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

Abstract

Background: Carbapenem-sparing antibiotics are needed urgently for patients with complicated intra-abdominal infections (cIAIs). Although several novel antibiotics - novel β-lactam/β-lactamase inhibitor combinations (e.g. ceftolozane-tazobactam and ceftazidime-avibactam) and a novel tetracycline derivative (eravacycline) - have been developed for cIAIs, it remains unclear whether these antibiotics are comparable to carbapenems for the treatment of cIAIs.

Methods: A comprehensive search of PubMed, Embase, Cochrane Library and ClinicalTrials.gov was conducted until 1 October 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacy and safety of novel antibiotics against carbapenems for patients with cIAIs were included.

Results: Among the 11 selected RCTs, no significant differences in clinical cure rate at the test-of-cure visit were observed between the study group and the control group on analysis of the clinically evaluable population [93.6% vs 93.7%, risk ratio (RR) 1.00, 95% confidence interval (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 findings were consistent across the subgroup analyses and sensitivity tests. Similarly, no significant difference in microbiological eradication was observed between the study group and the control group (87.8% vs 89.7%, RR 0.98, 95% CI 0.96-1.01; P=0.18). The risk of adverse events was similar in both groups.

Conclusions: Clinical efficacy, microbiological response and safety of the novel antibiotics, including ceftazidime-avibactam, ceftolozane-tazobactam and eravacycline, are comparable to carbapenems for the treatment of patients with cIAIs. These agents can be potential therapeutic options as carbapenem-sparing antibiotics for cIAIs.

Keywords: Carbapenems; Ceftazidime-avibactam; Ceftolozane-tazobactam; Complicated intra-abdominal infection; Eravacycline.