An in vitro comparison of ceftolozane/tazobactam compared to traditional beta-lactams as an alternative to combination antimicrobial therapy for Pseudomonas aeruginosa [PublishAheadOfPrint]

Background: Guidelines for sepsis, febrile neutropenia, and hospital-acquired pneumonia include empiric regimens incorporating two antibiotics from different classes with activity against Pseudomonas aeruginosa for select at-risk patients to increase the likelihood of susceptibility to at least one agent.

Objectives: The activity and cross-resistance rates of ceftolozane/tazobactam were compared to β-lactam comparators cefepime, ceftazidime, piperacillin/tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin against P. aeruginosa.

Methods: Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods.

Results: Of the 1257 isolates collected, 29% were from the ICU, and 39% were from respiratory sites. Overall susceptibility to ceftolozane/tazobactam was high at 97%, compared to 72-76% for cefepime, ceftazidime, piperacillin/tazobactam, and meropenem. Non-susceptibility to all four comparator β-lactams was 11%; of these, 80% remained susceptible to ceftolozane/tazobactam. Among the isolates non-susceptible to the tested β-lactam comparator, fewer than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the β-lactam non-susceptible isolates were susceptible to tobramycin, for overall cumulative susceptibilities of 94-95%, nearly 10% higher than that of the ciprofloxacin/β-lactam combinations and approaching that of ceftolozane/tazobactam as a single agent.

Conclusions: Ceftolozane/tazobactam susceptibilities were consistently high, with little observable cross-resistance. Ceftolozane/tazobactam monotherapy performed at or above the level of commonly utilized combination therapies based on in vitro susceptibilities. Ceftolozane/tazobactam should be considered for patients at high risk for resistant P. aeruginosa infection and as an alternative to empiric combination therapy, especially for patients unable to tolerate aminoglycosides.

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