Antimicrobial resistance, carbapenemase production, and genotypes of nosocomial Pseudomonas aeruginosa isolates in Russia: results of multicenter epidemiological study “MARATHON 2015–2016”

Objective. Objectives. To assess the rates of antibiotic resistance, production of acquired carbapenemases, genotypes and prevalence of «international high-risk clones» among nosocomial strains of Pseudomonas aeruginosa isolated in various regions of Russia within the «MARATHON 2015–2016» study. Materials and Methods. A total of 1006 non-duplicate nosocomial isolates of P. aeruginosa collected in 44 hospitals from 25 cities in Russia in 2015–2016 were studied. Species identification of isolates was performed by means of MALDI-TOF mass-spectrometry. Antimicrobial susceptibility was determined using broth microdilution method according to ISO 20776-1:2006 and interpreted using EUCAST MIC clinical breakpoints v.9.0. The presence of acquired carbapenemase genes of VIM, IMP, NDM, GES-2 and GES-5 groups was determined using real-time PCR. Genotyping of isolates was performed by analysis of selected single nucleotide polymorphisms in 7 chromosomal loci used for multi-locus sequence typing (MLST) of this species. Results. P. aeruginosa comprised of 17.4% of all bacterial pathogens isolated within the «MARATHON 2015–2016» study. The resistance rates to antibiotics were (in decreasing order of in vitro activity): 1.4% to colistin, 41.5% to aztreonam, 41.6% to ceftazidime/avibactam, 47.7% to amikacin, 51.5% to cefepime, 54.2% to tobramycin, 55.5% to meropenem, 56.3% to gentamicin, 56.8% to ceftazidime, 62.0% to piperacillin/tazobactam, 63.3% to ciprofloxacin, 65.2% to piperacillin, 67.5% to imipenem, and 97,6% to ticarcillin/clavulanic acid. Acquired carbapenemase genes were detected in 35% of the isolates including those for metallo-β-lactamases of VIM- (30.5%) and IMP-type (0.3%) and for GES-5-like serine carbapenemases. MBL producers were highly resistant to all antibiotics except for aztreonam (49%) and polymyxins (0%); GES-5-producers were resistant to most antibiotics except for aztreonam (4.8%), ceftazidime/avibactam (11.9%) and polymyxins (0%). The majority of carbapenemase producing strains belonged to the international “high-risk” CC235 (76.3%) and CC654 (21%) clones. All CC235 isolates revealed the presence of specific variant of the gene encoding secreted phospholipase A2, ExoU, which is a major virulence factor of P. aeruginosa. Conclusions. The results of this study indicate an increase in resistance rates to most antibiotics, including carbapenems, and in prevalence of carbapenemase production in nosocomial strains of P. aeruginosa. This can be largely