Ceftolozane/Tazobactam Plus Metronidazole: Effective Treatment for Intra-Abdominal Infection

CHINA: In accordance with results published in the International Journal of Infectious Diseases, ceftolozane/tazobactam plus metronidazole was reported to be noninferior to meropenem for the treatment of complex intra-abdominal infection.

Antibiotic resistance is a major clinical and financial burden that poses a threat to public health on a worldwide scale. Current therapeutic choices for some bacterial pathogens in patients with complex intra-abdominal infection (cIAI) are constrained due to antibiotic resistance, which raises mortality and emphasizes the need for alternative therapeutic options. Data on the application of C/T with metronidazole in Chinese patients are currently few.

Therefore, the authors sought to compare meropenem and C/T with metronidazole for the treatment of cIAI in adult participants of Chinese descent to ascertain their effectiveness and safety.

Between 2019 and 2020, patients (N=268) with difficult intra-abdominal infection were enrolled for this trial at 21 locations in China. Ceftolozane/tazobactam plus metronidazole (group 1) or meropenem plus placebo (group 2) were given to patients at random in a 1:1 ratio every eight hours for 4 to 14 days. The main goal was to ascertain if the combination of ceftolozane, tazobactam, and metronidazole is noninferior to meropenem in terms of the clinical response rate at the test of cure visit, which was 26 to 30 days after the study started.

Key findings of the study:

• Escherichia coli was found in 78 patients, Klebsiella pneumonia in 22, and Pseudomonas aeruginosa in 5, making gram-negative aerobes the most frequently identified pathogens in patients who followed the study protocol.
• Clinical cure rates were 85.1% for group 1 and 89.6% for group 2 in the ITT population (difference, -4.4%; 95% CI, -12.6% to 3.7%).
• In comparison between groups 1 & 2, the clinical cure rates were 94.0% and 95.0% for gram-negative aerobes (difference, -1.0%; 95% CI, -11.9% to 8.7%), 93.8% and 95.7% for E coli (different, -1.9%; 95% CI, -16.5% to 9.4%), 100% and 9.1% for K pneumonia (difference, 9.1%; 95% CI, -19.0% to 38.5%), and 80.0% and 88.2% for gram-positive aerobes (difference, -8.2%; 95% CI, -42.2% to 20.0%), respectively.
• Subjects in groups 1 and 2 experienced similar rates of drug-related side effects, such as 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%).
• one death noted in Group 2 and none in group 1.

In China, "ceftolozane and tazobactam plus metronidazole may provide another alternative for antibacterial therapy of complicated intra-abdominal infection, potentially addressing the demand for treatment choices for multidrug-resistant infections," the researchers concluded.

REFERENCE

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