P-1509. <i>In Vitro</i> Activity of Aztreonam-Avibactam Against Enterobacterales Isolated from Pediatric and Adult Patients Collected During the ATLAS Global Surveillance Program, 2018-2022

Abstract Background The spread of antimicrobial resistance among clinically isolated Enterobacterales (Eba) is a threat to public health. Aztreonam (ATM) is a monobactam stable against hydrolysis by metallo-β-lactamases (MBLs) and avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases. ATM-AVI is being developed for use against infections caused by drug-resistant Eba, especially those co-producing MBLs and other β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2018-2022 from pediatric and adult patients as part of the ATLAS global surveillance program. Methods 87621 Eba isolates were collected from patients in 226 medical centers in 57 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. PCR and sequencing were used to identify β-lactamase genes among all isolates testing with meropenem MIC &amp;gt;1 µg/mL, and a randomly sampled subset of approximately 80% of Escherichia coli, Klebsiella spp. and Proteus mirabilis testing with ATM or ceftazidime MIC &amp;gt;1 µg/mL. Results MIC90 values for ATM-AVI of 0.12 µg/mL (pediatric isolates) and 0.25 µg/mL (adult isolates) were observed. Against all Eba isolates, ≤8 µg/mL of ATM-AVI inhibited 99.9% of both pediatric and adult isolates, whereas only 66.3% (pediatric) and 71.4% (adult) of these isolates were susceptible to ATM alone (table). Among isolates that screened positive for an MBL, MIC90 values for ATM-AVI were 0.5 µg/mL (pediatric) and 2 µg/mL (adult) and ATM-AVI inhibited 100% (pediatric) and 98.6% (adult) at concentrations ≤8 µg/ml. In contrast, only 14.5% (pediatric) and 17.2% (adult) of MBL-positive isolates were susceptible to ATM without AVI. Conclusion Based on MIC90 values, ATM-AVI demonstrated potent in vitro activity against Eba isolated both from pediatric and adult patients. Avibactam’s ability to potentiate aztreonam against MBL-positive Enterobacterales isolates warrants its continued development. Disclosures Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Julie Dickson, BS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant