Geographic variations in distributions of carbapenemase-encoding genes, susceptibilities, and minimum inhibitory concentrations of inpatient meropenem-resistant Enterobacterales to ceftazidime-avibactam, meropenem-vaborbactam, and aztreonam-avibactam across four global regions: 2020-2022 data from the Antimicrobial Testing Leadership and Surveillance.
Journal
International Journal of Antimicrobial Agents
Journal Volume
66
Journal Issue
1
Start Page
Article Number : 107500
ISSN
1872-7913
Date Issued
2025-07
Author(s)
Abstract
Purpose: To evaluate the susceptibility profiles of regional inpatient meropenem-resistant (MEM-R) carbapenemase-producing Enterobacterales (CPE) isolates and their MIC values to ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB), and aztreonam-avibactam (ATM-AVI) Methods: The 2020–2022 Antimicrobial Testing Leadership and Surveillance database were analyzed. Carbapenemase-encoding genes in CPE isolates were identified using multiplex PCR and Sanger sequencing. Susceptibility breakpoints for CZA and MVB recommended by CLSI 2024 and EUCAST 2025 against Enterobacterales were applied. Results: A total of 2,318 CPE isolates (78.2% were Klebsiella pneumoniae) were tested globally. Notable diversity in carbapenemase-encoding gene distributions was observed among CPE isolates from Africa/the Middle East (10 countries; n=361), Asia (7 countries, excluding India and Pakistan; n=182), Europe (17 countries; n=1,002), and Latin America (10 countries; n=773). Metallo-β-lactamase-encoding genes, predominantly blaNDM-1, were more frequently detected in CPE isolates from Africa/the Middle East (75.3%, except blaNDM-5 in Kuwait) and Asia (67%, except blaIMP-8 in Taiwan) compared to other regions. Among KPC variants, the KPC-2 enzyme was the predominant one in CPE isolates in Europe (43.4%, except for KPC-3 prevalent specifically in Italy) and in Latin America (62.1%). The susceptibility rates of all analyzed CPE isolates harboring only a single blaKPC gene to CZA and MVB were 99.4% and 93.5%, respectively, based on the CLSI 2024 susceptibility breakpoints. The MIC50/90 values of CPE isolates to ATM-AVI were 0.12/0.25 mg/L and 0.5/1 mg/L, respectively, regardless of collection region, dual carbapenemase production, or infection source. Conclusions: The trends in resistance to novel antibiotics among contemporary CPE isolates need close monitoring.
Subjects
Antimicrobial Testing Leadership and Surveillance
Aztreonam-avibactam
Carbapenemase-producing Enterobacterales
Ceftazidime-avibactam
Meropenem-vaborbactam
Susceptibility rates
Publisher
Elsevier B.V.
Type
journal article