Antimicrobial resistance of nosocomial Enterobacterales isolates in Russia: results of multicenter epidemiological study “MARATHON 2015–2016”

Abstract

Objective. To assess rates of antimicrobial resistance and production of the clinically important acquired resistance mechanisms (extended spectrum beta-lactamases [ESBL] and carbapenemases) in nosocomial strains of Enterobacterales, and to determine genotypes and prevalence of “international high-risk clones” among carbapenemase-producing Klebsiella pneumoniae isolated in various Russian regions within the “MARATHON 2015–2016“ study. Materials and Methods. A total of 2786 non-duplicate nosocomial isolates of Enterobacterales, including 1316 isolates of K. pneumoniae and 837 isolates of Escherichia coli isolated in 49 hospitals from 25 cities in Russia in 2015–2016 were studied. Species identification of isolates was performed using MALDI-TOF mass-spectrometry. Broth microdilution method was used for susceptibility testing and phenotypic ESBL detection. The presence of acquired carbapenemase genes of VIM, IMP, NDM, KPC and OXA-48-groups was determined using real-time PCR. Genotyping of K. pneumoniae isolates was performed by multi-locus sequence typing (MLST) according to the Pasteur institute database and Diancourt et al. method. Results. A total of 48.2% of all bacterial pathogens isolated within the “MARATHON 2015–2016“ study comprised of Enterobacterales. The most common pathogens were K. pneumoniae (47.2%) and E. coli (30.0%). The majority of Enterobacterales isolates were resistant to oxyimino-β-lactam compounds: cefotaxime (78.4%), ceftazidime (67.2%), cefepime (68.4%) and aztreonam (71.5%). ESBL production was determined in 67.8% of isolates. Resistance to carbapenems (imipenem, meropenem and ertapenem) was observed in 6.9%, 6.5% and 23.6% of all Enterobacterales isolates, respectively. A total of 14.4% of Enterobacterales isolates carried the genes of class D carbapenemases OXA-48 (11.4%), class B carbapenemases NDM-1 (2.7%) and class A carbapenemases KPC (< 0.1%). Eight isolates (0.3%) of K. pneumoniae carried the genes of NDM- and OXA-48-like carbapenemases simultaneously and one isolate (< 0.1%) of Proteus mirabilis carried the genes of NDM and VIM metallo-β-lactamases. Most of the 57 genotyped carbapenemase-producing K. pneumoniae isolates belonged to the “international high-risk clones”: CG395 (45.6%), CG11 (12.3%), CG147 (10.5%) and CG307 (10.5%). The most active agents were ceftazidime/avibactam (3.5% of resistant isolates) and aztreonam/avibactam (MIC50 and MIC90 were 0.06 and 0.25 mg/L respectively). Colistin was the most active agent in vitro (18.6% of resistant isolates) among non-β-lactam antibiotics. The only 3.9% of E. coli isolates were resistant to tigecycline. The MIC50/MIC90 values of tigecycline for K. pneumoniae were 0.5 and 2 mg/L and did not exceed ECOFF value (≤ 2 mg/L). Conclusions. The results of this study showed an extremely high prevalence of resistance to most antibiotics, including carbapenems, and a variety of carbapenemase genes in nosocomial isolates of Enterobacterales. It makes a selection of empiric antibiotic treatment extremely difficult and warrants the need for regular resistance surveillance in every hospital.

Keywords

• nosocomial infections
• enterobacterales
• antimicrobial resistance