Comparison of the In Vitro Susceptibility of Ceftolozane-Tazobactam With the Cumulative Susceptibility Rates of Standard Antibiotic Combinations When Tested Against Pseudomonas aeruginosa From ICU Patients With Bloodstream Infections or Pneumonia.

BACKGROUND

Pseudomonas aeruginosa remains an important cause of hospital-acquired infections in the United States and is frequently multidrug-resistant (MDR). The Infectious Diseases Society of America guidelines recommend empiric combination therapy that includes an antipseudomonal β-lactam with an aminoglycoside or fluoroquinolone likely to cover ≥95% of P. aeruginosa infections in seriously ill patients at risk of having an MDR pathogen. Ceftolozane is an antipseudomonal cephalosporin, combined with the β-lactamase inhibitor tazobactam. Ceftolozane-tazobactam is approved for treatment of complicated urinary tract infections and complicated intra-abdominal infections. A phase 3 clinical trial for the treatment of hospital-acquired pneumonia including ventilator-associated pneumoniae was recently completed. We compared the in vitro susceptibility rate of ceftolozane-tazobactam with the cumulative susceptibility rates of antibiotic combinations commonly used against P. aeruginosa.

METHODS

Isolates were collected from intensive care unit patients hospitalized in 32 US hospitals from 2011 to 2017. The susceptibilities of 1543 P. aeruginosa isolates from bloodstream infections (198 isolates, 12.8%) or pneumonia (1345 isolates, 87.2%) were determined for ceftolozane-tazobactam and comparators.

RESULTS

The most active antimicrobials were colistin (99.4% susceptible), amikacin (98.1% susceptible), and ceftolozane-tazobactam (96.5% susceptible). The susceptibilities to other antipseudomonal β-lactams and fluoroquinolones were <84%. A cumulative susceptibility of ≥95% was reached for cefepime, ceftazidime, meropenem, and piperacillin-tazobactam only in combination with amikacin due to the lower susceptibilities of gentamicin, ciprofloxacin, and levofloxacin. Monotherapies that exceeded 95% were ceftolozane-tazobactam, amikacin, and colistin.

CONCLUSIONS

Ceftolozane-tazobactam monotherapy is likely to be active against more isolates than a combination of another β-lactam and a fluoroquinolone or gentamicin for serious P. aeruginosa infections.