Indukcja in vitro oporności u Acinetobacter baumannii na sulbaktam i cefoperazon
[In vitro resistance development in Acinetobacter baumannii to sulbactam and cefoperazone]

Streszczenie

Szpitalne szczepy Acinetobacter baumannii są wysoce oporne na wiele grup antybiotyków, czyniąc leczenie infekcji klinicznym wyzwaniem. Celem pra­cy była ocena stopnia indukcji oporności na sulbaktam, cefoperazon oraz cefoperazon w połączeniu z sulbaktamem u Acinetobacter baumannii po zastosowaniu różnych stężeń w zależności od wyjściowych wartości MIC dla tych antybiotyków. Seryjne pasaże w obecności antybiotyków powodowały u większości szczepów trwałe podwyższenie wartości MIC.

Abstract

Introduction. Majority of nosocomial Acinetobacter baumannii strains are highly resistant to many available groups of antibiotics, causing therapy of infections the clinical challenge. The aim of study was to estimate of resistance development to sulbactam, cefoperazone and cefoperazone/sulbactam in Acinetobacter baumannii clinical strains.Methods. Five Acinetobacter baumannii strains (Acb1, Acb2, Acb4, Acb13 and Acb25) were identified by the VITEK 2 GN card and the automatic system VITEK 2 according to the pro­cedure and following the producer`s instructions. Additionaly, the belonging of the strains to the species was confirmed by the presence of the blaOXA-51-like gene. Initial and after antibiotic exposure MIC values of sulbactam, cefoperazone and cefoperazone/sulbactam were determined by using a broth microdilution method. Antibiotic pressure of examined strains was performed in Mueller-Hinton broth containing 0,5x, 0,9x and 2x initial MIC of individual compounds during six-day passages and next six-day passages without antibiotic presence. The Mann-Whitney U test and Kruskal-Wallis non-prarametric Anova test were used to statistical analysis.Results. Serial passaging of Acinetobacter baumannii strains in the presence of antibiotics caused permanent increasing MIC value independently of used concentrations in the majority of examined strains. The highest MIC value increase of sulbactam was found in Acb4 strain. Even after two passages this isolate changed MIC from 0,5 μg/ml to 4 μg/ml (increase about four levels of concentration). Moreover, after incubation in 0,9xMIC concentration similar observation was noted. No normalization of MIC value of sulbactam after incubation during next six passages without sulbactam was observed. In case of cefoperazone the highest levels of induction were noted in Acb1, Acb13 and Acb25 strains. In these strains, after two passages in presence of cefoperazone (2xMIC) the exceedance of minimal of growth concentration over the highest examined concentration was observed. Similar effects were observed in Acb1 strain after stimulation with 0,9x and 0,5xMIC cefoperazone. Return of initial MIC values was received only after induction with 0,5xMIC cefoperazone. In some cases, no opportunities for evaluation of resistance development was noted, because during stimulation with 2xMIC of used antibiotics concentarations, bactericidal effect was found. Conclusions. Sulbactam, cefoperazone and cefoperazone/sulbactam rapidly induce increasing of resistance in Acinetobacter baumannii clinical isolates. Statistically essential MIC increase after using higher concentration than lower was showed. This effect was particularly visible in the case of stimulation of cefoperazone/sulbactam combination.