Novel beta-lactam/beta-lactamase inhibitors plus metronidazole versus carbapenem for complicated intra-abdominal infections: a meta-analysis of randomized controlled trials

Background Complicated intra-abdominal infections (cIAIs) remain a leading cause of death in surgical wards, in which antibiotic treatment is crucial. We aimed to compare the efficacy and safety of novel β-lactam/β-lactamase inhibitors (BL/BLIs) in combination with metronidazole and carbapenems in the treatment of cIAIs. Methods A comprehensive search of randomized controlled trials (RCTs) was performed using Medline, Embase, and Cochrane Library, which compared the efficacy and safety of novel BL/BLIs and carbapenems for the treatment of cIAIs. Results Six RCTs consisting of 2254 patients were included. The meta-analysis showed that novel BL/BLIs in combination with metronidazole had a lower clinical success rate (risk difference [RD], -0.05; 95% CI, -0.07 to -0.02; I2 = 0%) and a lower microbiological success rate (RD, -0.04; 95% CI, -0.08 to -0.00; I2 = 0%). No difference was found between the 2 groups in incidence of adverse events (RD, 0.02; 95% CI, -0.01 to 0.06; I2 = 0%), serious adverse events (SAEs; RD, 0.01; 95% CI, -0.02 to 0.03; I2 = 0%), or mortality (RD, 0.01; 95% CI, -0.00 to 0.02). However, ceftazidime/avibactam had a higher risk of vomiting (RD, 0.03; 95% CI, 0.01 to 0.05; I2 = 47%), and the ceftolozane/tazobactam subgroup showed a higher incidence of SAEs (RD, 0.12; 95% CI, 0.01 to 0.03). Conclusions The efficacy of novel BL/BLIs in combination with metronidazole was not as high as that of carbapenems. Although no significant differences were found with respect to overall adverse events, SAEs, or mortality, the novel BL/BLIs has a higher risk of vomiting. We still need to be cautious about the clinical application of a new anti-infective combination. Trial registration PROSPERO ID: 42020166061.