In vitro activity of biapenem and other carbapenems against Russian clinical isolates of Pseudomonas aeruginosa, Acinetobacter spp., and Enterobacterales

Objective. To evaluate in vitro activity of biapenem and other clinically available carbapenems against Russian clinical isolates of Enterobacterales, Pseudomonas aeruginosa и Acinetobacter spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams. Materials and Methods. A total of 3139 Enterobacterales isolates, 793 P. aeruginosa isolates and 634 Acinetobacter spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net). Results. For all tested Escherichia coli isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.125⁄0.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial E. coli isolates had MIC >4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of Klebsiella pneumoniae for biapenem were 0.5⁄16 mg/l, for both imipenem and meropenem – 0.5⁄32 mg/l, for ertapenem – 2⁄32 mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against Enterobacterales isolates. For 321 carbapenemase-producing K. pneumoniae isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired P. aeruginosa isolates were 8⁄64 mg/l and 0,5⁄16 mg/l for biapenem, 8⁄128 mg/l and 1⁄16 mg/l – for imipenem, 16⁄64 mg/l and 0,5⁄32 mg/l – for meropenem. All carbapenems, including biapenem, had very low in vitro activity against carbapenemaseproducing P. aeruginosa isolates. МПК50/90 of Acinetobacter spp. were 64⁄128 mg/l for biapenem, 64⁄128 mg/l – for imipenem, and 128⁄128 mg/l – for meropenem. Conclusions. According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, in vitro activity of biapenem against Russian clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. was comparable to those of imipenem and meropenem.