Novel Combination Ceftolozane/tazobactam Shows Promise Against P. aeruginosa and Enterobacteriaceae Isolates

SAN DIEGO, CA—Ceftolozane/tazobactam has greater in vitro activity than ceftazidime, cefepime, and piperacillin/tazobactam when tested against P. aeruginosa and Enterobacteriaceae strains that cause pneumonia in U.S. hospitals, as seen in a study presented at IDWeek 2012.

Ceftolozane is a novel oxyimino-aminothiazolyl cephalosporin with very potent activity against P. aeruginosa.  The combination of ceftolozane/tazobactam is currently under clinical development for treatment of ventilator-associated bacterial pneumonia, complicated intra-abdominal infections, and urinary tract infections.

A total of 1,089 clinically significant, consecutively collected, non-duplicate isolates of gram-negative bacilli were utilized from patients with pneumonia in 32 U.S. medical centers in the year 2011. The samples were analyzed for susceptibility with Clinical Laboratory Standards Institute broth microdilution processes.

Helio Sader, MD, PhD, from JMI Laboratories, North Liberty, IA reported that ceftolozane/tazobactam was the most active β-lactam tested against P. aeruginosa, inhibiting 97.6% and 94.2% of strains at ≤8µg/mL and ≤4µg/mL, respectively. Ceftolozane/tazobactam (MIC50/90, 1/4µg/mL) was 2- to ≥8-fold more active than ceftazadime (MIC50/90, 2/32µg/mL) or cefepime (MIC50/90,4/>16µg/mL). P. aeruginosa exhibited low susceptibility to ceftazidime (79.5%), cefepime (79.5%), piperacillin/tazobactam (72.6%) and meropenem (74%).

Ceftolozane/tazobactam exhibited activity against P. aeruginosa strains non-susceptible to ceftazidime (MIC50/90, 4/16µg/mL; 88.3% inhibited at ≤8µg/mL), to meropenem (MIC50/90, 1/8µg/mL; 90.8% inhibited at ≤8µg/mL), and to both ceftazidime and meropenem (57 strains; MIC50/90, 4/32µg/mL; 78.9% inhibited at ≤8µg/mL).

Against non-extended spectrum beta lactamase-pheontype Klebsiella species, ceftolozane/tazobactam (MIC50/90, 0.25/0.5µg/mL) activity was similar to that of ceftazidime (MIC50/90, 0.12/0.5µg/mL). Extended spectrum beta lactamase-phenotype strains showed lower susceptibility to all β-lactams, including meropenem (MIC90, >8µg/mL; 66% susceptible), as well as ciprofloxacin (MIC90, >4µg/mL; 27.7% susceptible) and gentamicin (MIC90, >8µg/mL; 48.9% susceptible).

Against Enterobacter species, ceftolozane/tazobactam (MIC50/90, 0.5/8µg/mL; 90.8% inhibited at ≤8µg/mL) was slightly more potent than ceftazidime (MIC50/90, 0.25/>32µg/mL; 73.3% susceptible), ceftriaxone (MIC50/90, 0.25/>8µg/mL; 69.5% susceptible) and piperacillin/tazobactam (MIC50/90, 4/64µg/mL; 80.2% susceptible).