Comparing novel antibiotics and carbapenems for complicated intra-abdominal infections: a systematic review and meta-analysis of randomized controlled trials

Abstract

Carbapenem-sparing antibiotic is urgently needed for patients with complicated intra-abdominal infections (cIAIs). Even though several novel antibiotics - novel β-lactam-β-lactamase inhibitor combinations - ceftolozane-tazobactam and ceftazidime-avibactam, and novel tetracycline derivative - eravacycline have been developed for cIAIs, whether these antibiotics are comparable to carbapenem for cIAIs remain unclear. A comprehensive search was conducted on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov until October 1, 2022. Only RCTs that compared the clinical efficacy and safety of novel antibiotic against carbapenem for patients with cIAIs were included. Among 11 selected RCTs, no significant differences were observed in terms of clinical cure rate at test of cure between the study and the control group in the analysis of clinical evaluable population (93.6% vs 93.7%, risk ratio [RR], 1.00; 95% CI, 0.98-1.01; p = 0.84), microbiologically evaluable population (93.0% vs 94.5%; RR, 0.98; 95% CI, 0.96-1.00; p = 0.10), and modified intention-to-treat population (85.9% vs 87.7%; RR, 0.98; 95% CI, 0.95-1.01; p = 0.13). All these findings remain consistent across the subgroup analyses and sensitivity tests. Similarly, there were no significant differences in terms of microbiological eradication between the study and the control group (87.8% vs 89.7%; RR, 0.98; 95% CI, 0.96-1.01; p = 0.18). The risks of adverse events were similar between groups. The clinical efficacy, microbiological response, and safety of the novel antibiotics, including ceftazidime-avibactam, ceftolozane-tazobactam, and eravacycline are comparable to carbapenem in the treatment of patients with cIAI. These agents can be potential therapeutic options as carbapenem-sparing antibiotic for cIAIs.