1081. Antimicrobial Activity of Ceftibuten-Avibactam against Clinical Isolates of <i>Enterobacterales</i> Producing Clinically Relevant Beta-Lactamases

Abstract Background Ceftibuten (CTB) is an oral cephalosporin active against Enterobacterales approved by the US Food and Drug Administration in 1995. Avibactam (AVI) a potent inhibitor of extended-spectrum β-lactamases (ESBLs), serine carbapenemases AmpC that can be administered orally. We evaluated vitro activity CTB-AVI molecularly characterized produced most common (BLs) assessed AVI concentration to combined with CTB for susceptibility testing. Methods The organism collection (n=71) included producing ESBLs (28; CTX-M, SHV, TEM), KPCs (8), MBLs (7; NDM, VIM, IMP), derepressed (3), plasmid OXA-48-like (2), SME (2) as well isolates porin alterations (5) wild-type organisms (13). Resistance mechanisms were whole genome sequencing. MIC values determined broth microdilution fixed concentrations (2, 4, 8 mg/L) ratios (1:1 2:1) AVI. Results 4 mg/L best separated CTB-AVI-susceptible from CTB-AVI-resistant isolates. (fixed was very ESBL (MIC50/90, 0.03/0.12 mg/L), including CTX-M-15 KPC (MIC50, 0.06 (MIC range, 1-2 plasmidic 0.12-0.5 0.06-0.12 0.5-4 but it showed limited MBL-producers &amp;gt;128 32 mg/L; Table). SME-producers (MIC, 0.12-0.25 some KPC-producers 2-16 ESBL-producers 4/64 exhibited MBL, derepressed, AmpC, producers (MIC50 128 mg/L). Conclusion clinically relevant BLs, ESBLs, KPCs, OXA-48-like, which treatment options are available. These results support further clinical development CTB-AVI. Disclosures Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. Support)Cipla Therapeutics USA Inc. Support)Department Health Human Services Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC Support)Nabriva Support)Pfizer, Support)Shionogi Support)Spero Support) Jill Lindley, Bravos Biosciences Support)ContraFect Corporation Support)Qpex Biopharma Lalitagauri M. Deshpande, Timothy B. Doyle, Support)Bravos Support)GlaxoSmithKline Support)Melinta Mariana Castanheira, Support)Cidara Affinity Biosensors (Individual(s) Involved: Self): Research Support; Allergan Amicrobe, Inc Amplyx Pharma Artugen USA, Astellas Basilea Beth Israel Deaconess Medical Center BIDMC bioMerieux BioVersys Ag Bugworks Cidara Cipla Contrafect Cormedix Crestone, Curza CXC7 Entasis Fedora Pharmaceutical Fimbrion Fox Chase GlaxoSmithKline Guardian Hardy Diagnostics IHMA Janssen &amp; Development Johnson Kaleido Biosceinces KBP Luminex Matrivax Mayo Clinic Medpace Meiji Seika Co., Melinta Menarini Merck Meridian Bioscience Micromyx MicuRx N8 Nabriva National Institutes University Singapore North Bristol NHS Trust Novome Biotechnologies Paratek Pfizer Prokaryotics QPEX Rhode Island Hospital RIHML Roche Roivant Salvat Scynexis SeLux Shionogi Specific Spero SuperTrans LT T2 Biosystems Queensland Thermo Fisher Scientific Tufts Universite de Sherbrooke Iowa Hospitals Clinics Wisconsin UNT System College Pharmacy URMC UT Southwestern VenatoRx Viosera Wayne State Support