ABSTRACT
The emergence of Acinetobacter baumannii with resistance to colistin (ABRC) led to the investigation of daptomycin as an adjunctive to colistin for these isolates. In this study, one ABRC carbapenemase-producing bloodstream isolate was examined. Minimum inhibitory concentrations (MICs) were >512, >512 and 8 µg/mL for imipenem, daptomycin and colistin, respectively. First, a 'humanised' model of the pharmacokinetics of daptomycin and colistin was developed in 18 male C57BL/6 mice. Then, 112 mice were infected by intraperitoneal injection of the ABRC isolate and were randomly assigned into four groups of once-daily treatment for 7 days: group A, controls treated with saline; group B, treated with 20 mg/kg colistin; group C, treated with 50 mg/kg daptomycin; and group D, treated with both agents. Survival was recorded for 7 days in ten mice per group. The remaining mice were sacrificed at regular time intervals following bacterial challenge and the bacterial outgrowth in the liver, lung and right kidney was determined. Mean serum concentrations of daptomycin at 15, 30 and 60 min post-dose were 121.8, 110.3 and 100.4 µg/mL, respectively. The respective concentrations of colistin were 13.9, 9.1 and 7.5 µg/mL. The 7-day mortality in groups A, B, C and D was 100%, 50%, 100% and 0%, respectively. Tissue outgrowth of the right kidney was significantly decreased in group D compared with group B after 72 h. Daptomycin used in combination with colistin leads to prolonged survival in an experimental infection by ABRC. Failure of colistin alone is probably related to rebound of tissue outgrowth.
Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/therapeutic use , Colistin/therapeutic use , Daptomycin/therapeutic use , Acinetobacter baumannii/isolation & purification , Animals , Anti-Bacterial Agents/blood , Bacterial Proteins/metabolism , Daptomycin/blood , Disease Models, Animal , Drug Resistance, Multiple, Bacterial , Drug Synergism , Drug Therapy, Combination , Humans , Imipenem/pharmacology , Male , Mice , Mice, Inbred C57BL , Microbial Sensitivity Tests , beta-Lactamases/metabolismABSTRACT
Trimethoprim-sulfamethoxazole alone and combined with colistin was tested in vitro against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical strains. After 24 h, at achievable serum concentrations, trimethoprim-sulfamethoxazole effectively killed all strains, while colistin killed only one strain. Trimethoprim-sulfamethoxazole plus colistin rapidly killed all strains after 6 h and for up to 24 h. Trimethoprim-sulfamethoxazole, one of the few remaining antimicrobials that still has a degree of activity, particularly combined with colistin, might represent an effective therapy for severe CRAB infections.
Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Colistin/pharmacology , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Acinetobacter baumannii/genetics , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Humans , Microbial Sensitivity TestsABSTRACT
hyplex®-MBL ID Multiplex PCR-ELISA, a novel method for identifying metallo-ß-lactamase genes directly in clinical specimens, was evaluated using a consecutive collection of 326 samples from three hospitals in Greece characterized by high prevalence of VIM producers. The method exhibited high sensitivity (98.0%) and specificity (98.6%) and was proven reliable in detecting bla(VIM) genes in blood, urine, pus, and sputum samples that, as confirmed by conventional methods, contained various VIM-producing species. Future multicenter studies should be considered for the thorough evaluation of this method and its potential diagnostic utility.
Subject(s)
Bacterial Proteins/genetics , Gram-Negative Bacteria/enzymology , Gram-Negative Bacterial Infections/microbiology , Polymerase Chain Reaction/methods , beta-Lactamases/genetics , Bacterial Proteins/biosynthesis , Enzyme-Linked Immunosorbent Assay/methods , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/isolation & purification , Greece , Humans , Microbial Sensitivity Tests/methods , Sensitivity and Specificity , beta-Lactamases/biosynthesisABSTRACT
We investigated a multidrug-resistant Acinetobacter baumannii outbreak in the Intensive Care Unit (ICU) of a tertiary care hospital in Greece over a 3-month period. Molecular typing of the outbreak isolates from 31 patients revealed that two distinct genotypes were involved. Nine isolates, belonging to both genotypes, were resistant to carbapenems. Samples from the ICU environment and from the hands of personnel were collected to identify possible contamination. Class 1 integrons of 3.1, 2.5 and 2.2 kb were amplified from the clinical and environmental isolates. The 3.1 kb integron carrying five gene cassettes was found for the first time in A. baumannii. The outbreak ceased after implementation of hygienic measures in the ICU, including complete cleaning and disinfection.
