Antimicrobial Susceptibility of KPC-Producing Enterobacteriaceae Stratified by Infection Site (US, 2012–2015)

Abstract

Background. KPC-producing strains have been increasingly reported worldwide and these isolates, predominantly K. pneumoniae (KPN), are often resistant to most or all available antimicrobials. We evaluated the antimicrobial susceptibility of KPCproducing Enterobacteriaceae isolates from various infection types. Methods. Four hundred sixty-five KPC-producing Enterobacteriaceae clinical isolates were collected from 49 USA medical centers in 2012-2015 as part of the INFORM Surveillance Program, and tested for susceptibility by reference broth microdilution methods using ceftazidime-avibactam (CAZ-AVI; AVI at fixed 4 μg/mL), gentamicin (GEN), amikacin (AMK), tigecycline (TIG), colistin (COL) and others. CLSI, US-FDA (CAZ-AVI and TIG), and EUCAST (COL) interpretative criteria were applied. KPC and other β-lactamase genes were detected by PCR/sequencing. Results. KPN represented 83.9% of the collection, and Enterobacter spp. was the second most common organism (n = 31; 6.7%). The most active agents overall were CAZ-AVI (99.4% susceptible [S]) and TIG (98.9% S; Table). Only 81.5% and 59.4% of isolates were S to COL and AMK, respectively. Only 3 isolates were CAZ-AVInon-S, and 2 of them co-produced a metallo-β-lactamase (NDM-1 or VIM-4). KPC-producing isolates were more commonly isolated from pneumonia (n = 153), urinary tract (UTI; n = 99) and skin/soft-tissue infections (SSSI; n = 74). CAZ-AVI (98.0%-100.0% S) and TIG (94.1%-100.0% S) were consistently active against isolates from all sites of infections, whereas S rates varied from 77.8% to 92.8% for COL, 51.5% to 64.7% for AMK and 43.2% to 60.4% for GEN. Levofloxacin was active against only 15.7% of isolates. Among KPN, S rates were 99.2% for CAZ-AVI and only 80.5% for COL. S rates for CAZ-AVI among isolates from intensive care unit (ICU) patients did not vary substantially compared to those from non-ICU patients. Conclusion. The novel β-lactam/β-lactamase inhibitor combination CAZ-AVI was very active against this large collection of KPC-producing isolates (99.4% S) and represents a very valuable addition to the limited armamentarium currently available for the treatment of infections caused by KPC-producing Enterobacteriaceae. (Table Presented) .