Ceftolozane/tazobactam with metronidazole effective against complicated intra-abdominal infections

USA: A new study published in the International Journal of Infectious Diseases showed that, in Chinese patients with complicated intra-abdominal infection (cIAI), ceftolozane/tazobactam (C/T) with metronidazole was noninferior to meropenem for clinical response.

Antibiotic resistance is a major clinical and financial burden that poses a danger to public health on a worldwide scale. Current treatment choices for some bacterial infections are restricted for patients with cIAI due to antibacterial resistance, which raises mortality and emphasizes the need for alternative treatment options. Data on the use of C/T with metronidazole in Chinese patients are currently few. The effectiveness and safety of C/T with metronidazole vs. meropenem for the treatment of cIAI in adult volunteers of Chinese ethnicity are thus reported by Yihong Sun and colleagues.

Chinese adult participants with cIAI were randomized 1:1 to receive ceftolozane/tazobactam plus metronidazole or meropenem plus placebo in this phase 3 clinical research. The main goal was to compare the clinical response rate of ceftolozane/tazobactam with metronidazole to that of meropenem at the test of cure visit in the clinically evaluable (CE) group. Clinical and microbiologic responses at the test of cure (TOC) and end of treatment (EOT; 24 hours after the last dose) visits, as well as adverse event rates, were considered secondary end goals.

The key findings of this study were:

1. For ceftolozane/tazobactam with metronidazole and meropenem, respectively, the clinical cure at the TOC visit in the CE population was 95.2% and 93.1%; hence, noninferiority was satisfied.

2. Microbiologic responses at the TOC visit and clinical responses at the TOC and EOT visits were in line with the main efficacy end objective.

3. In terms of safety, research treatment groups were equivalent.

In conclusion, within this cohort, the safety profile of C/T with metronidazole was good and consistent with both meropenem and the findings of the global pivotal study. When combined, C/T and metronidazole may provide patients with another antibacterial therapy alternative, thereby meeting the demand for MDR pathogen treatment choices.

Reference:

Sun, Y., Fan, J., Chen, G., Chen, X., Du, X., Wang, Y., Wang, H., Sun, F., Johnson, M. G., Bensaci, M., Huntington, J. A., & Bruno, C. J. (2022). A Phase 3, Multicenter, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem in Chinese Participants With Complicated Intra-abdominal Infections. In International Journal of Infectious Diseases. Elsevier BV. https://doi.org/10.1016/j.ijid.2022.08.003