minocycline and Pneumonia--Ventilator-Associated

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Sulbactam; Tigecycline; Treatment Outcome

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

In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; 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

The present study examined the effect of high-dose cefoperazone-sulbactam combined with tigecycline against ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumannii(XDR-AB).. 42 patients with VAP due to XDR-AB infection were randomized into two groups: the TIG group (received tigecycline injection) and the TIG+CFS group (received tigecycline and cefoperazone-sulbactam (1 : 1) injection). Pulsed field gel electrophoresis (PFGE) was used for genotyping the isolated XDR-AB. The microdilution method was used to test the minimum inhibitory concentration (MIC) of cefoperazone-sulbactam or tigecycline in vitro and the combined effect was determined with the checkerboard method.. The total combined effectiveness rate (including all patients who demonstrated an improved condition) was significantly higher in the TIG+CFS group (85.7%) compared with the TIG group (47.6%) (p = 0.010). No significant differences were noted with regard to the adverse reactions between the two groups. The 42 isolated XDR-AB strains were classified into four types. The MIC of the two drugs in combination was significantly lower than that of each drug used alone (p < 0.05).. High dose of cefoperazone-sulbactam can improve the antimicrobial activity of tigecycline against XDR-AB.
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Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cefoperazone; Cohort Studies; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Prospective Studies; Sulbactam; Tigecycline; Treatment Outcome

In 12 of 13 phase 3 and 4 comparative clinical trials, all-cause mortality was higher in the tigecycline group versus the comparator group. Study-level mortality risk differences were pooled using a random-effects meta-analysis. Statistical models evaluated the association between patient-level all-cause mortality and baseline factors using logistic regression, recursive partitioning [classification and regression tree (CART) analysis] and survival techniques. The estimated risk difference (tigecycline minus comparator) in all-cause mortality from the meta-analysis was 0.6% (95% confidence interval 0.1-1.2%). Statistical modelling identified baseline bacteraemia associated with mortality only in the tigecycline group. In patients with ventilator-associated pneumonia (VAP) and baseline bacteraemia, mortality was 50.0% (9/18) for tigecycline versus 7.7% (1/13) for the comparator group. Study-level and patient-level analyses have identified that patients in the hospital-acquired pneumonia trial, particularly those with VAP with baseline bacteraemia, were at a higher risk of clinical failure and mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Survival Analysis; Tigecycline; Treatment Outcome

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

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

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

The aim of the study was to evaluate the clinical success rate of 73 patients with ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR)-Acinetobacter spp. treated with tigecycline in seven intensive Care Units in Argentina and to determine which predictor variables were significant in this context. Clinical success in our patients was 69.86% (Ci= 58.65-81.07%) 51/73, without significant differences between patients with VAP due to MDR-Acinetobacter spp. carbapenem-susceptible or carbapenem-resistant and only susceptible to colistin, minocyline and tigecycline (70% 44/73 vs. 69% 29/73 respectively, p=0.9006), and between patients who received <48h of prior antibiotics (including those who did not receive any) and those who received >48h of prior antibiotics (73.3% 22/30 vs 67.4% 29/43 respectively, p=0.7791). Age >67 and using other method than BAL for respiratory sampling were identified as predicting variables for negative clinical outcome. Our results suggest that tigecycline may be an acceptable alternative for therapy in patients with VAP caused by MDR-Acinetobacter spp. Nevertheless, only controlled clinical trials will provide the evidence to support approval for new indications.

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchoalveolar Lavage; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

The off-label uses of tigecycline (TGC) to treat ventilator-associated pneumonia (VAP) have aroused worldwide concerns. The efficacy about TGC has been recently reported. However, the adverse events (AEs) remain controversial. Our study aims to analyze the safety of the high-dose (HD) regimens in the treatment of VAP due to multidrug-resistant (MDR) pathogens.The clinical data of 134 patients who were diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care Unit (NCU) were analyzed retrospectively. The incidence and the occurrence time of AEs, 28-day mortality, and the factors of clinical effectiveness were explored.A total of 54 patients received the standard dose group (SD), 69 in the HD, and 11 in the nonstandard HD group (NHD). Acinetobacter baumannii were the main pathogenic bacteria. There was no statistic difference in the incidence of AEs and the 28-day mortality among the 3 groups (P > .05). Total bilirubin (TBIL) increased significantly after SD of TGC treatment (P = .004). Liver dysfunction occurred the latest (10.83 ± 7.08), not in the duration of HD group (9.63 ± 3.92), whereas in the SD group (13.00 ± 7.57) and NHD group (12.64 ± 3.70). Patients with septic shock, MODS, and higher APACHE II score were of high risk in mortality. The HD group was associated with higher clinical effective rate and bacteria clearance rate.HD TGC was relatively safe and tolerable in ICU patients. The risk of side effects was related to the TGC duration, although not increased as the dosage rose. Full course of the HD regimen was associated with better outcomes for the treatment of VAP patients, especially for the MDR gram-negative bacilli infection. Inappropriate antimicrobial treatment might lead to clinical treatment failure.

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome; Young Adult

To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy.. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients.. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality.. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Salvage Therapy; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

To evaluate the efficacy of tigecycline for treatment of ventilator-associated pneumonia in critically ill elderly patients.. Data of critically ill elderly patients with ventilator-associated pneumonia treated with tigecycline in the intensive care unit was collected from June 2011 to March 2014 in this retrospective study, to evaluated the clinical efficacy of tigecycline.. A total of 79 patients (83.5% male) were included, the mean age was 84 years old (rang, 65 years to 100 years old). Acinetobacter baumannii (39.1%), Pseudomonas aeruginosa (35.0%) and Klebsiella pneumonia (23.8%) were the most common pathogens.All patients were treated with tigecycline, 54.4% combined with other antimicrobial agents, 35.4% treated with double dose of tigecycline, and the mean course of antibiotic treatment was 9 days (range, 2 days to 22 days). After treatment, clinical success were recorded in 44 patients (55.7%), clinical failure were recorded in 29 patients, clinical uncertainty were recorded in 6 patients.28 days after treatment, patients' overall mortality was 39.0%.The clinical success rates were associated with acute physiology and chronic health evaluation (APACHE) Ⅱ score less than 15 (the clinical success rates were 72.2% and 41.9% in patients with APACHE Ⅱ score<15 and APACHE Ⅱ score≥15, respectively; P=0.007); treated with double dose of tigecycline (71.4% vs 47.1%, P=0.037) or combination regimens were also had significant difference (67.4% vs 41.7%, P=0.022).. Treatment of tigecycline combined with other antimicrobial agents and double dose of tigecycline may both can improve clinical efficacy in critically ill elderly patients with ventilator-associated pneumonia.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; APACHE; Critical Illness; Female; Humans; Intensive Care Units; Male; Minocycline; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Tigecycline

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: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Minocycline; Pneumonia, Ventilator-Associated; Prognosis; Retrospective Studies; Salvage Therapy; Survival Analysis; Tigecycline; Tunisia

This study investigated the minimum inhibitory concentration (MIC) values and in vitro activity of colistin in combination with tigecycline against carbapenem-resistant Acinetobacter baumannii strains isolated from patients with ventilator-associated pneumonia (VAP) using the E-test method.. A total of 40 A. baumannii strains, identified using the Phoenix Automated Microbiology System (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) by conventional methods, were included in this study. Pulsed-field gel electrophoresis was performed to examine the clonal relationships between isolates. The carbapenem resistance of the strains to colistin and tigecycline was assessed using the E-test method (Liofilchem, Roseto Degli Abruzzi, Italy). The in vitro activity of colistin in combination with tigecycline was evaluated using the fractional inhibitor concentration (FIC) index.. While only 1 of 40 A. baumannii strains was determined to be colistin resistant, 6 were tigecycline resistant. The MIC50, MIC90, and MIC intervals of the A. baumannii strains were 0.19, 1.5, and 0.064‒4 μg/ml for colistin and 1, 8, and 0.094‒256 μg/ml for tigecycline, respectively. No synergistic effect was observed using the FIC index; 8 strains exhibited an indifferent effect and 32 exhibited an antagonist effect. Three of the six strains that were resistant to tigecycline were indifferent; the remaining three were antagonistic. The colistin-resistant strain also exhibited an antagonist effect.. In contrast to their synergistic effect against carbapenem-resistant A. baumannii isolates, colistin and tigecycline were highly antagonistic to carbapenem-resistant A. baumannii strains isolated from patients with VAP when the drugs were administered together. Therefore, alternative treatment options should be used during the treatment of VAP attributed to A. baumannii.

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Young Adult

Tigecycline is an antibiotic with a broad spectrum of activity. Similar to tetracycline antibiotics, tigecycline exerts bacteriostatic activity. Earlier studies documented the safety and efficacy of tigecycline for complicated intra-abdominal and complicated skin and skin-structure infections, which led to its approval. Recent systematic reviews and meta-analyses have suggested increased risk of death in patients receiving tigecycline compared to other antibiotics. The Food and Drug Administration has warned clinicians about increased risk for death in patients who received tigecycline with certain severe infections and have issued a black box warning. The increased mortality risk with tigecycline is most apparent in patients treated for hospital-acquired pneumonia, particularly ventilator-associated pneumonia. The cause of excess deaths in these trials is uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection. Further experience with tigecycline for serious infections with drug-resistant pathogens is currently warranted.

Topics: Anti-Bacterial Agents; Communicable Diseases; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Minocycline; Pneumonia, Ventilator-Associated; Risk Assessment; Tigecycline; United States; United States Food and Drug Administration

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Tigecycline; Treatment Outcome; Young Adult

To analyze the clinical features of pandrug-resistant Acinetobacter baumannii (PDR-Ab) in the Chinese PLA General Hospital and compare the efficacies of different antibiotic treatments in aged patients with ventilator-associative pneumonia (VAP) caused by PDR-Ab.. Data were collected from all isolated PDR-Ab strains in our hospital from April 2009 to April 2010. The clinical features, treatment, and outcomes were retrospectively reviewed.. PDR-Ab was found to be the dominant pathogen in 42 of 126 aged VAP patients. Cefoperazone/sulbactam plus minocycline showed good efficacy in 20 patients with PDR-Ab VAP, showing a clinical cure rate of 65% (13/20) and a bacterial eradication rate of 40% (8/20). Another 22 patients were treated with other antimicrobial drugs, achieving a clinical cure rate of 22.7% (5/22) and a bacterial eradication rate of 13.6% (3/22). The factors influencing bacterial clearance were prolonged length of hospital stay and mechanical ventilation prior to positive culture (all P<0.01).. Cefoperazone/sulbactam plus minocycline can be an effective treatment for VAP caused by PDR-Ab.

Topics: Acinetobacter baumannii; Aged, 80 and over; Anti-Bacterial Agents; Cefoperazone; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Treatment Outcome

Topics: Anti-Bacterial Agents; Extracorporeal Membrane Oxygenation; Humans; Infusions, Intravenous; Minocycline; Plasma; Pneumonia, Staphylococcal; Pneumonia, Ventilator-Associated; Respiratory Insufficiency; Tigecycline; Young Adult

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

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

Topics: Acinetobacter; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic; Tigecycline; Treatment Outcome

Tigecycline was approved for the treatment of complicated intra-abdominal and complicated skin/skin structure infections. Because of its in vitro effectiveness for multidrug-resistant (MDR) isolates, tigecycline has been prescribed more broadly. This study evaluated tigecycline use after its first introduction in Taiwan and experience with tigecycline for the treatment of MDR Acinetobacter baumannii (MDRAB) infection, especially for ventilator-associated pneumonia.. Patients treated with tigecycline were collected retrospectively from February 2008 to July 2008 in Taipei Veterans General Hospital, a 2,900-bed tertiary care medical center in Taiwan. Patients were divided into three groups according to the indications: Group 1, Food and Drug Administration-approved indications; Group 2, health care-associated pneumonia (HAP); and Group 3, urinary tract infection, osteomyelitis, bacteremia, etc. Cases of MDRAB were also identified.. Among 66 cases, indications for the administration of tigecycline included Food and Drug Administration-approved indications (12, 18.2%), HAP (38, 57.6%), bacteremia (3, 4.5%), catheter-related infections (3, 4.5%), urinary tract infection (4, 6.1%), osteomyelitis (4, 6.1%), and others (2, 3%). Clinical outcome was positive in 20 cases, with higher clinical success rate for Group 1 than Group 2, which may correlate with higher Sequential Organ Failure Assessment score, older age, and more frequent intensive care admission in Group 2. Of the microbiologically evaluable cases, MDRAB predominated (33/51, 64.7%). Among infections with MDRAB (excluding pneumonia without ventilator), the clinical success rate was 12% (3/25).. The most common indication for the prescription of tigecycline was HAP. Success rate for MDRAB infection was lower than that previously reported, possibly because of serious underlying conditions and comorbidities in our patients. Because of limited choices, physicians should weigh the risk and benefit for prescribing tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Humans; Middle Aged; Minocycline; Off-Label Use; Pneumonia, Ventilator-Associated; Retrospective Studies; Taiwan; Tigecycline; Treatment Outcome

The aim of this study was to evaluate the clinical success rate of the patients with ventilator-associated pneumonia (VAP) treated with tigecycline.. Data from patients with established criteria of VAP were collected using a web-based reporting system from 16 February, 2006 to June 23, 2009. One hundred and seventeen patients coming from 10 ICUs from Argentina were studied.. Overall, attending physician reported clinical success in 74 patients (63%; 95%CI 54.08-72.41%). Global mortality proportion was 33% (39/117 patients). Patients with APACHE II score at admission > or = 15 showed a clinical success rate significantly lower and a mortality rate significantly higher than those with APACHE II score at admission less than 15 (52.6% [30/57] vs 73.3% [44/60]; p 0.0332, and 45.6% [26/57]vs 21.7% [13/60]; p 0.0108). The etiology of VAP was established in 60 patients (51%). Acinetobacter spp. (59%; in 84% of cases carbapenems-resistant), and methicillin-resistant Staphylococcus aureus (22%) were the most common microorganisms isolated. Eleven patients (1.5%) had VAP with bacteremia (respiratory sample and blood cultures positive for the same pathogens).. As initial evidence, our results suggest that tigecycline may be an acceptable alternative for therapy in patients with VAP. Nevertheless, only controlled clinical trials will provide the evidence to support approval for new indications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Utilization; Female; Hospital Mortality; Hospital Records; Humans; Intensive Care Units; Latin America; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Prospective Studies; Registries; Tigecycline; Treatment Outcome; Young Adult

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

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

Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most important pathogens in intensive care units related to morbidity and mortality, especially in ventilator-associated pneumonia (VAP). In this study, 80.5% of isolates were MDR. The antimicrobial susceptibilities for 12 different antibiotics of MDR A. baumannii isolated from VAP were tested. Among the MDR A. baumannii isolates, resistance rates were found to be 95.5%, 72.7%, 80.3%, 71.2% and 68.2% for ciprofloxacin, cefepime, imipenem, meropenem and cefoperazone/sulbactam, respectively. Netilmicin resistance was detected in 30.3% of the isolates. Resistance rates for colistin and tigecycline were 0% and 25.8%, respectively. It is obvious that new alternative drugs are needed for the treatment of MDR A. baumannii-related VAP owing to high resistance to carbapenems, quinolones, aminoglycosides and cefoperazone/sulbactam. Although colistin appears to be a good choice, adverse reactions and unavailability of colistin limit its wide usage in Turkey. Tigecycline, which will shortly be introduced commercially in Turkey, is very effective against MDR A. baumannii isolates and shows promising results to solve the problem, however resistance rates should be monitored closely.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Turkey

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

To evaluate early experience with tigecycline alone or in combination with other antimicrobials for treatment of ventilator-associated pneumonia (VAP) and/or bacteremia caused by multidrug-resistant Acinetobacter baumannii.. Retrospective case series.. University-affiliated medical center.. Twenty-five patients with multidrug-resistant A. baumannii who received tigecycline for VAP (19 patients), bacteremia (3), or VAP plus bacteremia (3) between September 1, 2005, and May 31, 2006. Five patients were treated with tigecycline alone.. Primary outcomes were resolution of clinical signs and symptoms of the infection and documented microbial eradication of A. baumannii with tigecycline. Overall, 21 (84%) of the 25 patients had clinical resolution. Four had clinical failure: three with VAP and one with VAP plus bacteremia that developed resistance to tigecycline during therapy. Microbial eradication was demonstrated in 12 (80%) of 15 patients in whom repeat cultures were obtained. Three patients with VAP had a recurrence of infection: one patient had two recurrences, and two patients had one recurrence each. All four recurrent episodes led to clinical resolution and microbial eradication. No patients discontinued tigecycline because of adverse events.. Tigecycline was effective in most of these 25 patients when used alone or in combination with other antimicrobials for VAP and/or bacteremia caused by multidrug-resistant A. baumannii. The emergence of a resistant strain while one patient was receiving therapy, however, is concerning.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline