In vitro susceptibility of carbapenem resistant Enterobacterales to meropenem-vaborbactam and ceftazidime-avibactam at a single academic medical centre

• Published in: Infectious diseases (London, England) Vol. 55; no. 4; pp. 282 - 291
• Main Authors: Adams, Jenna, Santarossa, Maressa, Harrington, Amanda, Bauer, Michael, Wozniak, Amy, Labuszewski, Laurie, Albarillo, Fritzie S.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.04.2023
• Subjects: Academic Medical Centers; Anti-Bacterial Agents - pharmacology; antibiotic susceptibility; beta-Lactamases; Carbapenems; ceftazidime-avibactam; Drug Combinations; Humans; Klebsiella pneumoniae; Meropenem - pharmacology; Meropenem-vaborbactam; Microbial Sensitivity Tests; minimum inhibitory concentration; Retrospective Studies; Meropenem-vaborbactam; antibiotic susceptibility; ceftazidime-avibactam; minimum inhibitory concentration
• ISSN: 2374-4235; 2374-4243; 2374-4243
• DOI: 10.1080/23744235.2023.2177337

Carbapenem-resistant Enterobacterales (CRE) are considered an urgent threat. Ceftazidime-avibactam and meropenem-vaborbactam contain β-lactamase inhibitors active against CRE isolates including those that produce Klebsiella pneumoniae carbapenemases (KPC). Retrospective chart review of CRE isolates from 1 January 2016 to 1 November 2018. Collected data includes a descriptive overview of measured MIC values, resistance mechanism via a polymerase chain reaction test (Xpert Carba-R, Cepheid, Sunnyvale CA), as well as clinical outcomes. Of 106 isolates reviewed, 86 isolates met the inclusion criteria from 85 individual subjects. The breakpoint:MIC ratio for ceftazidime-avibactam overall was 4, while for meropenem-vaborbactam this ratio was 32 (p < 0.0001). For KPC isolates, ceftazidime-avibactam MIC 50 /MIC 90 in 2016, 2017, and 2018 were 2/4 mg/L (n = 32), 2/4 mg/L (n = 17), and 2/8 mg/L (n = 30), respectively. The meropenem-vaborbactam MIC 50 /MIC 90 , for KPC isolates in 2016, 2017, and 2018 were 0.06/0.125 mg/L (n = 32), 0.06/0.1 mg/L (n = 17), and 0.06/0.5 mg/L (n = 30), respectively. Microbiologic cure was 75% (n = 16) in ceftazidime-avibactam subjects and 58.3% (n = 12) in subjects treated with alternative agents (p = 0.43). The 14- and 30-day mortality was numerically higher in subjects treated with alternate agents when compared ceftazidime-avibactam 2/9 (22.2%) vs 3/17 (17.6%) (p = 1.00) and 4/9 (44.4%) vs 4/17 (28.6%) (p = 0.38), respectively. For ceftazidime-avibactam, 30-day mortality in 2016, 2017, and 2018 was 0/5 (0%), 0/2 (0%), and 4/10 (40%). Selective pressure from the use of ceftazidime-avibactam at our institution may be decreasing its utility as a first-line agent for CRE infections. Meropenem-vaborbactam maintained low MIC values and may be a promising treatment option for CRE.