Systematic Review Finds Ceftolozane/Tazobactam Comparable to Standard Therapies for Resistant Gram-Negative Infections

A newly published systematic review synthesizing data from randomized controlled trials reports that ceftolozane/tazobactam demonstrates efficacy comparable to established comparator antibiotics across several serious, drug-resistant infections, including ventilated hospital-acquired and ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, and complicated urinary tract infection .

The review, published in Antibiotics, evaluated comparative efficacy outcomes from two systematic literature reviews that included Phase 2 and Phase 3 randomized trials. The analysis focused on three primary endpoints: all-cause mortality, clinical cure, and microbiological eradication. Trials comparing ceftolozane/tazobactam with meropenem or levofloxacin were included, with particular attention to infections caused by multidrug-resistant Gram-negative pathogens, notably Pseudomonas aeruginosa and Enterobacterales species.

For ventilated hospital-acquired and ventilator-associated bacterial pneumonia, evidence was drawn primarily from the ASPECT-NP Phase 3 trial and related subgroup analyses. Across the overall study population, 28-day all-cause mortality was similar between ceftolozane/tazobactam and meropenem. In several predefined subgroups—such as patients with severe renal impairment, extended-spectrum β-lactamase–producing pathogens, or failure of initial antibacterial therapy—mortality rates were numerically lower with ceftolozane/tazobactam, though the trials were designed to assess non-inferiority rather than superiority. Clinical cure rates and microbiological eradication in these pneumonia populations were also comparable between treatment groups.

In patients with complicated intra-abdominal infection, three randomized trials reported low overall mortality with no statistically significant differences between ceftolozane/tazobactam plus metronidazole and meropenem. Clinical cure rates were similar across treatment arms in all included studies, supporting non-inferiority for this indication.

For complicated urinary tract infection, including pyelonephritis, ceftolozane/tazobactam was compared primarily with levofloxacin in the ASPECT-cUTI trial. Clinical cure rates were similar between groups in the overall population, with non-inferiority demonstrated across analyzed subgroups. Microbiological eradication rates were numerically higher with ceftolozane/tazobactam, with statistically significant differences reported in some analyses, particularly among infections caused by levofloxacin-resistant pathogens.

The authors also assessed risk of bias using the revised Cochrane tool. Most included trials were judged to have low risk of bias across key domains, including randomization, outcome measurement, and reporting. Some smaller studies and subgroup analyses were noted to have limitations related to sample size or exploratory design.

The review emphasizes that many of the included trials were designed as non-inferiority studies and were not powered to detect superiority. In addition, a substantial portion of the data—particularly in high-risk subgroups—was derived from post hoc or subgroup analyses, which should be interpreted cautiously. Safety outcomes were not systematically evaluated in this review.

Overall, the findings indicate that ceftolozane/tazobactam performs similarly to meropenem and levofloxacin across multiple efficacy endpoints in severe Gram-negative infections. The authors note that these results may inform treatment guideline discussions and antimicrobial stewardship strategies, particularly in clinical settings where multidrug-resistant pathogens are suspected or documented.