Pooled data from phase 3 clinical trials comparing the clinical activity of ceftolozane/tazobactam versus meropenem for the treatment of complicated intra-abdominal infections.

Abstract

Background: Ceftolozane/tazobactam (C/T) in combination with metronidazole is an active antimicrobial therapy used to treat complicated intra-abdominal infections (cIAIs).

Methods: A comparison of the clinical efficacy of C/T plus metronidazole vs. meropenem for the treatment of cIAIs using pooled data from four phase 3 clinical studies (CXA-cIAI-10-08, CXA-cIAI-10-09, NCT02739997 and NCT03830333).

Results: In total, 1,361 patients (C/T plus metronidazole, n = 721; meropenem, n = 640) were included in the pooled analysis. Clinical response rates at the test of cure (TOC) visit in the intention-to-treat (ITT) and clinically evaluable populations were 84.3% (608/721) and 86.9% (556/640) as well as 93.4% (534/572) and 93.8% (483/515), and at the end of treatment visits the rates were 90.6% (653/721) and 91.9% (588/640) as well as 96.5% (552/572) and 96.6% (499/515) for C/T plus metronidazole and meropenem, respectively. Microbiological response rates at the TOC visits in the modified ITT population were 85.3% (440/516) and 89.3% (442/495), and in the extended microbiological evaluable population 93.7% (399/426) and 94.3% (394/418) for C/T plus metronidazole and meropenem, respectively. Adverse events occurred in 341/716 (47.6%) and 280/631 (44.4%) patients treated with C/T plus metronidazole and meropenem, respectively. The most common adverse events across treatment groups were diarrhoea, nausea, pyrexia and insomnia. No new serious safety findings were identified.

Conclusions: The efficacy of C/T plus metronidazole was comparable with meropenem even for cIAIs and C/T plus metronidazole might be an alternative treatment option for cIAI.