Ceftolozane/tazobactam plus metronidazole was found to be noninferior to meropenem for the treatment of complicated intra-abdominal infection, according to study findings published in the International Journal of Infectious Diseases.
Patients (N=268) with complicated intra-abdominal infection were enrolled for this study at 21 sites in China between 2019 and 2020. Patients were randomly assigned in a 1:1 fashion to receive either ceftolozane/tazobactam plus metronidazole (group 1) or meropenem plus placebo (group 2) every 8 hours for 4 to 14 days. The primary outcome was to determine whether ceftolozane and tazobactam plus metronidazole is noninferior to meropenem in regard to clinical response rate at the test of cure visit, defined as 26 to 30 days after study initiation.
Among patients in groups 1 (n=134) and 2 (n=134) included in the intention-to-treat (ITT) population, 59.0% and 63.4% were men, the median age was 48.0 (range, 18-75) and 55.0 (range, 18-74) years, creatinine clearance at baseline was 105.1 (range, 50.4-316.0) and 93.0 (range, 42.8-252.3) mL/min, 50.0% and 49.3% had infection of the appendix, and 76.1% and 73.1% previously underwent laparoscopy, respectively.
The most commonly isolated pathogens among patients who adhered to the study protocol and had clinically evaluable outcomes at the test of cure visit were gram-negative aerobes, with Escherichia coli detected in 78 patients, Klebsiella pneumonia in 22, and Pseudomonas aeruginosa in 5.
Clinical cure rates among patients in the ITT population were 85.1% for those in group 1 and 89.6% for those in group 2 (difference, -4.4%; 95% CI, -12.6% to 3.7%). Further analysis was performed after stratification by baseline pathogen. Among patients in groups 1 vs 2, clinical cure rates were 94.0% and 95.0% for those with gram-negative aerobes (difference, -1.0%; 95% CI, -11.9% to 8.7%), 93.8% and 95.7% for those with E coli (difference, -1.9%; 95% CI, -16.5% to 9.4%), 100% and 9.1% for those with K pneumonia (difference, 9.1%; 95% CI, -19.0% to 38.5%), and 80.0% and 88.2% for those with gram-positive aerobes (difference, -8.2%; 95% CI, -42.2% to 20.0%), respectively.
At least 1 adverse event occurred among 67 (50.0%) and 68 (50.7%) patients in groups 1 vs 2, respectively, with cough (5.2% vs 6.7%), diarrhea (6.0% vs 8.2%), and pyrexia (6.7% vs 10.4%) as the most commonly reported events. Further analysis showed that the incidence of drug-related adverse events, including abdominal distension (1.5% vs 0%), abnormal liver function (0% vs 2.2%), diarrhea (1.5% vs 2.2%), nausea (1.5% vs 0.7%), peripheral edema (2.2% vs 1.5%), and rash (0.7% vs 1.5%) were similar between patients in groups 1 vs 2. Of note, 1 death was reported among group 2 patients, and no deaths were reported among those in group 1.
This study may have been limited by basing microbiologic response on clinical response.
According to the researchers, “C/T [ceftolozane and tazobactam] plus metronidazole may provide another option for antibacterial treatment of cIAI [complicated intra-abdominal infection] in China, potentially addressing the need for treatment options for MDR [multidrug-resistant] pathogens.”
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Sun Y, Fan J, Chen G, et al. 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. Int J Infect Dis. 2022;123:157-165. doi:10.1016/j.ijid.2022.08.003