In vitro activity of ceftazidime–avibactam and comparators against OXA-48-like Enterobacterales collected between 2016 and 2020

ABSTRACT

Oxacillinases (OXA)-48-like β-lactamases are one of the most common resistance determinants among carbapenem-resistant Enterobacterales reported globally. Moreover, there is no standard treatment available against organisms producing OXA-48-like enzymes, and they are sometimes difficult to detect, making treatment challenging. The objective of this study was to evaluate the distribution and antimicrobial susceptibility of bla _OXA-48-like Enterobacterales isolates against ceftazidime–avibactam (CAZ-AVI) and a panel of comparators collected worldwide from 2016 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance program. Among all the Enterobacterales isolates collected, 1.8% (1,690/94,052) carried bla _OXA-48-like, and a majority of those were identified as K. pneumoniae (86.5%, 1,462/1,690). Among all the bla _OXA-48-like isolates, 88.9% (1,502/1,690) were extended-spectrum β-lactamase (ESBL)-positive, 20.7% (350/1,690) were metallo-β-lactamase (MBL)-positive, and 8.9% (150/1,690) were ESBL- and MBL-negative. There were 10 different variants of the OXA-48-like family of enzymes detected, with the major variant being bla _OXA-48 (50.2%, 848/1,690), bla _OXA-232 (29.3%, 496/1,690), and bla _OXA-181 (18.0%, 304/1,690). Overall, all the bla _OXA-48-like isolates showed a susceptibility of 78.6% to CAZ-AVI. Importantly, high susceptibility to CAZ-AVI was shown by all the bla _OXA-48 type, MBL-negative isolates ( n = 1,380, ≥99.0%), and all the MBL-negative isolates ( n = 1,300, ≥97.6%) of the major variants ( bla _OXA-48 , bla _OXA-232, and bla _OXA-181) studied. Among the comparator agents, all isolates showed good susceptibility to only tigecycline (>95.0%) and colistin (>78.6%). Considering the limited treatment options available, CAZ-AVI could be considered as a potential treatment option against bla _OXA-48-like Enterobacterales. However, routine surveillance and appropriate stewardship strategies for these organisms may help identify emerging resistance mechanisms and effective treatment of infections.

IMPORTANCE

Resistance to carbapenems among Enterobacterales is often due to the production of enzymes that are members of the oxacillinases (OXA)-48-like family. These organisms can also be resistant to other classes of drugs and are difficult to identify and treat. This study evaluated the activity of the drug ceftazidime–avibactam (CAZ-AVI) and other comparator agents against a global collection of Enterobacterales that produce OXA-48-like enzymes. CAZ-AVI was active against bla _OXA-48-like Enterobacterales, and only colistin and tigecycline were similarly active among the comparator agents, highlighting the limited treatment options against these organisms. Continued surveillance of the distribution of these OXA 48-like producing Enterobacterales and monitoring of resistance patterns along with the implementation of antimicrobial stewardship measures to guide antibiotic use and appropriate treatment are necessary to avoid drug resistance among these organisms.