Ceftolozane-tazobactam (Zerbaxa®) is a combination of a novel cephalosporin (CXA-101) with the beta-lactamase inhibitor tazobactam. A marketing authorisation application for the treatment of complicated urinary tract infections and complicated intra-abdominal infections was accepted by the EMA in August 2014 but it has not yet been approved for use in the EU.
This trial evaluated the efficacy and safety of ceftolozane/tazobactam in patients with mostly community-acquired complicated intra-abdominal infections. A related Comment notes that the patient population was high risk: one-fifth were aged ≥65 years, one-third had renal impairment, >80% had peritonitis, and the most frequent site of infection was the appendix. Although the microbiology of infecting pathogens was similar to that observed in other phase 3 studies in this indication, the overall rate of infection with ESBL-positive isolates (7.2%) was higher than in previous observations.
The primary endpoint of this study was the clinical cure rate 24-32 days after the initiation of therapy (the test of cure visit). The primary analysis was conducted in the microbiological intent-to-treat population, with a non-inferiority margin of 10%. The analysis conducted for the EMA however looked at the clinically evaluable population, with a non-inferiority margin of 12.5%. Non-inferiority of ceftolozane-tazobactam + metronidazole to meropenem was demonstrated for both of these populations. Cure rates were also high in the small patient subgroups with ESBL-producing Enterobacteriaceae (95.8% v 88.5%) and CTX-M-14/15 ESBLs (100% v 72.7%).
The results of the study suggest that ceftolozane/tazobactam plus metronidazole may offer a new treatment option for complicated intra-abdominal infections, especially when multi-drug resistant organisms (e.g. resistant Enterobacteriaceae) are suspected.