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Background β-lactamase-producing Enterobacterales (Eba) frequently carry resistance mechanisms for multiple drug classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Eba, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2017-2020 from patients with urinary tract infections (UTI) as part of the ATLAS global surveillance program. Methods Non-duplicate clinical isolates were collected from 239 sites in 55 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2022 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. Results Based on MIC90 values, ATM-AVI was at least as active as every comparator agent tested against all 15085 Eba isolates collected from UTI (0.12 µg/ml; table), with only five isolates testing with MIC values >8 µg/ml (not shown). Against resistant subsets of isolates, MIC90 values for ATM-AVI were 0.25-0.5 µg/ml, 4- to 8-fold lower than any comparator tested. Against MBL-positive isolates, ATM-AVI MIC values ranged from ≤0.015-2 µg/ml with the exception of one Escherichia coli isolate testing with an MIC value of 16 µg/ml that carried NDM-5, CMY-145, CTX-M-55 and TEM (not shown). Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Eba collected from UTI. Based on the potent in vitro activity of ATM-AVI, continued development of this combination for treatment of UTI caused by drug-resistant Eba is warranted. Disclosures All Authors: No reported disclosures. |
