Activity of Ceftolozane-Tazobactam (C/T) against Escherichia coli Isolates from U.S. Veterans in Relation to Co-resistance and Sequence Type 131 (ST131) H30/H30Rx Status

BACKGROUND: E. coli ST131, with its resistance-associated H30 and H30Rx clonal subsets, causes most antimicrobial-resistant E. coli infections, especially among veterans. The activity of the novel combination agent C/T against ST131 is undefined. METHODS: E. coli clinical isolates (n = 595), including (per VAMC) 10 each ciprofloxacin-resistant and susceptible isolates, plus archived ESBL isolates, were collected from 24 VAMCs across the U.S. (2011). ST131, H30, and H30Rx were detected by clonal PCR. Microdilution MICs were determined for C/T and 5 comparators (piperacillin-tazobactam [TZP], levofloxacin [LVX], gentamicin [GEN], ceftazidime [CAZ], and meropenem [MEM]). Categorical resistance and MICs were compared statistically with resistance category and H30/H30Rx status. RESULTS: Total resistance prevalence was < 5% for C/T (3.5%) and MEM (0%), vs. from 7.9% (TZP) to 59% (LVX) for other comparators (Table 1). Resistance prevalence generally increased by resistance category from FQ-S through FQ-R to ESBL, and by clonal subgroup from non-H30 through H30 to H30Rx. CONCLUSION: C/T is broadly active against E. coli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30/H30Rx status; it outperformed all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing agent against multidrug-resistant E. coli ST131 infections. DISCLOSURES: B. D. Johnston, Merck Sharpe & Dohme, Corp.: Collaborator, Research support Actavis: Collaborator, Research support; J. R. Johnson, Merck: Grant Investigator, Research grant Grant Investigator, Research grant