Activity of ceftolozane-tazobactam against Escherichia coli isolates from u.S. Veterans (2011) in relation to co-resistance and sequence type 131 (ST131) H30 and H30Rx status

Brian D Johnston, Paul Thuras, James R Johnson

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Background Escherichia coli sequence type 131 (ST131), with its multidrug-resistance-associated H30R1 and H30Rx clonal subsets, causes most antimicrobial-resistant E. coli infections in the U.S., especially among veterans. The activity of ceftolozane-tazobactam (C/T), a new beta-lactamase inhibitor agent, against ST131 strains, and E. coli isolates from veterans, is undefined. Methods We determined broth microdilution MICs for C/T and five comparators–piperacillin-tazobac-tam (TZP) levofloxacin (LVX), gentamicin (GEN), ceftazidime (CAZ), and meropenem (MEM)–for 595 clinical E. coli isolates, collected in 2011 from 24 Veterans Affairs Medical Centers across the U.S. Categorical resistance and MICs were compared statistically with resistance category (fluoroquinolone-susceptible, fluoroquinolone-resistant, and extended-spectrum beta-lactamase [ESBL]-producing) and with PCR-defined ST131, H30R1, and H30Rx status. Results Resistance prevalence was 6% for C/T (6%) and MEM (0%), vs. from 8.0% (TZP) to 59% (LVX) for the other comparators. MICs generally increased by resistance category, from fluoroquinolone-susceptible through fluoroquinolone-resistant to ESBL, and by clonal subgroup, from non-ST131-H30 through H30R1 to H30Rx. For each comparator agent except MEM, although a significantly greater fraction of resistant than susceptible isolates were C/ T-resistant, only a minority of comparator-resistant isolates were C/T-resistant (i.e., 9% if LEV-resistant, 12% if GEN-resistant, 21% if CAZ-resistant, 38% if TZP-resistant). Conclusions C/T was broadly active against E. coli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30R1/H30Rx status, outperforming all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing therapy for multidrug-resistant E. coli ST131 infections, including in veterans.

Original languageEnglish (US)
Article numbere0200442
JournalPloS one
Issue number7
StatePublished - Jul 2018

Bibliographical note

Funding Information:
This material is based on work supported by an investigator-initiated grant from Merck and by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grants 1 I01 CX000920-01 and 2I01CX000920-04 (both to JRJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the participating clinical microbiology laboratories for providing clinical isolates.

Publisher Copyright:
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.


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