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Background Cefepime–tazobactam (FEP-TAZ) is in clinical development at 2g/2g q8 hours administered over 90 minutes (high-dose extended infusion). We compared the susceptibility (S) of Gram-negative bacilli (GNB) from patients with bloodstream infections (BSI) and pneumonia (PN) against FEP-TAZ, piperacillin–tazobactam (PIP-TAZ), and ceftolozane–tazobactam (C-T). Methods In 2018, 3,389 GNB isolates (1/patient) were consecutively collected from patients with BSIs (1,349) and PN (2,040) in 40 United States (US) medical centers, and tested by reference broth microdilution methods for S against FEP-TAZ (TAZ at fixed 8 mg/L), PIP-TAZ, C-T, and comparators. The percentage of isolates inhibited at ≤8 mg/L (CLSI, cefepime high dose) and at ≤ 16 mg/L (pharmacokinetic/pharmacodynamic [PK/PD] S breakpoint based on extended infusion and high dosage) of FEP-TAZ were evaluated. Results FEP-TAZ (MIC50/90, 0.06/0.25 mg/L) was the most active TAZ combination against Enterobacterales (ENT) with a spectrum similar to that of meropenem (MEM; 99.3/97.2%S for BSI/PN), ceftazidime–avibactam (CAZ-AVI; 99.8/99.9%S), and amikacin (AMK; 99.3/98.3%S) and retained good activity against ceftriaxone-non-S (CRO-NS) and multidrug-resistant (MDR) ENT (table). Among the β-lactams (BLMs) tested, only FEP-TAZ (57.1/58.6% [BSI/PN] inhibited at ≤ 16 mg/L) and CAZ-AVI (71.4/96.6%S) were active against carbapenem-resistant ENT (CRE). CAZ-AVI (96.7/95.2%S for BSI/PN) and C-T (96.5/94.5%S) were the most active BLMs tested against P. aeruginosa (PSA), followed by FEP-TAZ (95.0/92.1% inhibited a ≤ 16 mg/L), FEP (89.3/78.2%S), and CAZ (85.1/79.0%S). FEP-TAZ (77.8/77.3% inhibited at ≤ 16 mg/L), C-T (81.2/82.9%S), and CAZ-AVI (77.8/84.5%S) retained activity against MEM-NS PSA. FEP-TAZ was the most active BLM against Acinetobacter spp. when the proposed PK/PD breakpoint was applied. Conclusion S rates were markedly lower among isolates from PN compared with BSI. FEP-TAZ was the most active TAZ combination tested against GNB isolated from patients with BSI and PN from US hospitals and exhibited greater spectrum than the carbapenems. The results of this study support further clinical development of high-dose extended-infusion FEP-TAZ for treatment of GNB infections. Disclosures All authors: No reported disclosures.

open forum infectious diseases

2192. Comparative Antimicrobial Susceptibility of Gram-Negative Bacteria Isolated from Patients with Bloodstream Infections and Pneumonia when Tested against Tazobactam Combinations