Abstract
Abstract Background Multidrug-resistant (MDR) Gram-negative bacteria are an increasing worldwide problem. Ceftazidime-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, enzymes that contribute to MDR. This study examined the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods 9193 non-duplicate Enterobacterales (Ent) and 3225 P. aeruginosa (Psa) isolates from were collected from 36 sites in 10 Latin American countries as part of ATLAS 2018-2020. Antimicrobial susceptibility testing was by broth microdilution according to CLSI guidelines and analyzed using CLSI 2022 breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Ent isolates testing with meropenem MICs >1 µg/mL and Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs >1 mg/L were genetically screened for β-lactamases. Psa with meropenem MIC >2 µg/mL were screened in 2018-2019. In 2020, approximately 25% of qualifying Psa were screened. Results The activity of CAZ-AVI and comparators against all isolates and the MDR subsets is shown in the table. CAZ-AVI was active against the full collection of Enterobacterales isolates with 96.7% of the population susceptible and an MIC90 value of 1 µg/mL, and maintained considerable activity against the MDR subset, inhibiting 86.5% of the isolates, a value higher than comparator agents. For the full collection of Psa, 86.6% of the isolates were susceptible to CAZ-AVI, again the highest %S among the comparator drugs. Versus the MDR subset of Psa, CAZ-AVI displayed a 45.8% susceptibility rate, approximately 10% higher than the nearest comparator, amikacin. Conclusion The in vitro data suggest that CAZ-AVI can be an effective therapeutic for infections caused by MDR Enterobacterales in Latin America. MDR among P. aeruginosa remains challenging, although a significant percentage are inhibited by CAZ-AVI. Disclosures All Authors: No reported disclosures.
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