Prevalence of carbapenemase genes among carbapenem-nonsusceptible collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents.

OBJECTIVES

To evaluate the prevalence of acquired β-lactamase genes and susceptibility profiles of carbapenem-nonsusceptible (CNSE) clinical isolates collected in US hospitals during a 5-year period.

METHODS

Isolates were susceptibility tested by reference broth microdilution methods. Results were interpreted using CLSI breakpoints. Isolates displaying nonsusceptible MICs for imipenem or meropenem were categorized as CNSE. CNSE isolates were screened for β-lactamase-encoding genes using whole-genome sequencing. New genes were cloned, expressed in an background and susceptibility tested.

RESULTS

A total of 450 (1.3%) isolates were CNSE. serine carbapenemase (KPC) production was the most common resistance mechanism among CNSE isolates: 281/450 (62.4%) carried , including three new variants. OXA-48-like and metallo-β-lactamase (MBL) encoding genes were detected among seven and 12 isolates, respectively. Among MBL genes, was the most common, but , and were also identified. 169 (37.6% of the CNSE) isolates did not produce carbapenemases. Ceftazidime/avibactam was the most active agent (95.0% to 100.0% susceptible) against CNSE isolates from all carbapenemase groups except MBL-producing isolates. Ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam inhibited 100.0%, 97.6% and 92.3% of the non-carbapenemase CNSE isolates, respectively. Among the three new variants, one conferred resistance to ceftazidime/avibactam and low meropenem MIC results while the other two had profiles similar to or .

CONCLUSIONS

A decline in carbapenemase production was noticed in US hospitals in the 5-year period analysed in this study. New β-lactam/β-lactamase inhibitor combinations tested had good activity against CNSE isolates.