Efficacy, safety, and tolerability of antimicrobial agents for complicated intra- abdominal infection: a systematic review and network meta-analysis

Abstract

Background Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted. Methods We systematically searched 4 major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAIs treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration’s risk of bias tool as described in Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of interests. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAI. Results Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAI were included in network meta-analyses. The vast majority of patients with an APACHE II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cephalosporin-based regimens were more effective and better tolerated than tigecycline with regard to clinical success rate (odds ratio [OR] = 1.3, 95% confidence interval [CI] 1.00 ~ 1.70) and discontinuation due to adverse events (OR = 0.69, 95% CI 0.44 ~ 1.00). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates and all-cause mortality. A statistically significant trend was observed favoring carbapenems, which exhibited fewer discontinuations because of adverse events when compared with tigecycline (OR = 0.66, 95% CI 0.42 ~ 1.00). In pairwise meta-analyses, compared with tigecycline, carbapenems (2,315 participants, OR = 1.32, 95% CI 1.00 ~ 1.75, I2 = 24.0%) were associated with superior clinical success rate. These results were of borderline statistical significance. Compared with tigecycline, carbapenems (2,304 participants, OR = 0.67, 95% CI 0.45 ~ 0.91; I2 = 48.5%) were associated with significantly reduced risk of serious adverse events. According to the surface under the cumulative ranking curve analysis, cephalosporin-based regimens were more likely to be optimal among all treatments in terms of efficacy, and tigecycline was more likely to be worst regimen in terms of safety and tolerability. Conclusion This study suggests that cephalosporin-based regimens are optimal for the empiric treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering safety and tolerability concerns. However, it should be noted that data currently available for antimicrobial agent’ effectiveness, safety, and tolerability pertain mostly to lower-risk patients with cIAIs.