1445. Antimicrobial Activity of Novel β-Lactamase Inhibitor Combinations Tested against Organisms Causing Complicated Urinary Tract Infections in United States Medical Centers

Abstract

BackgroundHigh-dose extended-infusion cefepime-tazobactam (FEP-TAZ) is in clinical development at 2g/2g q8 hours administered over 90 minutes. We evaluated the potency and spectrum of activity of FEP-TAZ, ceftolozane–tazobactam (C-T), ceftazidime–avibactam (CAZ-AVI), and comparators tested against gram-negative bacilli (GNB) causing complicated urinary tract infections (cUTIs) in United States (US) hospitals.MethodsIn 2018, 3,023 GNBisolates (1/patient) were consecutively collected and susceptibility tested against FEP-TAZ (TAZ at fixed 8 mg/L) and comparators by reference broth microdilution methods. Percentage of isolates inhibited at ≤8 mg/L (CLSI, cefepime high dose) and at ≤16 mg/L (pharmacokinetic/pharmacodynamic [PK/PD] susceptible [S] breakpoint based on extended infusion and high dosage) were evaluated.ResultsFEP-TAZ (99.9% inhibited at ≤16 mg/L; Table), CAZ-AVI (99.9%S), and meropenem (MEM; 99.5%S) were the most active agents against Enterobacterales (ENT). An ESBL phenotype (CLSI criteria) was observed in 12.5%, 12.9%, and 3.6% of E. coli (EC), K. pneumoniae (KPN), and P. mirabilis (PM), respectively. FEP-TAZ and CAZ-AVI exhibited complete activity against EC, whereas C-T and piperacillin–tazobactam (PIP-TAZ) were active against 91.5% and 88.1% of ESBL-phenotype EC isolates, respectively. The most active agents against KPN were FEP-TAZ (99.6% inhibited at ≤16 mg/L), CAZ-AVI (100.0%S), and amikacin (AMK; 99.4%S). All PM isolates were S to FEP-TAZ (highest MIC, 0.12 mg/L), C-T, CAZ-AVI, MEM, PIP-TAZ and AMK. FEP-TAZ was highly active against E. cloacae (n = 94; MIC90, 0.5 mg/L; 98.9% inhibited at ≤16 mg/L) and Citrobacter spp. (n = 91; MIC90, 0.12 mg/L; highest MIC, 0.5 mg/L). Against P. aeruginosa (PSA), FEP-TAZ inhibited 97.6% of isolates at ≤16 mg/L, with spectrum of activity similar to CAZ-AVI (96.4%S), C-T (99.4%S) and AMK (97.6%S), and greater than MEM (85.5%S) and PIP-TAZ (87.3%S).ConclusionFEP-TAZ showed potent activity against ENT and PSA isolated in US hospitals in 2018, with overall spectrum (ENT + PSA) similar to CAZ-AVI and greater than C-T, PIP-TAZ, and MEM when FEP-TAZ proposed PK/PD S breakpoint of ≤16 mg/L was applied. FEP-TAZ may represent a valuable option for treating cUTIs caused by resistant GNB. Disclosures All authors: No reported disclosures.