Antimicrobal resistance of nosocomial carbapenemase-producing Enterobacterales in Russia: results of surveillance, 2014-2016

Abstract

Objective. To assess the prevalence and antimicrobial susceptibility of carbapenemase-producing Enterobacterales (CPE). Materials and Methods. A total of 5539 Enterobacterales isolates recovered from hospitalized patients in 52 medical institutions in 27 cities in Russia in 2014-2016 were tested. Antibiotic susceptibility testing (AST) was performed using broth microdilution method according to ISO 20776-1:2006. Avibactam was tested in combinations with beta-lactams at fixed concentration of 4 mg/l. AST results were interpreted according to EUCAST v8.1 clinical breakpoints. Carbapenemase production was assessed by carbapenem inactivation method (CIM). Genes for the most common carbapenemases: NDM, VIM, IMP, KPC, and OXA-48, were detected by real-time PCR. Carbapenemase-producing isolates of Klebsiella pneumoniae were subtyped by multilocus sequence typing (MLST). Results. CPE comprised 9.9% of all tested isolates. 7.7% of the isolates were found to produce serinebased carbapenemases of OXA-48 group, 1.9% – metallo-beta-lactamases of NDM group, 0.3% – to co-produce of OXA-48 and NDM. Ceftazidime/avibactam and aztreonam/avibactam demonstrated the highest in vitro activity by inhibited growth of 78.1% (at ≤4 mg/L ceftazidime concentration) and 99.3% (at ≤4 mg/L aztreonam concentration) of the CPE isolates, respectively. Moreover, 94.5% of carbapenemase producers were susceptible to aztreonam/avibactam at ≤0.5 mg/L aztreonam concentration. Among nonbeta-lactam agents, tigecyclin was the most active with 84.8% susceptibility rate. Notably, 11.0% of all CPE were categorized as extensively drug-resistant (XDR). Conclusions. This study shows sharp increase in the prevalence of CPE in Russian hospitals. Carbapenemases of the OXA-48 group were the most prevalent in Enterobacterales followed by NDM. Among all antibiotics tested against CPE isolated from hospitalized patients, combinations of avibactam with ceftazidime and aztreonam were the most active in vitro.

Keywords

• enterobacterales
• carbapenemases
• nosocomial infections
• ceftazidime/avibactam
• aztreonam/avibactam