590. Activities of Cefepime-Taniborbactam and Ceftazidime-Avibactam against Cefepime-Resistant Respiratory Gram-Negative Pathogens in a Hollow Fiber Infection Model

Abstract Background Cefepime-taniborbactam (FTB) combines cefepime (FEP), a fourth generation cephalosporin with taniborbactam, novel inhibitor of metallo (MBL)- and serine β-lactamases (SBL). FTB 2.5g IV q8h was safe effective in adults complicated urinary tract infection Phase 3 trial (NCT03840148). is also under development for hospital-acquired ventilator-associated bacterial pneumonia (HABP/VABP). Methods An vitro hollow fiber model (HFM) used to assess resistance emergence MBL- and/or SBL-producing Klebsiella pneumoniae (KP, n=5) Pseudomonas aeruginosa (PA, n=3) treated humanized exposures or ceftazidime-avibactam (CZA). Dense (≥ 7 log10 CFU/mL) log phase cultures were inoculated into HFM cartridges human equivalent doses FEP (2g q8h), (2.5g CZA q8h) 4 days. KP strains collectively harbored NDM (n=2), VIM (n=1), CTX-M (n=4), SHV-ESBL CMY KPC OXA-48 (n=1). PA produced either Pharmacokinetic profiles HFMs, based on free drug plasma healthy volunteers, confirmed by LC-MS/MS. For HFMs MBL-producing strains, EDTA added sequester zinc restore susceptibility (MIC ≤ 8 mg/L). Viable bacteria quantitated serial dilution plating; subpopulations elevated MICs 4x) monitored FTB- CZA-supplemented agar. Results FEP, FTB, ranged 16 > 128 mg/L, 0.5–8 2 respectively. inactive (n=7) bacteriostatic (n=1, MIC=16 bactericidal kill) against all strains; not detected. Against MBL producers, without (n=2) only when disable MBLs. non-MBL which CZA-susceptible, (n=1) allowed growth due Conclusion Humanized high inocula SBL-producing, multidrug-resistant respiratory pathogens prevented The results support HABP/VABP. Disclosures Lindsay M. Avery, PharmD, Venatorx Pharmaceuticals: Employee|Venatorx Stocks/Bonds Mitchell Edwards, n/a, Fan Yi, PhD, Philip E. Sabato, MS, Greg Moeck, Daniel C. Pevear, Stocks/Bonds.