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

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. We determined broth microdilution MICs for C/T and five comparators-piperacillin-tazobactam (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. 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). 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.