P-1510. <i>In Vitro</i> Activity of Ceftibuten-Avibactam and Comparator Agents Against Enterobacterales Collected Globally as Part of the ATLAS Surveillance Program, 2022 by Region

Abstract Background Ceftibuten is an orally administered third-generation cephalosporin in clinical development in combination with an oral prodrug of avibactam, an inhibitor of class A β-lactamases, including ESBLs and KPC, class C (AmpC) β-lactamases, and some class D (OXA-48) β-lactamases. This study evaluated the in vitro activity of ceftibuten-avibactam and comparators against Enterobacterales isolates collected globally as part of the 2022 Antimicrobial Testing Leadership and Surveillance (ATLAS) program, by region. Methods 23,088 non-duplicate clinical Enterobacterales isolates were collected in 2022 from 217 medical centers in 56 countries. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2024 breakpoints. Ceftibuten was tested with a fixed concentration of 4 µg/mL avibactam. Results Ceftibuten-avibactam was active at ≤1 µg/mL against more isolates than were susceptible to any oral comparator agent (87.3-97.5%). Ceftibuten-avibactam also demonstrated the lowest MIC90 values, by region among the oral agents tested. Regional differences in the in vitro activity of ceftibuten-avibactam were observed with a lower MIC90 value against isolates collected in Europe, North America, the South Pacific, and the Middle East (0.12-0.25 µg/mL) as compared to Latin America, Asia, and Africa (0.5, 4, and 16 µg/mL, respectively). This phenomenon was also observed among oral comparator agents, with fewer isolates collected in Africa susceptible to cefixime (40.8%), cefpodoxime (42.5%), levofloxacin (48.7%), and trimethoprim-sulfamethoxazole (37.8%) than in any other region. A similar pattern was observed for the intravenously administered ceftazidime-avibactam, with 89.3% of isolates collected in Africa susceptible. Conclusion Based on these data, ceftibuten-avibactam demonstrates promise as a candidate for oral treatment of infections caused by Enterobacterales. Regional trends in antimicrobial resistance to a diverse range of agents warrant continued monitoring. Disclosures Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Julie Dickson, BS, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant