In Vitro Activity of Ceftazidime-avibactam and Comparators Against Gram-negative Bacterial Isolates Collected in the Asia-Pacific Region As Part of the INFORM Program (2015-2017)

Background: Antimicrobial resistance among nosocomial Gram-negative pathogens is a cause for concern in the Asia-Pacific region. The aims of this study were to measure the rates of resistance among clinical isolates collected in Asia-Pacific countries, and to determine the in vitro antimicrobial activities of ceftazidime-avibactam and comparators against these isolates.

Methods: CLSI broth microdilution methodology was used to determine antimicrobial activity and EUCAST breakpoints version 9.0 were used to determine rates of susceptibility and resistance. Isolates were also screened for the genes encoding extended-spectrum β-lactamases (ESBLs) or carbapenemases (including metallo-β-lactamases [MBLs]).

Results: Between 2015 and 2017, this study collected a total of 7051 Enterobacterales isolates and 2032 Pseudomonas aeruginosa isolates from hospitalized patients in Australia, Japan, South Korea, Malaysia, the Philippines, Taiwan, and Thailand. In the Asia-Pacific region, Enterobacterales isolates that were ESBL-positive, carbapenemase-negative (17.9%) were more frequently identified than isolates that were carbapenemase-positive, MBL-negative (0.7%) or carbapenemase-positive, MBL-positive (1.7%). Multidrug-resistant (MDR) isolates of P. aeruginosa were more commonly identified (23.4%) than isolates that were ESBL-positive, carbapenemase-negative (0.4%), or carbapenemase-positive, MBL-negative (0.3%), or carbapenemase-positive, MBL-positive (3.7%). More than 90% of all Enterobacterales isolates, including the ESBL-positive, carbapenemase-negative subset and the carbapenemase-positive, MBL-negative subset, were susceptible to amikacin and ceftazidime-avibactam. Among the carbapenemase-positive, MBL-positive subset of Enterobacterales, susceptibility to the majority of agents was reduced, with the exception of colistin (93.4%). Tigecycline was active against all resistant subsets of the Enterobacterales (MIC, 1-4 mg/L) and among Escherichia coli isolates, > 90% from each resistant subset were susceptible to tigecycline. More than 99% of all P. aeruginosa isolates, including MDR isolates and the carbapenemase-positive, MBL-positive subset, were susceptible to colistin.

Conclusions: In this study, amikacin, ceftazidime-avibactam, colistin and tigecycline appear to be potential treatment options for infections caused by Gram-negative pathogens in the Asia-Pacific region.