Ceftolozane/Tazobactam Activity Tested Against Bacterial Bloodstream Isolates from Multiple Infection Sources

Background: Ceftolozane/tazobactam (C/T) is approved by the US-FDA for the treatment of intra-abdominal infections and complicated urinary tract infections, including pyelonephritis. We evaluated the activity of C/T and comparators against Enterobacteriaceae (ENT) and Pseudomonas aeruginosa (PSA) bloodstream infection (BSI) isolates stratified by infection source (where known).

Methods: 12,204 ENT and 1,541 PSA BSI clinical isolates collected worldwide (from North America, Europe and Asia-Western Pacific) from 2011–2015 were susceptibility (S) tested by reference broth microdilution methods against C/T (TAZ at fixed 4 µg/mL) and comparators.  CLSI breakpoints were applied for C/T (ENT, ≤2 µg/mL; PSA, ≤4 µg/mL) and comparator compounds.

Results: C/T inhibited 93.2% of all ENT and 90.7% of all PSA BSI isolates at the CLSI breakpoints (Table).  Against PSA BSI isolates derived from various identified infection sites, C/T S ranged from 80.8% [skin and skin structure infection (SSSI)] to 93.7% (urinary tract infection; UTI), and C/T activity was markedly superior to meropenem (MEM) overall (90.7 vs. 75.6% S for all PSA isolates) and against each of the isolate subsets.  C/T was also very active against ENT isolates derived from multiple sites of infection [%S range, 84.3 (lower respiratory tract; LRT) to 95.6% (UTI)].  The only two infection sites for which ENT isolates exhibited S <90% were intravenous/IV line (88.2% S) and LRT (84.3% S), and these constituted only 9.7% of all ENT isolates. Notably, C/T was more active than piperacillin/tazobactam (P/T) against the overall ENT isolate set (93.2% vs. 88.7% S) and against the isolate subsets from each site of infection. 

Conclusion: C/T was active against a large worldwide collection of ENT (93.2% S, CLSI) and PSA (90.7% S, CLSI) BSI isolates collected 2011-2015, regardless of infection source.  Among the antimicrobials tested here, C/T was the most active β-lactam against PSA and, except for the carbapenems, was also the most active β-lactam against ENT. C/T may represent a valuable treatment option for BSI caused by Gram-negative pathogens.