colistin and Pneumonia--Ventilator-Associated

Nebulized colistin (NC) is a potential therapy for ventilator-associated pneumonia (VAP); however, the clinical efficacy and safety of NC remain unclear. This study investigated whether NC is an effective therapy for patients with VAP.. We performed a search in Web of Science, PubMed, Embase, and the Cochrane Library to retrieve randomized controlled trials (RCTs) and observational studies published at any time until February 6, 2023. The primary outcome was clinical response. Secondary outcomes included microbiological eradication, overall mortality, length of mechanical ventilation (MV), length of intensive care unit stay (ICU-LOS), nephrotoxicity, neurotoxicity, and bronchospasm.. Seven observational studies and three RCTs were included. Despite exhibiting a higher microbiological eradication rate (OR,2.21; 95%CI, 1.25-3.92) and the same nephrotoxicity risk (OR,0.86; 95%CI, 0.60-1.23), NC was not significantly different in clinical response (OR,1.39; 95%CI, 0.87-2.20), overall mortality (OR,0.74; 95%CI, 0.50-1.12), MV length (mean difference (MD),-2.5; 95%CI, -5.20-0.19), and the ICU-LOS (MD,-1.91; 95%CI, -6.66-2.84) than by the intravenous antibiotic. Besides, the risk of bronchospasm raised significantly (OR, 5.19; 95%CI, 1.05-25.52) among NC.. NC was associated with better microbiological outcomes but did not result in any remarkable changes in the prognosis of patients with VAP.

Topics: Anti-Bacterial Agents; Bronchial Spasm; Colistin; Humans; Pneumonia, Ventilator-Associated; Respiration, Artificial

Inhaled colistin is becoming increasingly popular against respiratory tract infections caused by multidrug resistant (MDR) Gram-negative bacteria because it may overcome the problems associated with intravenous (IV) administration.. To investigate the effectiveness and safety of inhaled colistin as monotherapy (without concomitant IV administration of colistin) in the treatment of respiratory tract infections caused by MDR or colistin-only susceptible Gram-negative bacteria.. PubMed and Scopus databases were searched. A systematic review and meta-analysis were conducted.. Twelve studies (373 patients receiving inhaled colistin for respiratory tract infection) were included. Ten studies evaluated patients with pneumonia (including 8 studies with ventilator-associated pneumonia) and 2 studies evaluated patients with ventilator-associated tracheobronchitis. Patients with infections due to MDR Acinetobacter baumannii and Pseudomonas aeruginosa were mainly studied. Daily dose of inhaled colistin and treatment duration varied in the individual studies. The pooled all-cause mortality was 33.8% (95% CI 24.6% - 43.6%), clinical success was 70.4% (58.5% - 81.1%) and eradication of Gram-negative bacteria was shown in 71.3% (57.6% - 83.2%) of cases.. Inhaled colistin monotherapy may deserve further consideration as a mode for colistin administration for the treatment of respiratory tract infections caused by MDR A. baumannii and P. aeruginosa.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

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

To evaluate whether intravenous plus inhaled combination (IV/INHCC) compared to intravenous monotherapy (IVCM) was associated with patient outcomes and identify factors influencing study outcomes.. PubMed and Scopus were searched till November 2016. Studies were included if they evaluated adult patients with lower respiratory tract infections due to MDR/XDR Gram-negative bacteria and reported comparative mortality data (adjusted and unadjusted) for patients receiving IV/INHCC versus IVCM. Random effects meta-analyses were performed.. Thirteen studies (11 retrospective, 2 prospective) were included. The overall quality of data was low to very low and characterized by the lack of adjusted data. The majority of the studies were designed to evaluate the outcome of the meta-analysis. Both IV and inhaled colistin were administered at variable doses. There was no difference in mortality between IV/INHCC and IVCM when all studies were combined (13 studies, 1115 patients, risk ratio 0.94, 95% confidence interval 0.81-1.08). Only the analysis that included studies with low-dose IV colistin showed significant difference in favor of IV/INHCC versus IVCM (0.65, 0.45-0.94).. Overall, low quality data suggest that IV/INHCC did not lower mortality in patients with MDR Gram negative infections unless low IV colistin dose was administered.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pneumonia, Ventilator-Associated; Prospective Studies; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome

In patients with ventilator-associated pneumonia, systemic use of antibiotics is the cornerstone of medical management. Supplemental use of aerosolized antibiotics with intravenous antibiotics in both experimental and clinical studies has been shown to have the following pharmacologic benefits: (1) aerosolized antibiotics reach the infected lung parenchyma without crossing the pulmonary alveolar capillary barrier; (2) aerosolized antibiotics increase anti-bacterial efficacy through increased local antibiotic concentration; and (3) aerosolized antibiotics decrease systemic toxicity. These benefits may be particularly beneficial to treat pneumonia caused by multidrug-resistant pathogens. Clinical data on the benefits of aerosolized antibiotics are more limited. Studies to date have not clearly shown improvements in time to extubation, mortality, or other patient-centered outcomes. At present, amikacin, colistin, and ceftazidime are the most frequently used and studied aerosolized antibiotics. This review summarizes the characteristics of aerosolized antibiotics, reviews the advantages and disadvantages of using aerosolized antibiotics, and calls for future investigations based on animal study data.

Topics: Administration, Inhalation; Amikacin; Animals; Anti-Bacterial Agents; Ceftazidime; Colistin; Humans; Pneumonia, Ventilator-Associated

The present meta-analysis and systematic review evaluated the efficacy and safety of aerosolized colistin as adjunctive therapy to i.v. antimicrobials or as monotherapy in the treatment of ventilator-associated pneumonia.. The databases of MEDLINE and Cochrane Library up to June 2013 and all reference lists of the included studies and relevant reviews were searched. Studies were eligible if the efficacy and safety of aerosolized colistin in the treatment of ventilator-associated pneumonia was evaluated. An overall effect estimate for all dichotomous data as an odds ratio with 95% CI was calculated by the Mantel-Haenszel or the DerSimonian and Laird method depending on the statistical heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to interpret the findings.. None.. Sixteen studies fulfilled the inclusion criteria: eight were comparing adjunctive aerosolized versus i.v. colistin (seven observational cohort or case-control studies and one randomized trial) and were meta-analyzed, and eight were single arm and were only systematically reviewed. The Grading of Recommendations Assessment, Development, and Evaluation approach showed limitations of the study design and presence of inconsistency in most of the outcomes, but no obvious indirectness or imprecision of results reporting. Based on the above assessments, the quality of evidence presented for each outcome ranged from "very low" to "low." A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14-2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11-2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34-0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to i.v. treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54-1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76-1.83; p = 0.45; I2 = 0%).. Based on the present results and awaiting further evidence from randomized trials, aerosolized colistin is associated with improved outcome in the treatment of ventilator-associated pneumonia although the level of evidence was low.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Clinical Trials as Topic; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Ventilator-Associated

Colistin has been used to treat nosocomial pneumonia (NP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) via different administration routes. Whether patients may benefit from aerosolised colistin as adjunctive treatment was contradictory. We aimed to clarify the safety and efficacy of administering aerosolised and intravenous (IV-AS) colistin versus intravenous (IV) colistin alone in patients with NP caused by MDR-GNB. Two reviewers independently evaluated and extracted data from PubMed, EMBASE and Cochrane databases. Primary outcomes were clinical response rate, all-cause mortality (ICU or hospital), microbiological eradication and nephrotoxicity. Pooled odds ratios (ORs) were calculated and significance was determined by the Z test. Nine eligible studies involving 672 participants were included. The overall clinical response rate (improvement and cure) was significantly higher in the IV-AS group than that in the IV group [OR=1.81, 95% confidence interval (CI) 1.30-2.53; P=0.0005]. Patients treated with IV-AS colistin showed a higher rate of pathogen eradication (OR=1.66, 95% CI 1.11-2.49; P=0.01) and lower all-cause mortality compared with IV colistin (OR=0.69, 95% CI 0.50-0.95; P=0.02). Nephrotoxicity did not differ significantly between IV-AS and IV groups (five studies; 383 patients) (OR=1.11, 95% CI 0.69-1.80; P=0.67). These data indicate that IV-AS colistin has additional benefits compared with IV colistin alone. Clinicians should be encouraged to give combined administration routes in critically ill patients with NP caused by MDR-GNB.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Nasal Sprays; Pneumonia, Ventilator-Associated; Treatment Outcome

Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) has emerged as an important and intractable clinical problem. This review assessed the efficacy and safety of colistin for treatment of MDR GNB VAP. PubMed and Embase were searched for controlled studies of colistin for treatment of MDR GNB VAP. The Mantel-Haenszel random-effects model was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was clinical cure; secondary outcomes were microbiological eradication, ICU mortality, hospital mortality, length of ICU stay and nephrotoxicity. Fourteen controlled studies involving 1167 patients were identified, including six reporting colistin versus β-lactam antibiotics, three reporting aerosolised (AS) plus intravenous (IV) colistin versus IV colistin alone and five reporting colistin combined therapy versus colistin monotherapy. The clinical cure rate of colistin was comparable with that of β-lactam antibiotics (OR=1.00, 95% CI 0.68-1.47). Compared with IV colistin alone, AS plus IV colistin exhibited a better clinical cure (OR=2.12, 95% CI 1.40-3.20). Compared with colistin monotherapy, colistin combined therapy did not appear to provide a better clinical cure (OR=1.38, 95% CI 0.81-2.33). There was no significant difference in nephrotoxicity and other secondary outcomes between the treatment groups. Colistin appears as effective and safe as β-lactam antibiotics for the treatment of MDR GNB VAP. AS colistin may be a beneficial adjunct to IV colistin in the management of MDR GNB VAP. Colistin combined therapy does not appear to provide better outcomes compared with colistin monotherapy.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP.. We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I(2) method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates.. Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI], .74-1.77; P = .56; I(2) = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI, .48-1.66; P = .71; I(2) = 0%]; retrospective OR, 1.45 [95% CI, .79-2.68; P = .23; I(2) = 0%]); randomized trials OR, 0.86 [95% CI, .43-1.74; P = .68; I(2) = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P = .95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). Fourteen single-arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies.. Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP.

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Lower respiratory tract infections, due to Pseudomonas aeruginosa or Acinetobacter baumannii, are frequently encountered in patients with cystic fibrosis (CF) or in patients developing nosocomial pneumonias. Both of these conditions bear a high mortality risk and aggressive antibiotic therapy is necessary. Inhaled antibiotics might represent an effective therapeutic approach for these diseases as it has demonstrated good bactericidal efficacy and safety in both preclinical and clinical studies. This colistin formulation might be useful particularly in patients with respiratory tract infections due to multidrug-resistant Gram-negative bacteria. Its main advantages are a better safety profile with a minimal or absent risk of nephrotoxicity.. This paper discusses the available systemic formulations of colistin, with pharmacokinetic and safety profiles, followed by an overview of inhaled antibiotics in lower respiratory tract infections.. Inhaled colistin should be used selectively as monotherapy in chronic infections with P. aeruginosa in CF patients, whereas in patients with hospital/ventilator-acquired pneumonia (HAP/VAP), it should be used in a combined regimen with systemic antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Animals; Anti-Bacterial Agents; Bronchiectasis; Colistin; Cross Infection; Cystic Fibrosis; Drug Synergism; Drug Therapy, Combination; Humans; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections

Hospital-acquired pneumonia is a common complication that continues to have a poor cure rate in some patients with intravenous therapy alone. Aerosolized antibiotics are theoretically attractive in an attempt to optimize lung concentrations of antibiotics. Limited data suggest that aerosolized aminoglycosides or colistin in addition to intravenous therapy results in good response rates in patients with multidrug-resistant organisms or nonresponding pneumonia. Adverse events can occur, especially with colistin. When used, care should be taken to properly compound and administer aerosolized antibiotics to ensure tolerability and good drug delivery.

Topics: Administration, Inhalation; Aerosols; Aminoglycosides; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Administration Schedule; Drug Dosage Calculations; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Lung; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

The administration of antibiotics by the inhaled route is a widely recognized treatment in patients with cystic fibrosis (CF) and bronchiectasis. Tobramycin solution for inhalation (TOBI) has been available for many years and is licensed in the USA and Europe. While strong data support the use of aerosolized antibiotics for the treatment of respiratory infections in patients with CF or bronchiectasis, only a few clinical studies have examined the role of aerosolized antibiotics in the treatment of pneumonia, including ventilator-associated pneumonia (VAP) in these patients. During the last decade increasing interest has been directed towards alternative treatments to the systemic administration of antimicrobial agents for the treatment of patients with hospital-acquired pneumonia or VAP due to multidrug-resistant (MDR) Gram-negative bacteria. Recent publications demonstrate the clinical benefits from administering inhaled aminoglycosides or polymyxins in patients with hospital-acquired pneumonia or VAP. In addition to antibiotics, antifungals, and antivirals have been administered by inhalation to specific groups of critically ill patients. However, randomized controlled trials dealing with the administration of anti-infective agents via the respiratory tract are necessary in order to validate the efficacy, safety, advantages, and disadvantages of this therapeutic approach for the treatment of nosocomial pneumonia.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Cross Infection; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic

The emergence of gram-negative bacteria resistant to most available antibiotics has led to the readministration of polymyxins B and E (colistin) as "salvage" therapy in critically ill patients. Recent studies demonstrated acceptable effectiveness and considerably less toxicity than reported in older studies of polymyxins. These old antibiotics may be administered for the treatment of intensive care unit-acquired infections of various types, including ventilator-associated pneumonia, urinary tract infections, bacteremia, and meningitis caused by multidrug resistant gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter species. Randomized controlled trials are urgently needed to further clarify various issues regarding the effectiveness and safety of polymyxins, however.

Topics: Anti-Bacterial Agents; Colistin; Critical Care; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Pneumonia, Ventilator-Associated; Polymyxin B

Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii.. This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician.. The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died.. The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Fosfomycin; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tobramycin; Treatment Outcome

An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC.. The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046.. Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group.. Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains.. Entasis Therapeutics and Zai Lab.

Topics: Acinetobacter baumannii; Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Cilastatin, Imipenem Drug Combination; Colistin; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis

Management of ventilator-associated pneumonia (VAP) is a puzzling issue for infectious disease specialist. The present clinical trial study was aimed to comparing the effects of injectable colistin plus nebulized colistin and injectable colistin plus nebulized tobramycin on management of patients with VAP due to multidrug-resistant Acinetobacter. VAP patients were randomly divided into two groups (

Topics: Acinetobacter; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Tobramycin

Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined.. A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved.. A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015).. This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.. ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

Topics: Aged; Anti-Bacterial Agents; Colistin; Equivalence Trials as Topic; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Colistin; Creatinine; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Healthcare-Associated Pneumonia; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sample Size; Sisomicin

In clinical practice, colistin is used as combination therapy to improve its antibacterial activity, despite the consequent increase in toxicity. This prospective, comparative study evaluated the effectiveness and adverse effects of using colistin alone at a loading dose of 9 million international units (MIU) followed by 3 MIU every 8h (q8h) versus colistin+meropenem 1g q8h in treating multidrug-resistant (MDR) Klebsiella pneumoniae-induced hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). The primary outcome measure was in-hospital mortality. The secondary measure was the occurrence of colistin toxicity.. A total of 60 patients were divided into two groups (30 patients each); the first group received intravenous colistin at a mean daily dose of 8.304 MIU and the second group received colistin 8.58 MIU combined with meropenem (mean daily dose of 2.88g for 15 days).. The colistin-meropenem combination group showed a significant decrease in mortality versus colistin alone [16.7% (5/30) vs. 43.3% (13/30); P=0.047]. The improved clinical response mediated by combination therapy was not associated with any significant nephrotoxicity, hepatotoxicity or neurotoxicity. Moreover, the 42 surviving patients showed normal procalcitonin values associated with a decrease in SOFA score, whilst 12 of them showed significantly elevated C-reactive protein (CRP) (P=0.0002).. This study revealed the superiority of colistin-meropenem combination therapy over colistin monotherapy in the treatment of MDR K. pneumoniae-induced HAP or VAP and highlights the advantage of procalcitonin over CRP as a marker for eradication of sepsis and suspension of therapy.

Topics: Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Healthcare-Associated Pneumonia; Humans; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies

Efficacy of colistin and ampicillin-sulbactam have not been compared in treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of colistin and ampicillin-sulbactam in combination with meropenem were compared in treatment of ventilator-associated pneumonia due to carbapenem-resistant A. baumannii.. 47 patients with ventilator-associated pneumonia due to carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological responses and 28-day mortality were considered as outcomes.. Clinical response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p = 0.59) were comparable between meropenem/colistin and meropenem/ampicillin-sulbactam groups, respectively.. In this study, clinical and microbiological response were comparable between the meropenem/colistin and meropenem/ampicillin-sulbactam groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

This study examined the literature on the treatment of ventilator-associated pneumonia (VAP) using colistin or standard care (SC). Based on this clinical material, a meta-analysis was conducted and a non-inferiority test was performed. Studies were selected for inclusion based on the following criteria: (a) patients with VAP; (b) experimental arm based on intravenous or aerosolized colistin; and (c) control arm based on SC. The meta-analysis employed a fixed-effect model, and the endpoint was the rate of clinical response. No pre-specified non-inferiority threshold for the upper boundary of the 95% confidence interval was adopted; instead, the intention was to perform a retrospective evaluation of whether the threshold suggested by the results was acceptable on clinical grounds. In total, eight controlled studies were included. The pooled risk ratio was 1.019 for colistin compared with SC (95% confidence interval 0.895-1.16); this result corresponds to a non-significant 1.9% increase in cure rate with colistin compared with SC (range +16% to -10.5%). Heterogeneity was minimal (0%). The post-hoc non-inferiority threshold for colistin compared with SC was -10.5% in terms of relative cure rate (pooled risk ratio = 0.895). This margin was considered to be acceptable on clinical grounds. This analysis found that colistin can play a role in the treatment of VAP, particularly when given as a combination of aerosolized and intravenous drug.

Topics: Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.. In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.. The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28.. As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

Topics: Administration, Inhalation; Aged; Amikacin; Anti-Bacterial Agents; Colistin; Double-Blind Method; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated

The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.. This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.. The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.. NCT01732250 and 2012-004819-31; Pre-results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Greece; Humans; Israel; Italy; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

This study aims to analyze the mortality and the length of ICU stay (LOS) of A. baumannii VAP compared to respiratory colonization in patients with mechanical ventilation (MV).. A prospective cohort study was performed in an ICU of adult patients (February 2010-June 2011). One hundred patients on MV with A. baumannii in lower respiratory airways were recruited, and classified as VAP or airways colonization according to CPIS criteria, with a punctuation ≥6. LOS, 30-days mortality, A. baumannii bacteremia, and clinical features including antibiotic therapy were recorded. Multivariate analysis (linear and Cox regression) and survival analysis (Kaplan-Meier curves) were performed.. Fifty-seven VAP and 43 colonized A. baumannii patients were analyzed. Among the A. baumannii strains, 99% were non-susceptible to carbapenems and the MIC90 of colistin was 0.12 mg/l. Therapy was appropriate in 94.6% of VAP patients, most of them with colistin 6 MIU/day, although in 13 (23.6%) cases colistin was started 48 hours after the onset of VAP. Mortality was similar in both groups (VAP 24.6% vs. colonized 27.9%, p = 0.7). Bacteremia and acute kidney insufficiency were associated with decreased survival (p = 0.02 and p = 0.04, respectively) in VAP patients. LOS was 21.5 (11.5-42.75) vs. 9 (6-22) days for VAP and colonized patients (p = 0.004). VAP (p = 0.003) and age (p = 0.01) were independently related to a longer LOS.. Multidrug-resistant A. baumannii VAP treated with colistin does not have a different mortality compared to lower airways colonization, among patients on mechanical-ventilation, in a setting of high susceptibility to colistin of A. baumannii.

Topics: Acinetobacter baumannii; Adult; Bacteremia; Carbapenems; Colistin; Disease-Free Survival; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Humans; Male; Pneumonia, Ventilator-Associated; Prospective Studies; Survival Rate

Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB.. The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed.. Currently, there is no study being undertaken which analyzes empiric treatment of (VAP) with a suspicion of multi-resistance. Colistin, an off-patent antibiotic commercialized for more than 60 years, could widen the antibiotic alternatives for a high-mortality illness aggravated by antibiotic resistance.. This trial is registered with ClinicalTrials.gov (identifier: NCT01292031 ; registered on 29 June 2012) and EudraCT (identifier: 2010-023310-31; registered on 7 February 2011).

Topics: Anti-Bacterial Agents; Clinical Protocols; Colistin; Drug Resistance, Multiple, Bacterial; Europe; Gram-Negative Bacterial Infections; Humans; Incidence; Meropenem; Patents as Topic; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Time Factors; Treatment Outcome

We evaluated whether prophylactic nebulised colistin could reduce ventilator-associated pneumonia (VAP) rates in an intensive care unit (ICU) setting with prevalent multidrug-resistant (MDR) bacteria.We used a single-centre, two-arm, randomised, open-label, controlled trial in a 12-bed ICU in the University Hospital of Larissa, Greece. Patient inclusion criteria included mechanical ventilation of >48 h. The two arms consisted of prophylaxis with 500 000 U colistin (Col group) or normal saline (NS group), thrice daily, for the first 10 ICU days or until extubation. The primary outcome of the study was the 30-day VAP incidence.In total, 168 patients entered the study. VAP incidence was not different between Col and NS group patients (14 (16.7%) versus 25 (29.8%), respectively, p=0.07). Regarding the secondary outcomes, the intervention resulted in a lower VAP incidence density rate (11.4 versus 25.6, respectively, p<0.01), and less Gram-negative bacteria-VAP (p=0.03) and MDR-VAP (p=0.04). Among VAP patients (n=39), prophylaxis with inhaled colistin improved ICU survival (p=0.016). There was no evidence of increased resistance to colistin or multidrug resistance.Our findings suggest that nebulised colistin had no significant effect on VAP incidence.

Topics: Administration, Inhalation; Adult; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Treatment Outcome

The aim of this study was to compare the responses of colistin treatment alone vs. a combination of colistin and rifampicin in the treatment of ventilator-associated pneumonia (VAP) caused by a carbapenem-resistant A. baumannii strain. Forty-three patients were randomly assigned to one of two treatment groups. Although clinical (P = 0·654), laboratory (P = 0·645), radiological (P = 0·290) and microbiological (P = 0·597) response rates were better in the combination group, these differences were not significant. However, time to microbiological clearance (3·1 ± 0·5 days, P = 0·029) was significantly shorter in the combination group. The VAP-related mortality rates were 63·6% (14/22) and 38·1% (8/21) for the colistin and the combination groups (P = 0·171), respectively. Our results suggest that the combination of colistin with rifampicin may improve clinical and microbiological outcomes of VAP patients infected with A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Rifampin; Treatment Outcome

Cases of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa are common in hospitalized patients at Siriraj Hospital, Bangkok, Thailand. Parenteral colistimethate sodium (CMS) has been used for therapy of VAP caused by MDR A. baumannii and P. aeruginosa at Siriraj Hospital over the past few years, with modest favourable outcomes. Objectives To determine whether nebulized CMS as adjunctive therapy of Gram-negative VAP was safe and beneficial.. This was a randomized controlled study in 100 adults who developed Gram-negative VAP (clinical trial registration number: NCT00920270). All patients received systemic antibiotics according to the decisions of their responsible physicians. The patients were randomized to receive an additional 4 mL of nebulized sterile normal saline (NSS) (n = 49) or nebulized CMS equivalent to 75 mg of colistin base in 4 mL of NSS (n = 51) every 12 h until systemic antibiotic therapy of VAP was ended.. The baseline characteristics of the patients and conventional therapy of VAP in both groups were comparable. Most of the cases of VAP were caused by MDR A. baumannii and/or P. aeruginosa. All isolates of Gram-negative bacteria were susceptible to colistin. Favourable clinical outcome was 51.0% in the CMS group and 53.1% in the control group (P = 0.84). Patients in the CMS group had significantly more favourable microbiological outcome when compared with patients in the control group (60.9% versus 38.2%, P = 0.03). Bronchospasm was observed in 7.8% of patients in the CMS group and in 2.0% of patients in the control group (P = 0.36). Renal impairment was observed in 25.5% of patients in the CMS group and in 22.4% of patients in the NSS group (P = 0.82).. Nebulized CMS as adjunctive therapy of Gram-negative VAP seems to be safe. However, a beneficial effect on clinical outcomes of adjunctive nebulized CMS for therapy of Gram-negative VAP was not ascertained.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance.. A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).. Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Susceptibility; Humans; Intensive Care Units; Pneumonia, Ventilator-Associated; Prevalence; Renal Dialysis; Retrospective Studies

Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated.. This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model.. During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis.. This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefiderocol; Colistin; COVID-19; Fosfomycin; Humans; Pneumonia, Ventilator-Associated

Hospital infections such as ventilator-associated pneumonia (VAP) due to multidrug-resistant Klebsiella pneumoniae (MDR-KP) strains have increased worldwide. In addition, biofilm production by these resistant isolates has confronted clinicians with higher treatment failure and infection recurrence. Given the paucity of new agents and limited data on combination therapy for MDR-KPs, the present study sought to evaluate the in vitro activity of several antibiotic combinations against planktonic and biofilm MDR-KPs isolated from patients with VAP.. All 10 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates demonstrated multidrug resistance against the tested antibiotics. At planktonic mode, combinations of colistin-meropenem and amoxicillin/clavulanate in combination with meropenem, colistin, or amikacin showed synergism against 60-70% isolates. On the other hand, in the biofilm state, colistin-based combinations exhibited synergism against 50-70% isolates and the most effective combination was colistin-amikacin with 70% synergy.. The results revealed that combinations of amoxicillin/clavulanate with colistin, meropenem, or amikacin in the planktonic mode and colistin with amoxicillin/clavulanate, meropenem, or amikacin in the biofilm mode could effectively inhibit CRKP isolates, and thus could be further explored for the treatment of CRKPs.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Colistin; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Topics: Aminoglycosides; Anti-Bacterial Agents; Colistin; Delivery of Health Care; Gram-Negative Bacteria; Humans; Pneumonia, Ventilator-Associated

Resistant strains of Pseudomonas aeruginosa are common pathogens in the intensive care unit (ICU), limiting available therapeutic options. We aimed to compare ceftolozane/tazobactam (C/T) with colistimethate sodium (CMS) in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. A retrospective, observational study was performed at a tertiary care ICU. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. A total of 51 patients were included (18 in the C/T and 33 in the CMS group). Clinical success rates in the C/T and CMS groups were 13 (72.2%) and 10 (30.3%), respectively. On multivariate regression analysis, treatment with C/T was independently associated with clinical success (odds ratio 4.47, 95% CI 1.17-17.08). There was no difference in 28-day all-cause mortality (27.8% and 33.3% in the C/T and CMS group, p = 0.76). Acute kidney injury was more common in patients who received CMS (48.5% vs 11.1%, p = 0.01). In our study, ceftolozane/tazobactam was more efficacious in the treatment of XDR Pseudomonas aeruginosa VAP and showed a better safety profile compared to CMS.

Topics: Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%,

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Cephalosporins; Colistin; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis

There has been accumulating interest in nebulised colistin methanesulfonate (CMS) for the treatment of ventilator-associated pneumonia (VAP). In this study, pulmonary and systemic pharmacokinetics following nebulisation of CMS at a dose of 3 MIU and 5 MIU, using a vibrating mesh nebuliser, for VAP caused by extensively drug-resistant Gram-negative pathogens was assessed. Blood samples and mini-bronchoalveolar lavage (mini-BAL) was performed post-dose at 1, 4 and 8 h. Concentrations of CMS and formed colistin in mini-BAL and plasma were determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis was conducted using a population approach. The study population included three groups (n = 10 per group): (A) intravenous CMS and concomitantly nebulised CMS at a dose of 3 MIU (30 min duration); (B) nebulised CMS at a dose of 3 MIU (30 min duration) as monotherapy; and (C) nebulised CMS 5 MIU (45 min duration) as monotherapy. Mean plasma formed colistin concentrations were <1 mg/L following CMS nebulisation as monotherapy (groups B and C). Predicted trough concentrations of formed colistin in the epithelial lining fluid (ELF) following 24-h dosing of 3 MIU and 5 MIU nebulised CMS were 120.4 mg/L and 200.7 mg/L, respectively. The model predicted that concomitant intravenous CMS (group A) had minimal impact on the formed colistin concentration in ELF. This study demonstrated high ELF formed colistin concentrations following nebulised CMS (constantly above colistin MICs), while plasma concentrations were lower than those associated with nephrotoxicity. Our results provide important information for optimisation of nebulised colistin therapy.

Topics: Anti-Bacterial Agents; Colistin; Humans; Lung; Mesylates; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Colistin; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated

The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia.. A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups.. A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000).. For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Topics: Anti-Bacterial Agents; Antipyretics; Cohort Studies; Colistin; Gram-Negative Bacteria; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Healthcare-Associated Pneumonia; Hospitals; Humans; Pneumonia, Ventilator-Associated

To compare the effectiveness and safety of aerosolized (AER) plus intravenous (IV) colistin with IV colistin alone in patients with nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative bacteria.. This was a retrospective cohort study of adults with NP who received IV colistin alone or in combination with AER colistin. The primary endpoint was clinical cure at end of therapy. Secondary endpoints included microbiological eradication, in-hospital mortality and nephrotoxicity.. In total, 135 patients were included in this study: 65 patients received AER plus IV colistin and 70 patients received IV colistin alone. Baseline characteristics were similar between the two groups. Clinical cure was achieved in 42 (65%) patients who received AER plus IV colistin and 26 (37%) patients who received IV colistin alone (P = 0.01). Among a total of 88 patients who were microbiologically evaluable, 27 (42%) patients who received AER plus IV colistin and 12 (17%) patients who received IV colistin alone attained favourable microbiological outcomes (P = 0.022). In-hospital mortality (43% vs 59%, P = 0.072) was higher in patients who received IV colistin alone, but the difference was not significant. Renal injury occurred in 31% of patients who received AER plus IV colistin and in 41% of patients who received IV colistin alone (P = 0.198).. AER colistin can be considered as salvage therapy as an adjunct to IV administration for the treatment of patients with NP due to MDR Gram-negative pathogens.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Healthcare-Associated Pneumonia; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

This study aimed to investigate the mechanisms of colistin resistance in 64 Acinetobacter baumannii isolates obtained from patients with ventilator-associated pneumonia hospitalised in Greece, Italy and Spain. In total, 31 A. baumannii isolates were colistin-resistant. Several novel amino acid substitutions in PmrCAB were found in 27 colistin-resistant A. baumannii. Most substitutions were detected in PmrB, indicating the importance of the histidine kinase for colistin resistance. In two colistin-resistant isolates, 93 amino acid changes were observed in PmrCAB compared with A. baumannii ACICU, and homologous recombination across different clonal lineages was suggested. Analysis of gene expression revealed increased pmrC expression in isolates harbouring pmrCAB mutations. Complementation of A. baumannii ATCC 19606 and ATCC 17978 with a pmrAB variant revealed increased pmrC expression but unchanged colistin MICs, indicating additional unknown factors associated with colistin resistance. Moreover, a combination of PmrB and PmrC alterations was associated with very high colistin MICs, suggesting accumulation of mutations as the mechanism for high-level resistance. The pmrC homologue eptA was detected in 29 colistin-susceptible and 26 colistin-resistant isolates. ISAba1 was found upstream of eptA in eight colistin-susceptible and one colistin-resistant isolate and eptA was disrupted by ISAba125 in two colistin-resistant isolates. Whilst in most isolates an association of eptA with colistin resistance was excluded, in one isolate an amino acid substitution in EptA (R127L) combined with a point mutation in ISAba1 upstream of eptA contributed to elevated colistin MICs. This study helps to gain an insight into the diversity and complexity of colistin resistance in A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Greece; Humans; Pneumonia, Ventilator-Associated

Topics: Aminoglycosides; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Coinfection; Colistin; COVID-19; Drug Resistance, Bacterial; Humans; Models, Theoretical; Pneumonia, Ventilator-Associated

Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates.. This retrospective matched case-control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone.. Both groups had similar MDR-GNB isolates and. With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Infant, Newborn; Infusions, Intravenous; Male; Pneumonia, Ventilator-Associated; Pregnancy; Respiration, Artificial; Retrospective Studies; Severity of Illness Index; Treatment Outcome

To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).. Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.. Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed.. In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies

Acinetobacter baumannii has evolved in recent decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in intensive care units (ICUs). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant A. baumannii. We retrospectively evaluated the potential efficacy, in terms of clinical and microbiological cure and mortality, of a combination of intravenous colistin and high-dose ampicillin/sulbactam and high-dose tigecycline, concurrently administered with inhaled colistin, in 10 ICU patients with ventilator-associated pneumonia (VAP) caused by carbapenem- and colistin-resistant A. baumannii strains, with high tigecycline MICs > 2μg/mL. Nine patients (90%) exhibited a successful clinical outcome, accompanied by microbiological eradication in seven of them. All clinically cured patients survived at 14 and 28 days. Acute kidney injury (AKI) was observed in one patient. In view of the increasing prevalence of pan-drug resistant A. baumannii infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, we feel that there is an emerging need for our results to be further validated in larger prospective studies.

Topics: Acinetobacter baumannii; Administration, Inhalation; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Drug Resistance, Multiple, Bacterial; Female; Humans; Injections, Intravenous; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Tigecycline

Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS.. A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed.. The mass median aerodynamic diameters were 1.4 ± 0.2 versus 0.9 ± 0.2 μm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) μg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume.. Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Anti-Bacterial Agents; Colistin; Cross-Over Studies; Drug Resistance, Multiple, Bacterial; Female; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Prospective Studies; Young Adult

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan-drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan-drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

Topics: Acute-Phase Proteins; Aged; Anti-Bacterial Agents; Cephalosporins; Colistin; Drug Resistance, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Few studies have compared nebulized and intravenous (IV) colistin for multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa pneumonia. This study compared the nephrotoxicity and clinical outcomes for these two delivery routes.. This study retrospectively compared 95 critically ill surgical patients who were diagnosed with Acinetobacter baumannii ventilator associated pneumonia and received colistin between March 2013 and January 2016.. The most common diagnoses were brain hemorrhage (27.4%), traumatic brain injury (20%), traumatic thoracic injury (15.8%), and secondary peritonitis (11.6%). Compared to the IV group, the nebulizer group was significantly older (60.0 vs. 67.5years, p=0.010), had higher APACHE II scores (16.3 vs. 19.9, p=0.001), and more frequently had diabetes mellitus (6.8% vs. 21.6%, p=0.043). Nephrotoxicity was more common in the IV group (60.5% vs. 15.7%, p<0.0001). Both groups had similar microbiological and clinical outcomes (p=0.921 and p=0.719, respectively). Patients with nephrotoxicity exhibited prolonged IV or nebulized colistin treatment and more frequent combination with vancomycin. Nephrotoxicity was independently associated with IV delivery (odds ratio: 8.48, 95% confidence interval: 2.95-24.39, p<0.0001).. Nebulized colistin may have less nephrotoxicity and provide similar clinical results, compared to IV colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii).. This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed.. Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin.. Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Chemotherapy, Adjuvant; Colistin; Cross Infection; Drug Therapy, Combination; Edetic Acid; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Thienamycins

Optimal dosing for nebulized colistin methanesulfonate (CMS), the prodrug of colistin, is unknown. We describe the pulmonary and systemic pharmacokinetics of CMS and colistin following nebulization of 0.5 million IU (MIU) of CMS in ventilated patients.. Twelve critically ill patients received 0.5 MIU of CMS administered every 8 h as 30 min nebulizations. Blood samples were collected immediately before and until 8 h after first nebulization; mini-bronchoalveolar lavage (mini-BAL) was performed at 1 and 5 h or 3 and 8 h (six patients each) post-dose. Pharmacokinetic analysis was performed for CMS and colistin plasma concentrations using a non-compartmental method. ClinicalTrials.gov: NCT01060891.. After nebulization, CMS concentrations in epithelial lining fluid (ELF) were much higher (100- to 1000-fold) than those in plasma. Concentrations of colistin in ELF should be considered with caution because when <6 mg/L in BAL, colistin bound to mini-BAL devices. Nevertheless, CMS and colistin concentrations in ELF were much lower than expected from previous results with a 2 MIU dose. From CMS plasma pharmacokinetics it was shown that CMS systemic bioavailability was only slightly decreased for the 0.5 MIU dose compared with 2 MIU.. This study shows that CMS concentrations were much higher (100- to 1000-fold) in ELF than in plasma after a 0.5 MIU aerosol of CMS, but much lower (10-fold) than expected from previous results with a 2 MIU dose. Therefore, until new pharmacokinetic and pharmacodynamic assessments of the treatment of ventilator-associated pneumonia with nebulized CMS are performed, the 2 MIU dose should be preferred to the 0.5 MIU dose.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated

Topics: Aged; Amikacin; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Immunocompromised Host; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Ventilators, Mechanical

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

We present the case of a patient with ventilator-associated pneumonia (VAP) caused by a pan-resistant Acinetobacter baumannii successfully treated with the combination colistin plus vancomycin plus rifampin, whose in vitro activity was investigated by checkerboard method and killing testing. Furthermore, the serum bactericidal activity (SBA) was assessed. Our case shows that an innovative regimen consisting of colistin plus antimicrobials active only against Gram-positive microorganisms might represent a valid therapeutic option for severe infections caused by colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Microbial Sensitivity Tests; Neurosurgical Procedures; Pneumonia, Ventilator-Associated; Rifampin; Subarachnoid Hemorrhage; Vancomycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam

In the present study 60 samples were collected from lower respiratory tract of patients suffering from Ventilator Associated Pneumonia (VAP) admitted in surgical and medical Intensive Care Units (ICUs) of Khyber Teaching Hospital, Peshawar, Pakistan. Recovered pathogens were characterized and their susceptibility pattern against commonly used antibacterial agents investigated. Most frequent bacterial pathogen found was methicillin- resistant Staphylococcus aureus (MRSA) (40%) followed by members of Enterobacteriaceae (22%; of which Escherichia coli (50%), Klebsiella pneumonia (30%), Enterobacter cloacae (10%) and Citrobacter freundii (10%), Pseudomonas aeruginosa 20% and Acinetobacter baumannii 18%. Majority of the specimens yielded polymicrobial growth (85.75% polymicrobial growth compared to 14.25% specimens yielding monomicrobial growth). The susceptibility pattern showed that A. baumannii was the most resistant bacterial pathogen. Based on the results of susceptibility pattern obtained in the present study, combination of linezolid with meropenem and colistin has been found to be the best combination option for empirical therapy for VAP pathogens in this region.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Case-Control Studies; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Linezolid; Male; Meropenem; Microbial Sensitivity Tests; Pakistan; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sputum; Trachea

Colistin loading dose (LD) has been postulated as an advance in therapy. The clinical, microbiological effectiveness and nephrotoxicity of adding an LD to systemic colistin in ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remain unknown. In this quasi experimental study, the efficacy, outcomes and nephrotoxicity in 30 adults who received intravenous colistin with LD for MDR A. baumannii ventilator associated pneumonia were compared with 22 in absence of LD. Adding LD, the clinical cure rate at 14 days of therapy increased from 47.6% to 56.7% (p>0.397). No significant differences in bacteriological clearance (80 vs 81%), ICU mortality (50% vs 54.2%) or ICU length of stay (median: 32 vs 36 days) were identified. Mortality increased (76.2% vs 35.5%, p=0.004) in patients with nephrotoxicity, with age (median 67.0 vs. 50.0 years, p=0.002) being the only risk factor for nephrotoxicity. The nephrotoxicity rate increased from 27.3% in absence of LD to 35.3% with LD and SOFA <8, and 69.2% (p= 0.065) with LD and SOFA >7. Overall, nephrotoxicity was more severe in the LD group according to RIFLE criteria (p=0.015). Adding LD to systemic colistin for MDR A. baumannii VAP had no significant effect on clinical cure rates, bacteriologic clearance or pre-defined outcomes. However, the nephrotoxicity rate increased with LD, with special risk in adults with high organ failure development or advanced age. Further evidence regarding the risks and benefits of LD is required. The development of newer agents and strategies is urgently needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis; Young Adult

In the present study, our objective was to evaluate and compare the clinical and microbiological results in patients receiving systemic and systemic plus inhaled colistin therapy due to nosocomial pneumonia (NP) or ventilator associated pneumonia (VAP) caused by Acinetobacter baumannii.. A retrospective matched case-control study was performed at the ICUs at Izmir Katip Celebi University Ataturk Training and Research Hospital from January 2013 to December 2014. Eighty patients who received only systemic colistin were matched 43 patients who received systemic colistin combined with inhaled therapy.. In 97.6 % of the patients colistin was co-administered with at least one additional antibiotic. The most frequently co-administered antibiotics were carbapenems (79.7 %). The patient groups did not differ significantly in terms of the non-colistin antibiotics used for treatment (p > 0.05). Acute renal injury was observed in 53.8 % and 48.8 % of the patients who received parenteral colistin or parenteral plus inhaler colistin, respectively (p = 0.603). There were no significant differences between the groups in terms of clinical success (p = 0.974), clinical failure (p = 0.291), or recurrence (p = 0.094). Only, a significantly higher partial clinical improvement rate was observed in the systemic colistin group (p = 0.009). No significant differences between the two groups in terms of eradication (p = 0.712), persistence (p = 0.470), or recurrence (p = 0.356) rates was observed. One-month mortality rate was similar in systemic (47.5 %) and systemic plus inhaled (53.5 %) treatment groups (p = 0.526).. Our results suggest that combination of inhaled colistin with intravenous colistin had no additional therapeutic benefit in terms of clinical or microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Cross Infection; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Young Adult

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Risk Factors; Survival Analysis; Tertiary Care Centers

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Pneumonia, Ventilator-Associated

Limited data exist regarding prognostic factors and optimal antimicrobial treatment of infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). This retrospective cohort study included 93 adult patients who developed ventilator-associated pneumonia (VAP) due to XDR-AB in the ICU of the University Hospital of Heraklion, Greece, from October 2012 to April 2015. XDR-AB isolates were mainly susceptible to colistin (93.5%) and tigecycline (25.8%), whereas 6 (6.5%) were pandrug-resistant. Prior to infection, patients had long durations of mechanical ventilation and hospital stay and multiple exposures to antibiotics. Median Charlson co-morbidity and APACHE II scores were 2 and 17, respectively. Mortality at 28 days of infection onset was high (34.4%) despite high rates of in-vitro-active empirical (81.7%) and definitive (90.3%) treatment. Active colistin-based combination therapy (n = 55) and monotherapy (n = 29) groups had similar 28-day mortality (27.6% vs. 30.9%, respectively) and Kaplan-Meier survival estimates over time. In multivariable Cox regression, advanced age (aHR = 1.05 per year increase, 95% CI 1.02-1.09), rapidly fatal underlying disease (aHR = 2.64, 95% CI 0.98-9.17) and APACHE II score (aHR = 1.06 per unit increase, 95% CI 0.99-1.14) were identified as independent predictors of 28-day mortality, but no difference in mortality hazards between the active colistin-based combination therapy and monotherapy groups was produced (aHR = 0.88, 95% CI 0.35-2.38). These results support the use of colistin as a first-line agent against VAP in settings where XDR-AB is endemic, but oppose the introduction of colistin-based combination therapy as standard treatment.

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Greece; Hospitals, University; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Prognosis; Retrospective Studies; Survival Analysis; Young Adult

There has been increased incidence and high mortality in cases with ventilator-associated pneumonia (VAP) caused by colistin-only-susceptible Acinetobacter baumannii (COS-AB). Colistin has emerged as a therapeutic option for VAP caused by multidrug-resistant Gram-negative organisms including COS-AB. A retrospective study was conducted to examine the impact of early versus late initiation of colistin on 30-day mortality of critically ill patients with VAP caused by COS-AB.. Critically ill patients with VAP caused by COS-AB who received colistin were enrolled. The receiver operating characteristic (ROC) curve was used to identify the temporal breakpoint that maximized the difference in 30-day mortality.. A total of 56 patients (34 men and 22 women) were included in the study. About 86% of all cases were late-onset VAP. The 30-day mortality was 46.4%. The rate was higher among patients with admission Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 18 and patients with a delay of more than four days in initiating colistin treatment. The mortality rate was 26.9% among patients with treatment delay of four or fewer days and 63.3% for patients with a treatment delay of more than four days.. A delay of four days or more in initiating colistin in patients with VAP caused by COS-AB significantly increases mortality. Colistin should be considered in the empirical protocols in late-onset VAP cases when COS-AB is highly suspected.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Female; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Survival Analysis; Time Factors; Young Adult

In the present study, we challenged the concept that levofloxacin should not be used for the management of ventilator-associated pneumonia (VAP) when minimum inhibitory concentrations (MICs) exceed 2 μg/ml. Multidrug-resistant (MDR) and genetically distinct isolates of Pseudomonas aeruginosa (n = 49) and Acinetobacter baumannii (n = 29) from patients with VAP were exposed over time to levofloxacin, imipenem, colistin and their combinations. Synergy between levofloxacin and imipenem was found in 55.3 % and between levofloxacin and colistin in 90.9 % of isolates of P. aeruginosa within the first 4 h of growth. Synergy with imipenem but not with colistin was dependent of the MIC. Synergy between levofloxacin and imipenem was found in 58.6 % of isolates of A. baumannii after 24 h of growth. Considerable synergy was found between levofloxacin and colistin, reaching 84.8 % of isolates of A.baumannii after 6 h of growth. Synergy was independent from the MIC. These results create hopes that levofloxacin can be used as combination therapy for infections by MDR bacteria.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Levofloxacin; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors

With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.. Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.. Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.. Colistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Ampicillin; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electronic Health Records; Electrophoresis, Gel, Pulsed-Field; Ethanolamines; Female; Humans; Lipid A; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Pneumonia, Ventilator-Associated; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulbactam

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

The objective of this study was to compare the safety and efficacy of inhaled plus intravenous (IV) colistin with that of IV colistin alone in critically ill children with ventilator-associated pneumonia (VAP) due to colistin-only susceptible (COS) Gram-negative bacteria (GNB).. This retrospective cohort study included critically ill children aged 1 month to 18 years with culture-documented monomicrobial VAP due to COS GNB.. Fifty patients were included, and 32 patients received IV colistin alone, whereas 18 patients received inhaled plus IV colistin. No between-cohort differences were observed in clinical (p = 0.49) and microbiological outcomes (p = 0.68), or VAP-related mortality (p = 0.99). Although the bacterial eradication rates did not differ in either treatment group, the median time to bacterial eradication (TBE) was significantly shorter in the inhaled plus IV colistin group than in the IV colistin group. The additional use of inhaled colistin was the only independent factor associated with TBE, and it shortened the median TBE by 3 days. Only one patient in the IV colistin group developed reversible nephrotoxicity. Mild bronchoconstriction was observed in three patients at the time of administration of the first doses of inhaled colistin, which did not require discontinuation of treatment.. The present study has demonstrated that the addition of inhaled colistin to IV colistin led to a shorter TBE in critically ill children with VAP due to COS GNB. However, it did not lead to a significant difference in the clinical and microbiological outcomes of VAP.

Topics: Administration, Inhalation; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Cohort Studies; Colistin; Critical Illness; Female; Humans; Infant; Male; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Colistin use has increased over the last ten years because of multidrug-resistant microorganisms. The aim of this study was to compare the clinical and microbiological efficacy of colistin alone or in combination with sulbactam or carbapenem in the treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) and extremely drug-resistant (XDR) A. baumannii.. Cases treated for VAP because of MDR and XDR A. baumannii between January 2011 and January 2013 were included in the study. The primary and secondary outcome for colistin alone, colistin with sulbactam, and colistin with carbapenems were evaluated. The primary outcomes were clinical efficacy and microbiological efficacy; the secondary outcomes were nephrotoxicity, length of hospitalization, and mortality.. A total of 70 VAP patients were evaluated. A total of 17 patients (24.3%) were administered colistin alone, 20 patients (28.6%) were administered colistin and sulbactam, and 33 patients (47.1%) were administered colistin and carbapenem. Clinical and microbiological response rates were higher in the carbapenem combination group (63.6% and 63.6% in both) than in the sulbactam combination group, which registered 55.0% and 60.0%, respectively. However, this did not represent a significant difference statistically (p > 0.05). There was also no significant difference between colistin alone and the combination groups regarding clinical and microbiological efficacy and mortality.. Neither the administration of colistin alone nor colistin combined with either sulbactam or carbapenem had any noticeable advantage in the treatment of VAP in terms of clinical response, microbiological response, nephrotoxicity, length of hospitalization, and mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Renal Insufficiency; Retrospective Studies; Sulbactam; Treatment Outcome

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii remains a significant cause of morbidity and mortality. Increasing antimicrobial resistance influences the selection of antibiotic treatment especially pandrug-resistant A. baumannii. A retrospective cohort study was conducted in the Medical Intensive Care Unit to identify the risk factors of VAP caused by multidrug-resistant A. baumannii (MDR-AB), extensively drug-resistant A. baumannii (XDR-AB) and pandrug-resistant A. baumannii (PDR-AB). All 337 adult patients with confirmed A. baumannii VAP were included. The incidence of MDR-AB, XDR-AB and PDR-AB were 72 (21.4%), 220 (65.3%) and 12 (3.6%), respectively. The risk factor for MDR-AB was prior use of carbapenems (OR 5.20; 95% CI 1.41-19.17). Risk factors for XDR-AB were the prior use of carbapenems (OR, 6.30; 95% CI, 1.80-21.97) and a high Sequential Organ Failure Assessment (SOFA) score (OR 1.35; 95% CI 1.07-1.71). In PDR-AB, the risk factors were the prior use of colistin (OR, 155.95; 95% CI, 8.00-3041.98), carbapenems (OR, 12.84; 95% CI, 1.60-103.20) and a high Simplified Acute Physiology Score (SAPS II) (OR 1.10; 95% CI 1.01-1.22). In conclusion, previous exposure to antibiotics and severity of VAP were risk factors of drug-resistant A. baumannii. Judicious use of carbapenems and colistin is recommended to prevent the antimicrobial-resistant strains of this organism.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Pneumonia, Ventilator-Associated; Retrospective Studies; Risk Factors; Thailand

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

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cluster Analysis; Colistin; Drug Synergism; Genotype; Hospitals; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pneumonia, Ventilator-Associated; Vietnam

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

Topics: Anti-Bacterial Agents; Colistin; Humans; Microbiota; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated

To compare clinical and microbiological efficacy of colistin and colistin/sulbactam for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii VAP in intensive care units (ICUs).. In this retrospective analysis, patients (>16 years-old) who received IV colistin or colistin/sulbactam for the treatment of MDR A. baumannii VAP were evaluated. The clinical and microbiological responses to therapies were assessed on the fifth day and at the end of the therapy.. During the study period, 89 patients were enrolled into the study. Fifty-two (58.4 %) patients received colistin and 37 (41.6 %) patients received colistin/sulbactam therapy. The median APACHE II score was higher and diabetes mellitus was more common in the colistin/sulbactam group (p < 0.05). However, other demographic characteristics were not statistically significant between groups. On the fifth day of colistin and colistin/sulbactam therapies, clinical response rates were 40.4 and 43.2 %, respectively. At the end of the therapies, clinical response rates were 29.8 and 40 %, respectively. The bacteriological response rates were 72.3 and 85.7 % in colistin and colistin/sulbactam groups, respectively. There were no statistically significant differences in clinical cure rates or bacteriological clearance rates between the two groups.. The colistin/sulbactam combination therapy is promising in severe MDR A. baumannii VAP. Although, the difference was not statistically significant, clinical cure rates or bacteriological clearance rates were better in the combination group than colistin monotherapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Treatment Outcome; Young Adult

A colistin-glycopeptide combination (CGC) has been shown in vitro to be synergistic against multidrug-resistant Gram-negative bacteria (MDR GNB), especially Acinetobacter baumannii, and to prevent further resistance. However, clinical data are lacking. We carried out a retrospective multicenter study of patients hospitalized in intensive care units (ICUs) who received colistin for GNB infection over a 1-year period, to assess the rates of nephrotoxicity and 30-day mortality after treatment onset among patients treated with and without CGC for ≥48 h. Of the 184 patients treated with colistin, GNB infection was documented for 166. The main causative agents were MDR A. baumannii (59.6%), MDR Pseudomonas aeruginosa (18.7%), and carbapenem-resistant Klebsiella pneumoniae (14.5%); in 16.9% of patients, a Gram-positive bacterium (GPB) coinfection was documented. Overall, 68 patients (40.9%) received CGC. Comparison of patients treated with and without CGC showed significant differences for respiratory failure (39.7% versus 58.2%), ventilator-associated pneumonia (54.4% versus 71.4%), MDR A. baumannii infection (70.6% versus 52%), and GPB coinfection (41.2% versus 0%); there were no differences for nephrotoxicity (11.8% versus 13.3%) and 30-day mortality (33.8% versus 29.6%). Cox analysis performed on patients who survived for ≥5 days after treatment onset showed that the Charlson index (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.44; P = 0.001) and MDR A. baumannii infection (HR, 2.51; 95% CI, 1.23 to 5.12; P = 0.01) were independent predictors of 30-day mortality, whereas receiving CGC for ≥5 days was a protective factor (HR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03). We found that CGC was not associated with higher nephrotoxicity and was a protective factor for mortality if administered for ≥5 days.

Topics: Acinetobacter baumannii; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Therapy, Combination; Female; Glycopeptides; Gram-Negative Bacterial Infections; Humans; Kidney; Klebsiella pneumoniae; Male; Middle Aged; Pneumonia, Ventilator-Associated; Proportional Hazards Models; Pseudomonas aeruginosa; Survival Analysis; Treatment Outcome

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

Topics: Anti-Bacterial Agents; Colistin; Female; Gram-Negative Bacteria; Humans; Male; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Colistin; Female; Gram-Negative Bacteria; Humans; Male; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Female; Humans; Male; Pneumonia, Ventilator-Associated

Topics: Acinetobacter baumannii; Acinetobacter Infections; Colistin; Female; Humans; Male; Pneumonia, Ventilator-Associated

Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients.

Topics: Administration, Inhalation; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biotransformation; Colistin; Critical Illness; Drug Administration Schedule; Drug Dosage Calculations; Extracellular Fluid; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Half-Life; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Statistical; Pneumonia, Ventilator-Associated

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii is increasing. It has a high mortality rate but experience in using inhaled colistin as monotherapy for VAP in children, especially pre-term infants, is limited. This study presents experiences using aerosolized colistin as monotherapy for VAP due to A. baumannii infection in pre-term infants.. Eight pre-term infants (gestational age 25-36 weeks) admitted to the neonatal intensive care unit (NICU) of Kaohsiung Chang Gung Memorial Hospital in Taiwan from January 2006 to December 2010 who received inhaled colistin as monotherapy for VAP due to A. baumannii infection were retrospectively evaluated. Of the isolated microorganisms, five were multi-drug resistant strains of A. baumannii (MDR-AB) but all were sensitive to colistin. All patients received inhaled colistin at a dose of 1,000,000 IU (33.4 mg) twice daily for an average of 9.1 days (range, 4-22 days).. All pre-term infants were cured, with A. baumannii eradicated from airway secretions. There were no clinical or laboratory adverse events related to colistin use.. Aerosolized colistin may be used as monotherapy for VAP due to A. baumannii infection in pre-term infants. A larger controlled study is warranted to corroborate the findings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pneumonia, Ventilator-Associated; Retrospective Studies

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Carbapenems; Colistin; Doripenem; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Ventilator-Associated; Treatment Outcome

The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP.. We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae.. Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission (P = .01) and combined AS-IV colistin therapy (P = .009). Higher mean Simplified Acute Physiology Score II (P = .002) and Sequential Organ Failure Assessment (P = .05) scores, septic shock (P < .001), and AKI onset during colistin treatment (P = .04) were independently associated with clinical failure.. Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.

Topics: Acinetobacter baumannii; Administration, Inhalation; Aged; Anti-Bacterial Agents; Case-Control Studies; Colistin; Critical Care; Female; Gram-Negative Bacteria; Humans; Injections, Intravenous; Klebsiella pneumoniae; Male; Middle Aged; Multivariate Analysis; Patient Safety; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Treatment Outcome; Ventilators, Mechanical

This study aimed to address the relationship between the timing of colistin therapy and the outcome, defined as all-cause mortality in the intensive care unit (ICU). A retrospective study was undertaken in a 16-bed ICU of a 750-bed tertiary care hospital. A total of 46 patients who had been administered intravenous colistin treatment for colistin-susceptible-only Acinetobacter infections were included in the study. Colistin treatment was initiated in 26 (56.5 %) patients within 24 h of the diagnosis (early administration of colistin), whereas the rest of the patients had obtained delayed treatment (delayed administration of colistin). Of the 46 patients, 21 (45.6 %) died. With univariate analysis, age, age greater than 65 years, APACHE II score more than 20 at baseline, and delayed administration of colistin were found to be significant (p < 0.05). Logistic regression analysis revealed a significant association between delayed administration of colistin [adjusted odds ratio (OR), 5.06; confidence interval (CI), 1.18-21.67], and adverse outcome. Other variables included in the final model were underlying disease (OR, 2.81; CI, 1.15-6.84) and APACHE II score at baseline >20 (OR, 3.81; CI, 0.77-18.75). This study found that delayed administration of colistin and underlying disease were independently associated with adverse outcome.

Topics: Acinetobacter Infections; Adult; Aged; Analysis of Variance; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

Multidrug-resistant (MDR) gram-negative bacteria-related nosocomial infections and ventilator-associated pneumonia (VAP) presents an emerging challenge to clinicians. Older antimicrobial agents such as colistin have become life-saving drugs because of the susceptibility of these pathogens. We report our experience with aerosolized colistin in two preterm and one term neonate with Acinetobacter baumannii and Pseudomonas aeruginosa-related VAP who were unresponsiveness to previous antimicrobial treatment. All pathogens were isolated from tracheal aspirate. We used 5 mg/kg (base activity) aerosolized colistin methanesulfonate sodium in every 12 h as an adjunctive therapy for VAP. VAP was treated by 14, 14, and 16-day courses of aerosolized colistin in these patients, respectively. No adverse effect such as nephrotoxicity or neurotoxicity was observed. We found that aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. Further studies are needed to determine appropriate doses for aerosolized colistin and its eligibility as an alternative treatment choice in newborns.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Topics: Carbapenems; Colistin; Cross Infection; Doripenem; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Time Factors

Topics: Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated

Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes.. To assess outcomes associated with AAA for the treatment of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) VAP.. A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009 were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA).. Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n = 9, inhaled tobramycin n = 10). Patients receiving AAA were significantly more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P < .001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P < .001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P = .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test).. Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage; Colistin; Comorbidity; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Statistics, Nonparametric; Survival Rate; Tobramycin; Treatment Outcome

Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Forecasting; Humans; Nasal Sprays; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Respiratory Tract Infections

In this study we aimed to assess the safety and efficacy of high-dose IV colistin (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator-associated pneumonia (VAP). Critically ill adult patients who received IV COL for multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of 45 patients were evaluated [15 patients with high-dose COL (2.5 mg/kg every 6 h), 20 patients with normal dose (2.5 mg/kg every 12 h), and 10 patients with low dose, determined according to creatine clearance]. Aerosolized COL was used in 29 patients treated with parenteral COL and 16 patients received only parenteral COL. The clinical response rates on the fifth day were 50, 30, and 27 % with the normal, low, and high doses, respectively. However, the clinical response rates at the end of the therapy had declined to 30, 30, and 7 % with the normal, low, and high doses, respectively. The bacteriological clearance rates at the end of the therapy were 65, 75, and 64 %, with the normal, low, and high doses, respectively. With the aerosolized COL, the clinical response rates on the fifth day and at the end of the therapy were 35 and 14 %, whereas these rates were 44 and 38 % without the aerosolized COL. Bacteriological clearance rates with and without the aerosolized COL were 76 and 69 %, respectively. The nephrotoxicity rate was 40 % for the high-dose COL, whereas it was 35 % for the normal dose, and 20 % for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL had no advantages over lower doses in alleviating multidrug-resistant A. baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the nephrotoxicity risk and seemed not to be safe.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Adult; Aerosols; Aged; Anti-Bacterial Agents; Chi-Square Distribution; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Diseases; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Statistics, Nonparametric; Turkey

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Female; Humans; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Tobramycin

Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.. One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to β-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n=28) or combined to a 3-day intravenous aminoglycosides for 7-19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer.. After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference -1%, lower limit of 95% CI for difference -12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients.. Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous β-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

Infections caused by extensive drug-resistant Acinetobacter baumannii (XDR-AB) have been increasingly observed and are associated with a high mortality rate. We present our experience using aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) due to XDR-AB in neonates.. The clinical data of neonates who received aerosolized 4 mg per kg of colistin base twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008 and September 2009 were retrospectively reviewed. The outcomes were compared with the neonates with VAP from XDR-AB in October 2006-September 2007 who did not receive aerosolized colistin.. During the study period, eight neonates (three preterm and five term neonates) with VAP caused by XDR-AB received aerosolized colistin. All isolated pathogens from the tracheobronchial specimens of the eight patients were XDR-AB susceptible to colistin only. Six patients received aerosolized colistin without concomitant intravenous colistin. All children were cured with eradication of XDR-AB from respiratory secretions. Seven patients survived and were discharged from the hospital, and one died from bacterial sepsis unrelated to the VAP episode. There were no clinical or laboratory adverse events related to aerosolized colistin. Compared to the seven neonates in the earlier period, the neonates who received aerosolized colistin had higher birth weight and gestational age, and lower mortality rate (13% vs. 71%, P=0.04).. Aerosolized colistin may be a useful adjunctive therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should be investigated in a larger controlled study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Bacteremia; Birth Weight; Colistin; Drug Resistance, Bacterial; Female; Gestational Age; Humans; Infant, Newborn; Male; Pneumonia, Ventilator-Associated; Retrospective Studies; Thailand; Treatment Outcome

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Europe; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Piperacillin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Quinolones; Respiration, Artificial; Severity of Illness Index; Treatment Outcome

Topics: Bronchoalveolar Lavage Fluid; Colistin; Critical Illness; Humans; Injections, Intravenous; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Colistin; Critical Illness; Humans; Pneumonia, Ventilator-Associated

To analyze the efficacy of nebulized colistin in the microbiological eradication and clinical improvement of patients with pulmonary infection by multi-resistant Acinetobacter baumannii (MAB).. A retrospective study.. Intensive Care Unit of a Tertiary hospital.. Hospitalized patients on invasive mechanical ventilation with positive MAB cultures of the airway.. All received treatment with colistin (CL). Nosocomial pneumonia (NP) or Tracheobronchitis (TB) was determined according to routine criteria and colonization (CO) was determined in the case of a positive culture in the absence of infection criteria. Three groups of patients were defined: those treated with nebulized CL, those treated with IV CL and those treated with IV CL plus nebulized CL.. Baseline characteristics. Microbiological eradication and clinical recovery were evaluated according to routine criteria.. 83 patients were studied, 54 of whom were treated, with the following diagnoses: 15 (27.8%) with NP, 16 (29.6%) with TB and 23 patients (42.6%) with CO. Nebulized CL was used in 36 patients (66.7%): 66.7% of which for CO, 33.3% in treatment for TB and in no case of NP. In 61.1% of the patients, IV CL was used: 22.2% of which for CO, 38.9% for TB and 38.9% in NP. The combination of IV CL and nebulized CL was used in 15 patients (27.8%): 5 patients (33.3%) CO, 2 patients (13.3%) TB and 8 patients (53.3%) NP. Microbiological eradication was achieved in 32 patients (59.3%), with the following distribution: 8 (47.1%) with IV CL, 15 (83.3%) with nebulized CL and 9 patients (69.2%) with a combination of IV CL and nebulized CL. Clinical recovery was achieved in 42 patients (77.8%): 12 (80%) with IV CL, 18 (94.7%) with nebulized CL and 12 (85.7%) with a combination of nebulized and IV CL. These differences were not significant. In the group of patients with infection due to TB and NP (31 patients, 57.4%), microbiological eradication was achieved in 5 patients (100%) treated with nebulized CL and in 6 of the 9 patients (42.9%) treated with IV CL, the difference being significant (P<.05). Clinical recovery in this group was 100% (6 patients) treated with nebulized CL and 75% (9 of the 12 patients) in the IV CL group. This difference was not significant.. Our study suggests that treatment with colistin in patients with pulmonary infection with multi-resistant Acinetobacter baumannii could be more efficient if it were to be administrated solely nebulized or in combination with IV colistin rather than administered solely intravenously.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Bronchitis; Colistin; Critical Illness; Cross Infection; Dose-Response Relationship, Drug; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Middle Aged; Nebulizers and Vaporizers; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Tracheitis; Tracheotomy

Topics: Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Topics: Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Humans; Pneumonia, Ventilator-Associated; Treatment Outcome

Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Colistin; Gram-Negative Bacterial Infections; Humans; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Statistics as Topic; Treatment Outcome

Ventilator-associated pneumonia (VAP) as a result of multidrug-resistant Gram-negative bacteria has contributed to the revival of the use of intravenous (i.v.) colistin. However, the additional administration of inhaled colistin for VAP is controversial. We performed a retrospective cohort study of patients with microbiologically documented VAP who received i.v. colistin with or without inhaled colistin. Seventy-eight patients with VAP received i.v. plus inhaled colistin, whereas 43 patients received i.v. colistin alone. The mean +/- SD daily dosage of i.v. colistin was 7.0 +/- 2.4 and 6.4 +/- 2.3 million international units (IU), respectively (p 0.13); the average daily dosage of inhaled colistin was 2.1 +/- 0.9 million IU. The outcome of infection was cure for 62/78 (79.5%) patients who received i.v. plus inhaled colistin vs. 26/43 (60.5%) patients who received i.v. colistin alone (p 0.025); all-cause in-hospital mortality was 31/78 (39.7%) vs. 19/43 (44.2%), respectively (p 0.63); all-cause intensive care unit (ICU) mortality was 28/78 (35.9%) vs. 17/43 (39.5%), respectively (p 0.92). The use of inhaled colistin was independently associated with the cure of VAP in a multivariable analysis (OR 2.53, 95% CI 1.11-5.76). Independent predictors of mortality were a higher APACHE II score (OR 1.12, 95% CI 1.04-1.20), presence of malignancy (OR 4.11, 95% CI 1.18-14.23) and lower daily dosage of i.v. colistin (OR 0.81, 95% CI 0.68-0.96). The outcome of VAP was better in patients who received inhaled colistin with i.v. colistin than those who received i.v. colistin alone. There was no difference in all-cause in-hospital and ICU mortality between the two groups. Randomized controlled trials are needed to evaluate further the role of inhaled colistin in VAP.

Topics: Administration, Inhalation; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Survival Analysis; Treatment Outcome

Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL.. In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis.. Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 μg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8)), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 μg × h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC(0-24)/MIC ratio (MIC = 2 μg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed.. Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen.

Topics: Adult; Aged; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Colistin; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Survival Rate; Treatment Outcome; Young Adult

Ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) Acinetobacter baumannii in critically ill patients presents an emerging challenge to clinicians. Administration of aerosolized colistin as an adjunctive therapy is one therapeutic option mentioned in limited evidence-based studies. This study aimed to evaluate the effectiveness of adjunctive aerosolized colistin treatment for VAP due to MDR pathogens.. We retrospectively reviewed the medical records of patients who had received aerosolized colistin for treatment of VAP due to MDR A. baumannii in our hospital from August to December 2008.. Forty-five patients were enrolled in our study. The mean age was 71 +/- 15 years. The mean Acute Physiological and Chronic Health Evaluation II (APACHE II) scores on the day of intensive care unit admission and on the first day of aerosolized colistin administration were 22.5 +/- 6.7 and 18.9 +/- 5.7, respectively. The mean duration of intensive care unit stay was 34 +/- 16 days. The mean daily dosage of aerosolized colistin was 4.29 +/- 0.82 million IU, and the mean duration of administration was 10.29 days. Seventeen patients (37.8%) had a favorable microbiological outcome and 26 (57.8%) showed a clinical response. Mortality due to all causes was 42.2%. No adverse effects related to inhaled colistin were recorded.. Aerosolized colistin may be considered as an adjunct to intravenous treatments in patients with VAP due to colistin-susceptible MDR A. baumannii in critically ill patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Hospitals; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Taiwan; Treatment Outcome

To report a case of recurrent Stenotrophomonas maltophilia ventilator-associated pneumonia (VAP) that was successfully treated with doxycycline and aerosolized colistin.. A 28-year-old male was admitted with a severe head injury and required mechanical ventilation. The patient developed S. maltophilia VAP on hospital day 17, which was cured after 7 days of treatment with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). However, on day 34, the patient developed recurrent S. maltophilia VAP that did not respond clinically or demonstrate eradication on follow-up culture after 10 days of TMP/SMX. At that time, TMP/SMX was discontinued and treatment was initiated with intravenous doxycycline and aerosolized colistin. The VAP episode was cured after 14 days of treatment with doxycycline/aerosolized colistin.. S. maltophilia is an emerging cause of VAP in some centers. This organism is associated with high mortality rates and has few treatment options because it is intrinsically resistant to most drug classes. Recent data suggest that doxycycline and aerosolized colistin each are effective in treatment of other multidrug-resistant organisms, such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, this is the first report describing the use of this antibiotic regimen for S. maltophilia. High-dose TMP/SMX is considered to be the drug of choice primarily based on excellent in vitro activity. Few data exist on how to treat patients who fail therapy with TMP/SMX or cannot receive that drug because of resistance, allergy, or adverse events. Thus, it is important to report alternative methods for treating this infection.. The positive clinical response to doxycycline and aerosolized colistin seen in the patient described here suggests that this combination may be an alternative treatment in patients who fail initial treatment or cannot receive standard therapies.

Topics: Administration, Inhalation; Adult; Aerosols; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) organisms is increasing. Intravenous (IV) colistin or aerosolized (AS) plus IV colistin have been recently used to treat these life-threatening infections. The purpose of this study was to compare the efficacy and safety of AS plus IV colistin versus IV colistin alone for patients with MDR VAP due to gram-negative bacteria.. A retrospective matched case-control study was performed at the Intensive Care Unit of the University Hospital of Heraklion, Greece, from January 2005 through December 2008. Forty-three patients with VAP due gram-negative MDR pathogens received AS plus IV colistin and were matched on the basis of age and Acute Physiology and Chronic Health Evaluation II score with 43 control patients who had received IV colistin alone.. Demographic characteristics, clinical status, and gram-negative isolated pathogens were similar between the 2 treatment groups. Acinetobacter baumannii (66 cases [77%]) was the most common pathogen, followed by Klebsiella pneumoniae (12 cases [14%]) and Pseudomonas aeruginosa (8 cases [9.3%]). No colistin-resistant strains were isolated from patients in either group. No significant differences between the 2 groups were observed regarding eradication of pathogens (P = .679), clinical cure (P = .10), and mortality (P = .289). Eight patients (19%) in each treatment group developed reversible renal dysfunction. No AS colistin-related adverse events were recorded.. Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

Topics: Administration, Inhalation; Aged; Anti-Bacterial Agents; Case-Control Studies; Colistin; Female; Gram-Negative Bacterial Infections; Greece; Hospitals, University; Humans; Injections, Intravenous; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Treatment Outcome

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P < or = 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome.

Topics: Administration, Inhalation; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Case-Control Studies; Colistin; Critical Illness; Drug Resistance; Female; Gram-Negative Bacterial Infections; Humans; Immunologic Factors; Male; Middle Aged; Neoplasms; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Retrospective Studies; Severity of Illness Index; Steroids; Treatment Outcome

Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare.. Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series.. Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed.. The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Nosocomial infections by resistant gram-negative microorganisms are important causes of mortality in intensive care unit (ICU)'s. The treatment choices are limited in infections due to Acinetobacter baumannii and Pseudomonas aeruginosa, especially if they are panresistant. In these type of resistant infections, colistin--an old antibiotic--has become a current issue. The aim of this study was to evaluate the efficacy of colistin in 9 cases (6 males, mean age 75.8 +/- 9.4 years), with ventilator associated pneumonia (VAP) caused by panresistant A. baumannii and P. aeruginosa in respiratory ICU. All cases were referred to ICU from other hospitals or clinics. It was detected that 7 of 9 cases were treated with anti-pseudomonal antibiotics before the development of VAP. Panresistant A. baumannii was isolated in 5 cases and P. aeruginosa in 4 cases. VAP by these microorganisms was detected on the 26.6 +/- 12.4th days of invasive mechanical ventilation and the cases were followed up for 54.2 +/- 25.7 days in ICU. During colistin treatment, dermatitis (one case) and nephrotoxicity (one case) were observed as side effects. Microbiological response to colistin was obtained in 6 cases. Three cases died due to non-eradication of panresistant microorganisms and three cases died due to other infections during ICU follow-up. The data presented in this study demonstrates that colistin can be considered as a safe and effective antibiotic in the treatment of panresistant A. baumannii and P. aeruginosa infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections

To determine clinical and microbiologic success in patients receiving adjunctive aerosolized antibiotics for the treatment of ventilator-associated pneumonia (VAP).. Retrospective medical record review.. Level I trauma intensive care unit of a large academic medical center.. Forty-nine patients (mean +/- SD age 42 +/- 19 yrs) who received aerosolized antibiotics for the treatment of a total of 60 episodes of VAP caused by Pseudomonas aeruginosa and/or Acinetobacter baumannii between January 2001 and July 2007.. Patients were identified by using an existing database of patients with documented VAP at the study center. To receive a diagnosis of VAP, patients had to have bacterial growth of 10(5) or more colony-forming units/ml from a bronchoscopic bronchoalveolar lavage and new or changing infiltrate on chest radiograph, plus at least two of the following: abnormal body temperature (> 38 degrees C or < 36 degrees C), abnormal white blood cell count (> 10 or < 4 x 10(3)/mm(3), or > 10% immature bands), or macroscopically purulent sputum. By reviewing patient data, we evaluated clinical and microbiologic success using standard definitions. The median (interquartile range) Injury Severity Score and admission Acute Physiology and Chronic Health Evaluation II score were 40 (29-45) and 17 (9-21), respectively. Pseudomonas aeruginosa, A. baumannii, or both were isolated in 45, 14, and 1 episode(s), respectively. Eighteen VAP episodes included additional bacteria. Aerosolized tobramycin, amikacin, and colistimethate were used in 44, 9, and 9 episodes, respectively. Systemic antibiotics were used in 59 (98%) of the 60 episodes. Clinical success was achieved in 36 (73%) of the 49 first episodes of VAP, 8 (73%) of 11 subsequent episodes, 17 (85%) of 20 episodes that were failing intravenous monotherapy, and 30 (79%) of 38 episodes with multidrug-resistant P. aeruginosa or A. baumannii. Microbiologic success was achieved in 29 (71%) of 41 evaluable episodes. Six patients died from VAP.. Treatment with adjunctive aerosolized antibiotics was associated with a good response rate in critically ill trauma patients with VAP due to nonfermenting gram-negative bacilli. It is noteworthy that episodes of VAP that followed intravenous therapy failure and/or that were due to multidrug-resistant organisms responded well.

Topics: Acinetobacter baumannii; Adult; Aerosols; Amikacin; Anti-Bacterial Agents; APACHE; Colistin; Critical Illness; Drug Resistance, Multiple; Female; Glasgow Coma Scale; Gram-Negative Bacteria; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Tobramycin; Treatment Outcome

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

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

Emergence of multi and pan-drug resistant Gram-negative bacteria causing nosocomial infections in intensive care settings has become a challenge for clinicians. The mortality rate of ventilator-associated pneumonia (VAP) is known to increase when the initial microbiological diagnosis and antimicrobial therapy are inappropriate. We present a case of a 18-year-old man, who after being admitted following an accident, had developed VAP due to multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp. and had a downhill clinical course despite broad-spectrum antibiotic treatment. The strains were found to be Col-S, as the susceptibility was tested. Colistin was instituted, with remarkable recovery. It is imperative to diagnose VAP with multi-drug resistant strains as early as possible; colistin, the 'last resort' antibiotic, if instituted with proper monitoring at the right time, can be life saving.

Topics: Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Treatment Outcome

Tracheotomy is considered to be an independent risk factor for ventilator-associated pneumonia (VAP). Antimicrobial prophylaxis, in particular with coverage of Pseudomonas aeruginosa, is presently advocated. Selective decontamination of the digestive tract (SDD) aims to prevent VAP in critically ill patients, including those after tracheotomy. We determined the incidence and microbial spectrum of VAP after tracheotomy in a SDD-setting.. Retrospective analysis of 231 tracheotomized patients during a 2-year period.. Thirteen patients (5.6%) developed VAP. The median [IQR] day of onset was 8.0 [3.0-10.5] days after tracheotomy. The most predominant causative pathogen was Methicillin-sensitive Staphylococcus aureus (MSSA). Timing of tracheotomy was not different between patients developing VAP and those who did not. The type of tracheotomy (percutaneous or surgical, 84.6% versus 15.4%) had no significant influence on the incidence of VAP.. The incidence of VAP after tracheotomy in a SDD-setting is low, with MSSA as the predominant causative pathogen. Accordingly, if antimicrobial prophylaxis is considered, it may be advisable to cover MSSA in an SDD-setting.

Topics: Administration, Buccal; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Colistin; Critical Illness; Cross Infection; Decontamination; Enteral Nutrition; Female; Gastrointestinal Tract; Humans; Incidence; Intensive Care Units; Male; Methicillin; Microbial Sensitivity Tests; Middle Aged; Netherlands; Pneumonia, Ventilator-Associated; Retrospective Studies; Risk Factors; Staphylococcus aureus; Tobramycin; Tracheotomy

Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens.. To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin.. Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%.. Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies; Treatment Outcome

Our study aimed to determine the efficacy and safety of colistin in the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug-resistant Pseudomonas aeruginosa or Acinetobacter baumanii.. Pairwise, retrospective exposed-unexposed study.. Combined medical and surgical intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia).. Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P. aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa susceptible to imipenem. All patients had normal renal function at the onset of antibiotic therapy.. Case patients were treated by colistin intravenously and control patients were treated by imipenem intravenously.. Baseline characteristics were similar between the colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was 9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20 days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious parameters after the initiation of antibiotic therapy was not statistically different between the two groups. During the antibiotic course, none of the patients in either group developed renal failure.. We conclude that colistin can be a safe and effective option in the treatments of VAP caused by pan-drug-resistant P. aeruginosa or A. baumanii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Injections, Intravenous; Intensive Care Units; Male; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Retrospective Studies; Time Factors

We present our experience with five cases of pandrug-resistant Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) and analysis of risk factors.. Case-control study in a 15-bed intensive care unit (ICU).. The study included 5 cases and 20 controls. Each case patient was matched to four contemporary controls according to gender, prior hospital admissions, hospitalization duration, ICU admission cause, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Function Assessment (SOFA) scores on ICU admission, and length of ICU stay, and mechanical ventilation duration until first VAP episode by a multidrug-resistant bacterium.. Recorded variables included age, gender, daily APACHE II and SOFA scores, patient medication, treatment interventions, positive cultures and corresponding antibiograms, occurrence of infection, sepsis, and septic shock, other ICU-associated morbidity, length of ICU stay and mechanical ventilation, and patient outcome. Healthcare worker and environmental cultures, and a hand-disinfection survey were performed. Pandrug-resistant P. aeruginosa isolates belonged to the same genotype and were bla (VIM-1)-like gene positive. The outbreak resolved following reinforcement of infection-control measures (September 27). The sole independent predictor for pandrug-resistant P. aeruginosa VAP was combined use of carbapenem for more than 20 days and colistin use for and more than 13 days (odds ratio 76.0; 95% confidence interval 3.7-1487.6). An additional risk factor was more than 78 open suctioning procedures during 6-26 September (odds ratio 16.0; 95% confidence interval 1.4-185.4).. Prolonged carbapenem-colistin use predisposes to VAP by pandrug-resistant P. aeruginosa. Cross-transmission may be facilitated by open suctioning.

Topics: Anti-Bacterial Agents; Carbapenems; Case-Control Studies; Colistin; Cross Infection; Disease Outbreaks; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Hand Disinfection; Humans; Intensive Care Units; Logistic Models; Male; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Risk Factors; Suction

Topics: Anti-Bacterial Agents; Bacteria; Colistin; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated

The prospective case series study presented here was conducted to assess the outcome of patients with infections caused by polymyxin-only-susceptible (POS) gram-negative bacteria managed with intravenous colistin. Between July 2003 and April 2005 a total of 27 patients were infected with a POS gram-negative bacterium and received intravenous colistin at a dose of 2 million international units (MIU) (160 mg or 66.7 mg colistin base) every 8 h for a mean (+/-SD) duration of 13.9 (+/-7.5) days. Nine patients had ventilator-associated pneumonia and received, in addition to the intravenous colistin therapy, 1 MIU (80 mg or 33.3 mg colistin base) aerosolized colistin every 12 h for a mean (+/-SD) duration of 13 (+/-6.5) days. The predominant pathogens were Pseudomonas aeruginosa (n = 17) and Acinetobacter baumannii (n = 12); in two patients both pathogens were isolated from one clinical specimen. In-hospital mortality and clinical response were 15% and 85%, respectively. Colistin-associated nephrotoxicity was observed in two of the 27 patients. POS gram-negative pathogens represent a major threat for hospitalized patients. Colistin appears to be an effective and safe treatment, even in patients with severe underlying diseases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Treatment Outcome