minocycline and Intraabdominal-Infections

Tigecycline has emerged as first line therapy for serious systemic infections due to important pathogens (except P. aeruginosa and Proteus sp.), including multi-drug resistant (MDR) and Gram negative bacilli (GNB), including carbapenem resistant Enterobacteriae. Tigecycline has a 'low resistance potential,' is protective against C. difficile, and is often the only antibiotic effective against MDR GNB, e.g., Klebsiella sp. Areas covered: Standard dose tigecycline therapy has been used for intra-abdominal infections, complicated skin/skin structure infections (cSSSIs), and CAP. Clinical experience with once daily high dose tigecycline (HDT), i.e., 200 - 400 mg (IV) x 1, then 100 - 200 mg (IV) q24 h, is reviewed. Optimal tigecycline efficacy is dependent on PK/PD based dosing. Suboptimal outcomes have been due to inappropriate use or suboptimal dosing. Expert commentary: Tigecycline's spectrum against nearly all important pathogens (including MSSA/MRSA, VSE/VRE, B. fragilis, C. difficile, MDR and GNB) assures tigecycline a critical place in the antibiotic armamentarium. Dosed optimally, HDT can be a cornerstone of antibiotic stewardship programs in preventing C. difficile, treating MDR GNB pathogens, and in preventing resistance. Properly used and optimally dosed, once daily HDT should be considered preferred therapy for severe systemic infections and those due to MDR GNB pathogens.

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

Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Drug Administration Schedule; Female; Humans; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; Tigecycline; Treatment Outcome

Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).. A total of 785 cIAI patients who received tigecycline were included (mean age 63.1 ± 14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9 ± 7.6 (n = 614) and 7.0 ± 4.2 (n = 108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n = 430) received tigecycline as monotherapy and 45.2% (n = 355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score >15 (250/330) and 54.2% (32/59) for patients with a SOFA score ≥ 7.. In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome; Young Adult

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

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

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

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

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

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

Tigecycline 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

As the spread of multidrug-resistant (MDR) and extensive drug-resistant (XDR) organisms constitutes a real threat for patients, new antimicrobials are needed. Tigecycline, the first-in-class glycylcycline, possesses an extended spectrum of antimicrobial activity including MDR and XDR organisms, which holds promise as a treatment option beyond currently approved indications and deserves expanded evaluation of its pharmacokinetics/pharmacodynamics (PK/PD).. This review highlights the areas where our knowledge on PK/PD of tigecycline has been both strengthened and questioned during the recent years. New information has become available on the PK of tigecycline in patients with complicated skin and skin structure infections, complicated intra-abdominal infection, community- and nosocomial-acquired pneumonia. Human PD data from clinical trials linking tigecycline drug exposure to clinical, microbiological and toxicological outcomes are also of great interest.. Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.

Topics: Anti-Infective Agents; Clinical Trials as Topic; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Glycylglycine; Humans; Intraabdominal Infections; Minocycline; Pneumonia; Tigecycline

This randomized, open-label, multi-center trial compared tigecycline (TGC), a broad-spectrum glycylcycline, with ceftriaxone-metronidazole (CTX/MET) for the treatment of complicated intra-abdominal infections (cIAI).. Eligible subjects were randomized to receive TGC 100 mg followed by 50 mg q 12 h or CTX 2 g qd plus MET 1-2 g daily for 4-14 days. Subjects were stratified by Acute Physiology and Chronic Health Evaluation (APACHE) II score ≤10 or >10 and could not receive oral therapy. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment 8-44 days after the last drug dose.. Clinical responses in the CE population were 81.8% (162/198) vs. 79.4% (150/189) for TGC and CTX/MET, respectively; a weighted estimate of the difference of 1.6 (95% confidence interval [CI] -6.4, 9.6). In the microbiologically evaluable (ME) population, microbiological eradication rates were 82.4% (98/119) for TGC vs. 79.6% (86/108) for CTX/MET: a difference of 2.7 (95% CI -7.9, 13.3). Common adverse events were nausea (21.6% TGC vs. 21.3% CTX/MET) and vomiting (17.7% TGC vs. 13.2% CTX/MET). Discontinuation rates because of adverse events were 7.8% for TGC and 6.4% for CTX/MET.. Tigecycline was effective in the treatment of cIAI and was non-inferior to CTX/MET for the treatment of cIAI in hospitalized adults. Clinical Trials Identifier: NCT00230971.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Drainage; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intraabdominal Infections; Male; Metronidazole; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum β-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Drug Therapy, Combination; Enterococcus; Escherichia coli; Female; Germany; Humans; Intensive Care Units; Intraabdominal Infections; Logistic Models; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Minocycline; Multiple Organ Failure; Prospective Studies; Sepsis; Severity of Illness Index; Skin Diseases, Bacterial; Staphylococcus aureus; Tigecycline; Treatment Outcome; Young Adult

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.. We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.. We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46).. TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carrier State; Clostridioides difficile; Clostridium Infections; Enterobacteriaceae Infections; Female; Humans; Incidence; Intraabdominal Infections; Male; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins; Tigecycline; Young Adult

Eravacycline, a novel fluorocycline antibiotic, has been evaluated against complicated mixed aerobic/anaerobic intra-abdominal infections but scant supporting in vitro data against anaerobes has been published. We found that eravacycline had good anaerobic in vitro activity with MICs of 4 μg/ml or less against all Bacteroides and Parabacteroides strains tested, except for two B. ovatus strains that had MICs of 8 μg/ml and one strain that had an MIC of 16 μg/ml. Eravacycline was four-to-eight fold more active than tigecycline.

Topics: Anti-Bacterial Agents; Bacteroides; Bacteroidetes; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Tetracyclines; Tigecycline

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

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

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

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

To study a cohort of patients with intra-abdominal postsurgical infection treated with tigecycline to analyze its effectiveness and mortality related factors.. Prospective study of patients with intra-abdominal postsurgical infection with microbiological isolation and treated with tigecycline.. Out of 103 patients only 61 full fit inclusion criteria. Mean age was 67 year-old and 72% were male. Charlson score was ≥ 3 in 65.5%, being diabetes and colon cancer the most prevalent diseases. Cancer surgery was the most frequent procedure (n=44, 72%) and previous antibiotic administration was present in 43 cases (69%). Pitt score was ≥ 3 in 69% and most prevalent bacteria were Escherichia coli (38 %), Enterococcus spp. (34%; mainly Enterococcus faecium) and Klebsiella pneumoniae together with Enterobacter cloacae (28%). Tigecycline was prescribed alone (17; 28%) or in combination with other antibiotics (44; 72%), mainly meropenem (25; 57%) or amikacin (19, 43%). 11 patients died (18%), all of which suffered extended cancer surgery and isolation of extended-spectrum betalactamase producing Enterobacteriaceae. Factors statistically associated to death in univariate analysis were Charlson score >3, pH <7.3 and leucocyte count >20.000 cells/mm3.. As being a cohort of patients treated with tigecycline, E. faecium isolation was very frequent. Non-fatal evolution was achieved in 82% cases, being tigecycline a potentially good option in the empiric treatment of very severe infections.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Postoperative Complications; Prospective Studies; Risk Factors; Spain; Tigecycline

The utility of tigecycline as compared with other antibiotic therapies in the treatment of patients with complicated intra-abdominal infection (cIAI) and the short- and long-term outcomes of a large cohort of severely ill patients were examined. We provide the first published data on post-discharge events for these patients.. Retrospective data for the cIAI cohort were obtained from a large clinical database. Patients aged ≥18 y were selected for inclusion based on hospitalization with a relevant diagnosis code and procedure code, and guideline-compliant antimicrobial therapy. Propensity scoring was used to reduce treatment-selection bias introduced by the use of observational data. Tigecycline patients were placed into quintiles based on propensity score and were matched 1:3.. The final model based on propensity score matching included 2,424 patients: Tigecycline (n = 606) and other antibiotic therapy (n = 1,818). Treatment was successful in 426 (70.3%) tigecycline-treated patients and in 1,294 (71.2%) patients receiving other antibiotics. Similar treatment success occurred across all infection sites. Among survivors, treatment failure was associated with a greater need for all-cause re-hospitalization at 30 d and 180 d. No differences in cIAI-related re-hospitalization and discharge status were observed.. Using propensity scores to match populations, similar outcomes were demonstrated between treatment with tigecycline and other antibiotics as expressed by treatment success, the need for re-admission, similar 30-d discharge status, and the need for re-admission at 180 d.

Topics: Anti-Bacterial Agents; Female; Humans; Intraabdominal Infections; Length of Stay; Male; Middle Aged; Minocycline; Patient Readmission; Propensity Score; Recurrence; Tigecycline; Treatment Outcome

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Colectomy; Enterocolitis, Pseudomembranous; Female; Humans; Intraabdominal Infections; Male; Metronidazole; Middle Aged; Minocycline; Recurrence; Retrospective Studies; Sepsis; Tigecycline; Treatment Outcome; Vancomycin

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

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

The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Blood Coagulation Tests; Female; Fibrinogen; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Partial Thromboplastin Time; Pneumonia; Prothrombin Time; Thrombin Time; Tigecycline; Young Adult

Based on tigecycline linear pharmacokinetic/pharmacodynamics, dose increases have been advocated to maximise activity especially when severe infections with high bacterial load and/or multidrug resistance are suspected. This practice-based observational study explored factors associated with tigecycline administration (100 mg/12h, 200 mg loading dose) in severely ill patients with complicated intra-abdominal infection (cIAI) admitted to four Surgical Critical Care Units (SCCUs).. Medical records of all consecutive adult patients with cIAI and controlled infection source requiring surgery and admission for ≥ 48 h to SCCU were reviewed and divided into patients treated with a regimen including tigecycline (tigecycline group) and those that not (control group). A logistic regression model was performed using "tigecycline administration" (dependent variable) and variables showing differences (p ≤ 0.1) in bivariate analyses (independent variables).. One hundred and twenty one patients were included. In the tigecycline group, higher percentage of patients (vs. controls) presented colon as surgical site (66.7% vs. 41.8%, p = 0.006), nosocomial infection (55.6% vs. 26.9%, p = 0.001), mechanical ventilation (48.1% vs. 28.4%, p = 0.025), chronic renal replacement therapy (40.7% vs. 19.4%, p =0.008), septic shock (72.2% vs. 46.3%, p = 0.004), and higher values of SAPS II (48.0 ± 15.0 vs. 39.6 ± 15.5, p = 0.003), SOFA at admission (7.0 ± 3.3 vs. 5.5 ± 3.7, p = 0.020), lactate-24h (2.5 ± 2.8 vs. 1.6 ± 0.9, p = 0.029) and CRP-72 h (207.4 ± 87.9 vs. 163.7 ± 76.8, p = 0.021). In the multivariate analysis (R2 = 0.187, p < 0.001) nosocomial infection (OR = 7.721; 95%CI = 2.193, 27.179; p = 0.001), colon as infection site (OR = 4.338; 95%CI = 1.432, 13.145; p = 0.009) and CRP-72 h (OR = 1.009 per-unit; 95%CI = 1.002, 1.016; p = 0.012) were associated with tigecycline administration.. In severely ill patients with cIAI, high-dose tigecycline administration was associated with nosocomial origin of cIAI and colon as source infection site.

Topics: Aged; Anti-Bacterial Agents; Critical Care; Critical Illness; Digestive System Surgical Procedures; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Peritonitis; Postoperative Complications; Prospective Studies; Retrospective Studies; Surgical Wound Infection; Tigecycline

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

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

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

Complicated skin and skin structure infections (cSSSIs) and intra-abdominal infections (IAIs) are problematic due to decreasing therapeutic options available against multidrug-resistant pathogens common among these types of infections. A total of 2245 isolates from African and the Middle Eastern (AfME) countries were collected to determine in vitro activity for tigecycline and comparators during 2007-2012 as part of the Tigecycline Evaluation Surveillance Trial program. Tigecycline was launched in the AfME in 2007 and remains active against a wide range of targeted pathogens worldwide. Isolates were recovered from cSSSI (1990) and IAI (255) from 38 sites in 11 AfME countries. Staphylococcus aureus was the most common species from cSSSI (27.9%), and the methicillin-resistant S. aureus rate was 25%. Enterococcus spp. (7.1%) and Streptococcus agalactiae (2.9%) were other common Gram-positive pathogens represented. Enterobacter spp. (14.5%), Pseudomonas aeruginosa (13.9%), Escherichia coli (11.4%), Klebsiella spp. (10.9%), and Acinetobacter spp. (7.2 %) were the most common Gram-negative species collected. Tigecycline MIC(90) values were 0.25 μg/mL against S. aureus. E. coli and Enterobacter spp. had tigecycline MIC(90) values of 1 and 2 μg/mL, respectively. E. coli was the most frequently collected species from IAI (28.3%), followed by Klebsiella spp. (20.8%), Enterococcus spp. (11.8%), and Stenotrophomonas maltophilia (6.3%). Isolates collected from IAI had the following tigecycline MIC(90) values: E. coli (1 μg/mL), Klebsiella spp. and other Enterobacteriaceae (2 μg/mL), Enterococcus spp. (0.25 μg/mL), and S. maltophilia (1 μg/mL). Tigecycline in vitro activity was observed against a broad spectrum of bacterial species, including strains resistant to other antimicrobial classes.

Topics: Africa; Anti-Bacterial Agents; Bacteria; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Middle East; Minocycline; Skin Diseases, Bacterial; Tigecycline

Topics: Anti-Bacterial Agents; Female; Humans; Intraabdominal Infections; Male; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

Tigecycline, a new glycylcycline antimicrobial agent, is indicated for the treatment of complicated skin structure infection (cSSTI), intra-abdominal infection (cIAI) and community acquired pneumonia. We aimed to evaluate the clinical and microbiological data together about tigecycline therapy.. Patients with cIAIs and cSSTIs were included in a prospective, observational follow-up. Patient follow-up forms were developed and clinical and microbiological data were recorded.. Of the 107 patients, 67 had cSSTIs, 40 had cIAIs. Tigecycline was used empirically in 37.5% of cIAIs and in 50.7% of cSSTIs. In 85.0% of the patients with cIAI and in 73.1% of the patients with cSSTI, clinical and/or microbiological response could be achieved. A drug change was made in 26.9% and 7.5% of the patients with cSSTI and cIAI respectively. Superinfection was detected in 14.9% of the cSSTI and 7.5% of the cIAI patients.. As a result, tigecycline can be safely used in the treatment of different infections. Compared with cSSTIs, the treatment response is better and the duration of treatment is shorter in cIAIs. However, MIC value must be determined at any rate if tigecycline is to be used in the treatment of Acinetobacter (MDR Acinetobacter, in particular) infections. Clinical cure and microbiological eradication rate of tigecycline therapy changes according to different clinical diagnosis and microorganism.

Topics: Anti-Bacterial Agents; Drug Substitution; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Superinfection; Tigecycline; Treatment Outcome

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

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

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

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

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Male; Microbial Sensitivity Tests; Minocycline; Omeprazole; Postoperative Complications; Tigecycline

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

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