78.3, 91.5), absolute difference of TGC-LEV 3.8% (95% CI -5.3, 12.8; test for noninferiority p<0.001). For those CE patients with a Fine score of

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Drug Therapy, Combination; Europe; Female; Humans; International Agencies; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Prospective Studies; Safety; Tigecycline; Treatment Outcome

We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit.. This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors.. For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline.. Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Fibrinogen; Gram-Negative Bacteria; Humans; Intensive Care Units; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

Our aim was to identify the pharmacokinetic/pharmacodynamic parameters of minocycline in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) and to identify the optimal clinical dose.. Minocycline MICs for 55 MAC clinical isolates from the Netherlands were determined. We also co-incubated primary isolated macrophages infected with MAC with minocycline. Next, we performed a 28 day HFS-MAC model dose-response study in which we mimicked pulmonary concentration-time profiles achieved in patients. The HFS-MAC model was sampled at intervals to determine the minocycline pharmacokinetics and MAC burden. We identified the AUC0-24/MIC ratios associated with 1.0 log10 cfu/mL kill below day 0 (stasis), defined as a bactericidal effect. We then performed 10000 Monte Carlo experiments to identify the optimal dose for a bactericidal effect in patients.. The MIC for 50% and 90% of cumulative clinical isolates was 8 and 64 mg/L, respectively. Minocycline decreased MAC bacterial burden below stasis in primary isolated macrophages. In the HFS-MAC model, minocycline achieved a microbial kill of 3.6 log10 cfu/mL below stasis. The AUC0-24/MIC exposure associated with a bactericidal effect was 59. Monte Carlo experiments identified a minocycline susceptibility MIC breakpoint of 16 mg/L. At this proposed breakpoint, the clinical dose of 200 mg/day achieved the bactericidal effect exposure target in ∼50% of patients, while 400 mg/day achieved this in 73.6% of patients, in Monte Carlo experiments.. Minocycline at a dose of 400 mg/day is expected to be bactericidal. We propose a clinical trial for validation.

Topics: Algorithms; Anti-Bacterial Agents; Bayes Theorem; Cell Line; Humans; Macrophages; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial

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

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

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

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

This study assessed the efficacy and safety of tigecycline in children with life-threatening infections.. We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre.. The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea.. Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Soft Tissue Infections; Tigecycline

The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established.. To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days.. The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical resolution rate was 66.7 % for both groups. The mortality rate during treatment was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The multivariate analysis showed that bilateral pneumonia was the only independent predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 % confidence interval, 1.015 to 7.272).. Patients treated with either tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but tigecycline group had a lower microbiological eradiation rate.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

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

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

Topics: Acute-Phase Reaction; Anti-Bacterial Agents; Biomarkers; Bronchoalveolar Lavage Fluid; Diagnostic Imaging; Humans; Immunoglobulin G; Male; Middle Aged; Minocycline; Orientia tsutsugamushi; Pneumonia, Bacterial; Scrub Typhus; Treatment Outcome

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies).

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Survival Analysis; Tigecycline; Treatment Failure

An increase in the antibiotic resistance among members of the Enterobacteriaceae family has been observed worldwide. Multidrug-resistant Gram-negative rods are increasingly reported. The treatment of infections caused by Escherichia coli and other Enterobacteriaceae has become an important clinical problem associated with reduced therapeutic possibilities. Antimicrobial carbapenems are considered the last line of defense against multidrug-resistant Gram-negative bacteria. Unfortunately, an increase of carbapenem resistance due to the production of Klebsiella pneumoniae carbapenemase (KPC) enzymes has been observed. In this study we describe the ability of E. coli to produce carbapenemase enzymes based on the results of the combination disc assay with boronic acid performed according to guidelines established by the European Community on Antimicrobial Susceptibility Testing (EUCAST) and the biochemical Carba NP test. Moreover, we evaluated the presence of genes responsible for the production of carbapenemases (bla KPC, bla VIM, bla IMP, bla OXA-48) and genes encoding other β-lactamases (bla SHV, bla TEM, bla CTX-M) among E. coli isolate. The tested isolate of E. coli that possessed the bla KPC-3 and bla TEM-34 genes was identified. The tested strain exhibited susceptibility to colistin (0.38 μg/mL) and tigecycline (1 μg/mL). This is the first detection of bla KPC-3 in an E. coli ST479 in Poland.

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Tigecycline

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

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

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

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

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

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

Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Vaccines; Body Weight; Bronchopneumonia; Disease Models, Animal; Female; Imipenem; Immunization; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Reproducibility of Results; Tigecycline; Time Factors

Human psittacosis caused by Chlamydophila psittaci is one of the most common zoonotic atypical pneumonias featuring pulmonary as well as extrapulmonary infections. Most of the cases involve avian contact history especially with psittacine birds. Herein we report a 44-year-old male patient displaying atypical pneumonia symptoms of intermittent fever, dry cough, chest pain, dyspnea, headache, hepatitis, and hyponatremia. He had two sick cockatiels, one of which had died a month previously. A microimmunofluorescence test was performed to check the serum antibody levels against Chlamydophila psittaci. The serum IgM titer showed positive titer of 1:256, 1:256, and 1:128 on Days 11, 23, and 43 after disease onset, respectively. His fever subsided soon and clinical symptoms improved after minocycline was administrated on Day 12. The psittacosis case was confirmed by history of psittacine bird contact, clinical symptoms, treatment response, and positive IgM titer. To our knowledge, this is the first report of a psittacosis case in Taiwan.

Topics: Adult; Animals; Anti-Bacterial Agents; Chlamydophila psittaci; Humans; Immunoglobulin M; Male; Minocycline; Pneumonia, Bacterial; Psittacosis; Taiwan; Zoonoses

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Drug Resistance, Bacterial; Female; Humans; Minocycline; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Humans; Minocycline; Pneumonia, Bacterial; Tigecycline

This study investigates the clinical and epidemiological features of Chryseobacterium indologenes infections and antimicrobial susceptibilities of C indologenes.. With 215 C indologenes isolates between January 1, 2004 and September 30, 2011, at a medical center, we analyzed the relationship between the prevalence of C indologenes infections and total prescription of colistin and tigecycline, clinical manifestation, antibiotic susceptibility, and outcomes.. Colistin and tigecycline were introduced into clinical use at this medical center since August 2006. The increasing numbers of patients with C indologenes pneumonia and bacteremia correlated to increased consumption of colistin (p = 0.018) or tigecycline (p = 0.049). Among patients with bacteremia and pneumonia, the in-hospital mortality rate was 63.6% and 35.2% (p = 0.015), respectively. Administration of appropriate antibiotics showed significant benefit in 14-day survival in patients with C indologenes bloodstream infection (p = 0.040). In bacteremic patients, old cardiovascular accident (p = 0.036) and cancer (p = 0.014) were the most common comorbidity. The most common co-infection pathogen in patients with C indologenes pneumonia was Acinetobacter baumannii (36/91, 39.6%), followed by Pseudomonas aeruginosa (23/91, 25.3%), carbapenem-resistant A baumannii (22/91, 24.2%), and Klebseilla pneumoniae (13/91, 14.3%). Antimicrobial susceptibility testing of the 215 isolates showed that trimethoprim-sulfamethoxazole was the most active agent (susceptibility rate: 87.4%), followed by cefoperazone-sulbactam (48.0%).. The present study showed a trend of increasing prevalence of C indologenes infection after introduction of colistin and tigecycline usage. The bacteremia group had higher mortality rate than the pneumonia group. Increasing resistance to piperacillin-tazobactam, ceftazidime, cefepime, and newer fluoroquinolone were noticed in our analysis. Trimethoprim-sulfamethoxazole was a potential antimicrobial agent in vitro for C indologenes. To avoid collateral damage, we emphasize the importance of antibiotic stewardship program.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Colistin; Drug Prescriptions; Drug Resistance, Bacterial; Female; Flavobacteriaceae Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Prevalence; Survival Analysis; Tigecycline

The efficacies of tigecycline and ceftazidime against fatal pneumonia in rats caused by an extended-spectrum β-lactamase (ESBL)-positive Klebsiella pneumoniae strain or its wild-type (WT) progenitor were compared. Ceftazidime at 12.5 or 50 mg/kg of body weight twice daily (b.i.d.) was effective (50% or 100% rat survival) in pneumonia caused by the WT isolate but unsuccessful (100% rat mortality) in pneumonia caused by the ESBL-positive variant. In contrast, tigecycline at 6.25, 12.5, or 25 mg/kg b.i.d. showed dosage-dependent efficacy up to 100% rat survival irrespective of the ESBL character of the infecting organism.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactamases; Ceftazidime; Dose-Response Relationship, Drug; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Rats; Survival Analysis; Tigecycline

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Lung; Minocycline; Pneumonia, Bacterial; Rats; Rats, Wistar; Tigecycline; Time Factors; Treatment Outcome

In 2007, 1.2 million people in the United States were hospitalized with pneumonia, and more than 52 000 died from the disease. Community-acquired bacterial pneumonia (CABP) can be caused by a variety of organisms as a result of patient factors such as comorbidities, epidemiologic conditions, or the setting in which the infection was contracted. Treatment of CABP differs depending on the types of bacteria that are suspected. In the last several years, due to the concern regarding multidrug-resistant organisms (MDROs), 2 new antibiotics have been developed and approved for use in CABP. Ceftaroline fosamil (Teflaro) was approved by the US Food and Drug Administration (FDA) in October 2010 and tigecycline (Tygacil) in March 2009. In clinical trials, both agents have been shown to be efficacious and are generally well tolerated. Although these agents have received approval as therapy for CABP, it is the responsibility of physicians and pharmacists to prudently use these antimicrobials where they are truly needed. Until these agents show superiority over conventional therapy for selected patient populations, given the wide variety of pharmacotherapy that can prove efficacious for pneumonia, the new agents should be reserved for patients who have known risk factors for MDROs. Further studies are warranted for these agents in the setting of CABP.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Community-Acquired Infections; Drug Approval; Humans; Minocycline; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Tigecycline; United States

Topics: Anti-Bacterial Agents; Bronchopneumonia; Cystic Fibrosis; Humans; Minocycline; Pneumonia, Bacterial; Tetracyclines; Tigecycline; Treatment Outcome

To investigate the clinical implication and prognostic predictors of tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii (MDRAB).. A retrospective observational study over a 32-month period for adult patients receiving tigecycline treatment at least 7 days for pneumonia involving MDRAB.. We reviewed 112 patients with 116 episodes of tigecycline-treated pneumonia involving MDRAB. The mean age was 70.8 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.7. Seventy episodes (60.3%) had clinical resolution. The episodes with monomicrobial MDRAB pneumonia had a significantly lower clinical resolution rate than polymicrobial pneumonia (14/31, 45.2% vs. 56/85, 65.9%; p = 0.044). The independent predictors for failure of clinical resolution were female gender, malignancy, bilateral pneumonia, monomicrobial pneumonia, and higher APHCHE II scores. Forty-two episodes (36.2%) had the 30-day mortality, and the only independent predictor was deterioration of pneumonia on chest radiographs.. A high disease severity, bilateral pneumonia, and monomicrobial MDRAB pneumonia predicted failure of clinical resolution, and deterioration of pneumonia predicted mortality. MDRAB in monomicrobial pneumonia was the most certain to be causal. The clinical resolution rate from such pneumonia might reflect the ultimate efficacy of tigecycline in treating MDRAB pneumonia and the overall efficacy might be overestimated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacteremia; Demography; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Prognosis; Retrospective Studies; Severity of Illness Index; Sex Factors; Tigecycline; Treatment Outcome

A male patient received non-chemotherapeutic drugs which induced deep neutropenia complicated with sepsis, bilateral pneumonia, acute respiratory insufficiency. Artificial pulmonary ventilation was applied. The examination of bronchoalveolar lavage showed the presence of the culture L. pneumophila (serogroup 1) in a concentration 2 x 10(3) CFU/ml. Antibacterial therapy with levofloxacin in a dose 1000 mg/day was conducted. In a week not only L.pneumophila but also Acinetobacter baumanii was isolated from bronchoalveolar lavage. Tigecyclin was added to levofloxacin treatment. Two air cavities were found in the left lung. The treatment reduced the size of these cavities, infiltrative changes in the lungs and respiratory insufficiency regressed. The patient was discharged from hospital This case is the first case in Russia of L.pneumophila isolation from bronchoalveolar lavage. The case is also characterized by use of tigecycline for treatment of combined legionella and akinetobacterial infection and cavities in the lungs in legionella pneumonia.

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Drug Therapy, Combination; Humans; Legionella pneumophila; Legionnaires' Disease; Levofloxacin; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

The aim of this study was to evaluate the efficacy of tigecycline in multidrug-resistant (MDR) Acinetobacter baumannii pneumonia. We retrospectively evaluated the outcome of adult patients with culture proven MDR A. baumannii pneumonia treated with tigecycline between January 2009 and March 2011. The study comprised a total of 72 MDR A. baumannii pneumonia cases (44 men, mean age 65.9±15.0). Tigecycline was used for a mean duration of 10.7±4.8 days. Microbiological eradication was observed in 47 cases (65.3%). Overall mortality was 55.5% and was lower in cases with microbiological eradication vs others (15/47 32% vs 25/25 100%, p<0.0001). Mortality and microbiological eradication rates were not different with monotherapy vs combination therapy (p>0.05). Patients who died had lower albumin levels, higher APACHE-II scores and CRP levels. The microbiological eradication rate of tigecycline in MDR A. baumannii was considerable. However, eradication of A. baumannii did not result in favorable clinical outcomes in those patients with low albumin, higher APACHE-II scores and CRP levels.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline

The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 microg/mL (imipenem-susceptible, IPM-S), and 8 and 2 microg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentration-time curve (AUC)/MIC(0-24 h) (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59 +/- 0.78, p = 0.006) and tigecycline (2.82 +/- 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21 +/- 0.52, p = 0.002) and tigecycline (3.21 +/- 0.28, p = 0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p = 0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p < 0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Area Under Curve; Disease Models, Animal; Female; Imipenem; Lung; Mice; Mice, Inbred C57BL; Minocycline; Pneumonia, Bacterial; Statistics, Nonparametric; Tigecycline

Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans; Imipenem; Immunosuppressive Agents; Lung Transplantation; Minocycline; Pneumonia, Bacterial; Radiography; Retrospective Studies; Tigecycline

The spread of antimicrobial resistance among members of the Enterobacteriaceae is a significant clinical threat. We report the treatment of pan-resistant Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a 49-year-old male and review available therapeutic options. Despite a poor prognosis, the patient recovered, but remains colonized with the pan-resistant isolate.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

We present a case of progressive Mycobacterium chelonae ssp. chelonae necrotizing pneumonia after hematopoietic stem cell transplantation (HSCT) in the presence of chronic graft-versus-host disease. The patient failed to respond to standard combination therapy with multiple agents and developed resistance to most drugs over the course of treatment. Tigecycline, a new glycylcycline antimicrobial agent with in vitro activity against M. chelonae, was then used with a clinical response to treatment. To our knowledge, this is the first reported case demonstrating tigecycline to have a degree of clinical effectiveness to treat refractory pulmonary infection with M. chelonae in an HSCT recipient.

Topics: Adult; Anti-Bacterial Agents; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Minocycline; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Pneumonia, Bacterial; Tigecycline; Transplantation, Autologous; Treatment Outcome

Topics: Anti-Bacterial Agents; Humans; Minocycline; Pneumonia, Bacterial; Tigecycline

Tigecycline is an extended-spectrum antibiotic with activity against Acinetobacter spp. (ACB), an increasingly common cause of nosocomial pneumonia. Although this compound is under investigation for this indication, supportive pharmacodynamic data are not yet available at this infection site. The objective of this study was to characterize the exposure-response relationship of tigecycline with ACB in an established murine pneumonia model.. The pharmacokinetic profile of tigecycline was evaluated in infected neutropenic mice. Tigecycline 6.25, 12.5, 25, 50, 100, 200, 300 and 400 mg/kg, in single or two to six divided subcutaneous doses, were tested against all ACB isolates. Efficacy, defined as the log(10) change in bacterial cfu/mL, was assessed after a 24 h course of therapy. Tigecycline exposures in serum were corrected for dose-specific protein binding. The relationship between the area under the free concentration-time curve to MIC (fAUC/MIC) and change in bacterial density was determined using the sigmoid E(max) model.. Tigecycline displayed linear pharmacokinetics with a mean half-life of 11.3 +/- 1.4 h. Efficacy correlated well with fAUC/MIC (R(2) = 0.96). The mean 80%, 50% effective and stasis exposures (fAUC/MIC) were 17, 8 and 6, respectively. Maximal efficacy for the five Acinetobacter baumannii studied was 3.4 log kill.. Tigecycline efficacy in this murine ACB pneumonia model was well predicted by fAUC/MIC. Requisite tigecycline exposures for efficacy appear to be higher for ACB pneumonia than for other pathogens reported of non-respiratory infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Female; Half-Life; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Serum; Tigecycline

Tigecyclin represents an important contribution for treatment of difficult-to-treat infections caused by polymicrobial or resistant flora. Its characteristics destinate it for use beyond the registered indications. Authors submit two case reports documenting its promising effect in patients with complicated pulmonary infection in whom standard treatment was not successful.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

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

Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections.. To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution.. A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients.. Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8).. In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.

Topics: Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bronchitis; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Urinary Tract Infections; Wound Infection

Elizabethkingia miricola is a Gram-negative rod that was initially isolated from condensation water of the space station Mir. This is the 1st reported case of human disease caused by this organism.

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lymphoma, Mantle-Cell; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis; Stem Cell Transplantation; Tigecycline

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

Topics: Actinobacteria; Aged; Anti-Bacterial Agents; Critical Illness; Female; Gram-Positive Bacterial Infections; Humans; Male; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tigecycline

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

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

A 53-year-old woman experienced a multidrug-resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 microg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100-mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 microg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 microg/ml. A follow-up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 microg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 microg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Kidney Transplantation; Liver Transplantation; Microbial Sensitivity Tests; Middle Aged; Minocycline; Osteomyelitis; Pneumonia, Bacterial; Spinal Diseases; Tetracycline Resistance; Tigecycline; Urinary Tract Infections

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

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

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

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

Topics: Adult; Chlamydia Infections; Chlamydophila pneumoniae; Humans; Male; Minocycline; Pneumonia, Bacterial; Severity of Illness Index; Treatment Outcome

A previously healthy 48-year-old man presented to his primary care physician with high fever, dry cough and dyspnea. Pneumonia was diagnosed and intravenous administration of imipenem/cilastatin was begun, but his respiratory condition worsened and he was admitted to our hospital with severe hypoxia. A chest radiograph showed reticular opacity and consolidation in both lung fields. The case was complicated with disseminated intravascular coagulation. Analysis of the bronchoalveolar lavage fluid showed increases in the total cell counts and an elevated percentage of lymphocytes. Sputum, blood and bronchoalveolar lavage examinations failed to reveal etiology to explain his severe respiratory illness. Treatment consisted of mechanical ventilation and administration of steroid pulse-therapy and gabexate mesilate. On the basis of his clinical course, we suspected possible atypical pneumonia, and began therapy with intravenous minocyclin and oral erythromycin administration. On the third hospital day, the arterial blood gas data improved and the bilateral pulmonary infiltration on the chest radiographs disappeared. Using paired sera, we detected increases of 1.35 in ID for anti-Chlamydia pneumoniae IgG antibodies by ELISA, and arrived at a diagnosis of Chlamydia pneumoniae pneumonia.

Topics: Acute Disease; Chlamydophila Infections; Chlamydophila pneumoniae; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Erythromycin; Gabexate; Humans; Male; Methylprednisolone; Minocycline; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Insufficiency; Treatment Outcome

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

We evaluated the in vitro activity of GAR-936, a novel glycylcycline antibiotic, against ten isolates of Chlamydia pneumoniae and five strains of C. trachomatis. Susceptibility testing was done in HEp-2 cells. The MIC90s and MBC90s of GAR-936, doxycycline, ofloxacin and clarithromycin against C. pneumoniae were 0.125, 0.25, 0.25 and 0.06 mg/l, respectively. The MICs and MBCs of GAR-936, doxycycline, ofloxacin and clarithromycin against C. trachomatis were 0.03-0.125, 0.25, 0.25-0.5 and 0.06 mg/l, respectively. GAR-936 had excellent activity against both chlamydial species and may have a potential role in the treatment of human chlamydial infection.

Topics: Adult; Anti-Bacterial Agents; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila Infections; Chlamydophila pneumoniae; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Tigecycline

Nocardiosis is a subacute or chronic suppurative infection caused by Nocardia species. Although it is more common in immunocompromised hosts, idiopathic pulmonary fibrosis (IPF) has not been recognized as a predisposing factor for nocardial infection. We report a case of IPF, in which pulmonary nocardiosis developed during treatment with prednisolone and cyclophosphamide. The risk of pulmonary nocardiosis may be increased in cases of IPF on immunosuppressive therapy. Since IPF often accompanies lung carcinoma, it is important to correctly differentiate nocardiosis from carcinoma.

Topics: Aged; Anti-Bacterial Agents; Causality; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Minocycline; Nocardia Infections; Pneumonia, Bacterial; Prednisolone; Pulmonary Fibrosis; Sputum; Tomography, X-Ray Computed

We report a case of pulmonary Nocardia (N.) otitidiscaviarum infection in a 76-year-old man with chronic respiratory infection. The patient responded poorly to intravenous imipenem and oral minocycline, but later improved after treatment with trimethoprim-sulfamethoxazole. Pulmonary infection with N. otitidiscaviarum should be considered in the differential diagnosis of chronic respiratory infections. Further studies are needed to evaluate the correlation between species and drug susceptibility.

Topics: Aged; Agricultural Workers' Diseases; Bronchoalveolar Lavage Fluid; Chronic Disease; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Imipenem; Male; Microbial Sensitivity Tests; Minocycline; Nocardia; Nocardia Infections; Opportunistic Infections; Pneumonia, Bacterial; Species Specificity; Trimethoprim, Sulfamethoxazole Drug Combination

Mycobacterium vaccae is a rapidly growing mycobacterial species that was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease, and three patients had cavitary lung disease. Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin.

Topics: Aged; Animals; Anti-Bacterial Agents; Cattle; Ciprofloxacin; Humans; Male; Middle Aged; Minocycline; Mycobacterium; Mycobacterium Infections; Neoplasms; Pneumonia, Bacterial; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Actinomycetales Infections; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Gentamicins; Humans; Immunocompromised Host; Lung Transplantation; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Rhodococcus equi; Teicoplanin