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

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. 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. 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. 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.