Characterization of and species complex isolates with decreased susceptibility to cephalosporins from United States hospitals and activity of ceftazidime/avibactam and comparator agents.

Objectives: To evaluate the antimicrobial susceptibility and resistance mechanisms to β-lactams among and from United States medical centres.

Methods: 2571 and 1008 species complex isolates were consecutively collected from 77 medical centres and susceptibility tested by broth microdilution method. Isolates displaying MIC values ≥16 mg/L for ceftazidime or ≥2 mg/L for cefepime (914) were tested for β-lactamase-encoding genes using whole genome sequencing.

Results: Overall susceptibility to ceftazidime and cefepime were 73.9% and 91.2% among and 74.2% and 93.5% among , respectively. Sixty-three isolates harboured a carbapenemase gene, including 56 , 2 , and 5 metallo-β-lactamase genes. Among non-carbapenemase producers, 121 isolates had at least one ESBL-encoding gene, mainly (81) or (61), and 15 had a transferable AmpC gene, mainly (8) or (6). Carbapenemase, ESBL, or transferable AmpC-encoding genes were not identified among 718 of 914 (78.6%) isolates sequenced. The most active agents against isolates with a decreased susceptibility to ceftazidime and/or cefepime were ceftazidime/avibactam (MIC, 0.5/1 mg/L; 99.3% susceptible), amikacin (MIC, 1/4 mg/L; 99.5% susceptible), and meropenem (MIC, 0.06/0.5 mg/L; 92.9% susceptible). The isolates resistant to ceftazidime/avibactam were the five MBL producers and one isolate with a reduced expression of OmpF and overexpression of AcrAB-TolC.

Conclusions: Hyperproduction of chromosomal AmpC appears to be the most common mechanism of resistance to ceftazidime and/or cefepime in and . Ceftazidime/avibactam remained highly active against most isolates showing decreased susceptibility to ceftazidime and/or cefepime.