Abstract

BackgroundCeftazidime–avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases but not class B metallo-β-lactamases (MBLs). Antimicrobial resistance due to these β-lactamases and other mechanisms is increasing and is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Pseudomonas aeruginosa isolates from patients in ICU and non-ICU wards.MethodsNonduplicate clinical isolates were collected in 2016–2017 in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2019 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >2 µg/mL.ResultsThe activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global P. aeruginosa were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI (89% and 92% susceptible, respectively) and for amikacin and colistin. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 72% and 70% of isolates, respectively, of which 18.4% and 18.7% were MBL-positive. CAZ AVI inhibited >83% of MEM-NS MBL-negative isolates globally. In Latin America (LA), CAZ-AVI was active against 87% of isolates from both ward types. Susceptibility rates were generally lower than the global average, especially among MEM-NS isolates and isolates from non-ICU wards. The proportion of MBL-positive isolates in the MEM-NS subset was only slightly higher in LA than globally (19.2% and 19.5% in ICU and non-ICU wards, respectively), suggesting the presence of additional resistance mechanisms. Only colistin exceeded the activity of CAZ-AVI against isolates collected globally and in LA.ConclusionCAZ-AVI showed potent antimicrobial activity, second only to that of colistin, against P. aeruginosa isolates from both ICU and non-ICU wards, with >88% of isolates collected globally testing as susceptible. Activity was in part compromised by MBLs, although additional resistance mechanisms may also be responsible. Disclosures All authors: No reported disclosures.

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