In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018

Objectives: This study reports the antimicrobial activity of ceftazidime/avibactam (CZA) and comparators against carbapenemase-producing Enterobacterales (N = 1992) and carbapenemase-producing Pseudomonas aeruginosa (N = 784) collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America (2016-2018). Methods: Minimum inhibitory concentrations (MICs) and susceptibility were determined using broth microdilution methodology and EUCAST breakpoints. Carbapenemase-encoding genes were detected using multiplex PCR. Results: No isolates of carbapenemase-producing, metallo-beta-lactamase (MBL)-negative Enterobacterales from Africa/Middle East or Latin America were resistant to CZA; resistance rates in Europe and Asia/South Pacific were <= 4.5%. Colistin had the lowest resistance rate among MBL-positive isolates (6.0-11.4%). Enterobacterales isolates collected in Latin America predominantly carried a KPC carbapenemase (77.6%), whereas in Africa/Middle East OXA-48-like carbapenemases were most frequently detected (55.9%), and in Asia/South Pacific most isolates carried NDM carbapenemases (56.2%). Among all Enterobacterales carrying KPC carbapenemases, the lowest rate of resistance was to CZA (1.5%), and among isolates carrying NDM carbapenemases it was to colistin (10.8%). Among carbapenemase-producing, MBL-negative P. aeruginosa, resistance rates to CZA were 8.6% for isolates collected in Europe and 53.2% in Latin America. Isolates in each region most frequently carried VIM carbapenemases, ranging from 41.7% of isolates in Asia/South Pacific to 86.2% in Africa/Middle East. No P. aeruginosa carrying KPC or NDM carbapenemases and 1.0% of isolates carrying GES carbapenemases were resistant to colistin. Conclusion: Given the limited therapeutic options to treat infections caused by carbapenemase-positive Enterobacterales and P. aeruginosa, continued surveillance of CZA activity as well as agents such as colistin is crucial. (C) 2021 Pfizer and The Author(s). Published by Elsevier Ltd. on behalf of International Society for Chemotherapy of Infection and Cancer

Automated summary

In Africa/Middle East and Latin America, carbapenemase-producing Enterobacterales without MBL were not resistant to CZA; resistance rates were <= 4.5% in Europe and Asia/South Pacific. Enterobacterales in Latin America predominantly carried KPC carbapenemase, while in Africa/Middle East OXA-48-like carbapenemases were most frequently detected, and in Asia/South Pacific most isolates carried NDM carbapenemases.