Фенотипові і генотипові детермінанти антибіотикорезистентності грамнегативних бактерій – етіологічних чинників інфекційних ускладнень бойових ран

Abstract

For the present day, antibiotic-resistant gram-negative bacterial flora dominates among the pathogens of infectious complications of war wounds. In the process of choosing and predicting the effectiveness of therapeutic measures, the data related to the phenotypic evidence of antibiotic resistance, as well as its genetic determinants are of vital importance. Genetic analysis data will help determine the mechanisms by which the resistance to antibiotics is implemented, establish genes that are inactive, but potentially can compromise the effectiveness of antibiotics. The information on the distribution of antibiotic-resistant genes will determine the tendency of the epidemic situation changing in the system of medical evacuation and assistance to the wounded, as well as develop the anti-epidemic measures. The purpose of the study was to determine antibiotic resistance phenotypes and antibiotic resistance genes peculiar to gram-negative bacteria, which inflict the infectious complications of war wounds in a modern military conflict in Ukraine. Methods. Antibiotic susceptibility testing of eighteen gram negative bacteria isolates which caused infectious complications of battle wounds had been studied automatically on the three commercial platforms according to current Clinical and Laboratory Standards Institute guidelines. The isolates underwent analysis by whole genome sequencing with “next – generation sequencing” method on applied biosystems/life technologies platform. Comparison of identified genome sequences had been done with Genbank data using Basic Local Alignment Search Tool technology. Results. Overall, 47 different antibiotic resistance genes were identified among the presented isolates. Acinetobacteria sp. isolates carried beta-lactamases of the classes blaTEM-1B and blaOXA-2, blaOXA-24, blaPER-1. Studied Klebsiella sp., Enterobacteriaceae sp. and P. aeruginosa harbor several narrow-spectrum β-lactamases. The blaCTX-M-15 gene encoding the extended spectrum of beta-lactamase was detected in K. pneumoniae and in all isolates of E. cloacae. A. baumanii, E. cloacae and K. pneumoniae were capable to produce carbapenemases. In Acinetobacteria sp., this phenotype was associated with the blaOXA-23 and blaOXA-24 genes, for Enterobacteriaceae sp. – with blaOXA-48. Conclusions. The investigated microorganism strains express multidrug-resistant phenotypes. The genome of these strains contains the genes determining the resistance to carbapenems, aminoglycosides, low effectiveness of fluoroquinolones and unprotected cephalosporins, which explains the associated resistance to antibiotics with different mechanisms of antimicrobial activity. It is reasonable to use the obtained data in the process of developing the practical recommendations for the rational use of antibiotics in the treatment of infectious complications of war wounds.