1436. Comparison of Ceftazidime–Avibactam, Ceftolozane–Tazobactam, Piperacillin–Tazobactam, and Meropenem Activities When Tested Against Gram-Negative Organisms Isolated From Complicated Urinary Tract Infections

Abstract

BackgroundComplicated urinary tract infections (cUTIs) represent a major cause of healthcare-associated infection and a major source of gram-negative (GN) bacteremia. We evaluated the antimicrobial activities of recently approved β-lactamase inhibitor combinations and comparators against GN bacteria isolated from patients with cUTIs in the US hospitals in 2018.MethodsUnique patient isolates were consecutively collected from patients with cUTIs in 65 hospitals in 2018, and the GN organisms (n = 4,371) were susceptibility (S) tested by reference broth microdilution methods. Enterobacterales (ENT) with elevated cephalosporin MICs were screened for β-lactamase-encoding genes by whole-genome sequencing.ResultsThe most common GN organisms were E. coli (44.5%), K. pneumoniae (19.6%), P. mirabilis (6.7%), and P. aeruginosa (PSA; 5.3%). The most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.7%S), and meropenem (MEM; 99.4%S; table). Extended-spectrum β-lactamase (ESBL) genes were identified in 315 ENT (7.6%; excluding carbapenemase co-producers), including CTX-M-15 (63% of ESBL producers), other CTX-M types (25%), OXA-1/OXA-30 (39%), and SHV type (30%); approximately 50% of ESBL producers had ≥2 ESBL genes, mainly a CTX-M-type and an OXA-type (37% of isolates). The most active agents against ESBL producers were CAZ-AVI (100.0%S), AMK (99.7%S), and MEM (99.4%S); whereas ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) were active against 90.6% and 84.8% of ESBL producers, respectively. Only CAZ-AVI (87.0%S), colistin (COL; 87.0%S), and tigecycline (95.7%S) exhibited good activity against carbapenem-resistant ENT (CRE). Only 3 ENT isolates (0.07%) were CAZ-AVI resistant and all had a metallo-β-lactamase gene (2 VIM-1 and 1 NDM-1). CAZ-AVI (97.0%S) and C-T (99.1%S) were the most active β-lactams tested against PSA; other compounds with > 90%S for PSA were COL (99.6%), AMK (97.8%), tobramycin (93.5%), and CAZ (90.4%).ConclusionCAZ-AVI was highly active against a large collection of contemporary GN bacteria isolated from patients with cUTIs in US hospitals and provided greater coverage than the agents currently available in the US to treat cUTIs. Disclosures All authors: No reported disclosures.