Antimicrobial activity of plazomicin against Enterobacteriaceae-producing carbapenemases from 50 Brazilian medical centers

Abstract

Plazomicin is a next-generation aminoglycoside with activity against Enterobacteriaceae, including carbapenemase-producing Enterobacteriaceae (CPE). The aim of this study was to evaluate the activity of plazomicin against CPE (Klebsiella spp., Escherichia coli, Serratia spp., Enterobacter spp., Citrobacter spp., Morganella spp., Proteus spp., Providencia spp.) from different Brazilian hospitals. A total of 4000 carbapenem-resistant Enterobacteriaceae isolates were collected from clinical samples in 50 Brazilian hospitals during 2013–2015. Of these, 499 carbapenem-resistant isolates (CLSI criteria) were selected for further evaluation via broth microdilution to assess for the activity of plazomicin, colistin, tigecycline, meropenem, amikacin, and gentamicin. Additionally, the isolates were assessed for the presence of carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like, blaIMP, blaBKC, blaGES, and blaVIM) by polymerase chain reaction (PCR). When PCR was positive to blaOXA-48-like, blaIMP, blaGES, and blaVIM, the carbapenemase genes were sequenced. blaKPC was the most prevalent carbapenemase gene found (n=397), followed by blaNDM (n=81), blaOXA-48 (n=12), and blaIMP-1 (n=3). Other genes were identified in only 1 isolate each: blaBKC-1, blaGES-16, blaGES-1, blaOXA-370, and blaVIM-1. One isolate had 2 carbapenemase genes (blaKPC and blaNDM). Thirty-three percent of the isolates were nonsusceptible to colistin, 24% to tigecycline, 97% to meropenem, 51% to amikacin, and 81% to gentamicin (via EUCAST criteria). The plazomicin MIC50/90 was 0.5/64mg/L, with 85% of MICs ≤2mg/L and 87% of MICs ≤4mg/L. Elevated MICs to plazomicin were not associated with a specific carbapenemase or bacterial species. The MICs of plazomicin against CPE were lower than those of other aminoglycosides. Plazomicin is a promising drug for the treatment of CPE infections.