Novel beta-lactam/beta-lactamase inhibitors plus metronidazole versus carbapenem for complicated intra-abdominal infections: a meta-analysis of randomized controlled trials
Abstract 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 the randomized controlled trials (RCTs) was performed using databases of 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 2,254 patients were included. The meta-analysis showed that novel BL/BLIs in combination with metronidazole had a lower clinical success rate (RD, -0.05; 95%CI, [-0.07, -0.02]; I2= 0%), and lower microbiological success rate (RD, -0.04; 95%CI, [-0.08, -0.00]; I2= 0%). No difference was found between two groups in the incidence of AEs (RD, 0.02; 95%CI, [-0.01, 0.06]; I2= 0%), serious adverse events (SAEs) (RD, 0.01; 95%CI, [-0.02, 0.03]; I2= 0%) and mortality (RD, 0.01; 95%CI, [-0.00, 0.02]). However, ceftazidime/avibactam had a higher risk of vomiting (RD, 0.03; 95% CI, [0.01, 0.05]; I2= 47%), and ceftolozane/tazobactam subgroup showed a higher incidence of SAEs (RD, 0.12; 95% CI, [0.01, 0.03]). Conclusions The efficacy of novel BL/BLIs in combination with metronidazole was not as good as carbapenems. Although no significant differences were found with respect to overall AEs, SAEs and mortality, the novel BL/BLIs has a higher risk of vomiting. Clinical application of new anti-infective combination still needs to be cautious. Trial registration PROSPERO ID: 42020166061