PMID- 37085768 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20230425 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 23 IP - 1 DP - 2023 Apr 21 TI - Efficacy, safety, and tolerability of antimicrobial agents for complicated intra-abdominal infection: a systematic review and network meta-analysis. PG - 256 LID - 10.1186/s12879-023-08209-9 [doi] LID - 256 AB - 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 four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs. RESULTS: Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated. CONCLUSION: This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs. CI - (c) 2023. The Author(s). FAU - Kong, Wenqiang AU - Kong W AD - Department of Pharmacy, Zi Gong First People's Hospital, Zi Gong, China. FAU - Deng, Ting AU - Deng T AD - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Shiqin AU - Li S AD - Department of Pharmacy, Zi Gong First People's Hospital, Zi Gong, China. FAU - Shu, Yunfeng AU - Shu Y AD - Department of Pharmacy, Zi Gong First People's Hospital, Zi Gong, China. FAU - Wu, Yanyan AU - Wu Y AD - Department of Pharmacy, Women and Children's Hospital of Chongqing Medical University, Chongqing, China. 271206049@qq.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230421 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 37A4IES95Q (ceftolozane) RN - 07896928ZC (eravacycline) RN - 140QMO216E (Metronidazole) RN - FV9J3JU8B1 (Meropenem) RN - 70JE2N95KR (Tigecycline) RN - 807PW4VQE3 (Cefepime) RN - 0 (Anti-Bacterial Agents) RN - 0 (ceftolozane, tazobactam drug combination) RN - SE10G96M8W (Tazobactam) RN - 0 (Anti-Infective Agents) SB - IM MH - Adult MH - Humans MH - Metronidazole/adverse effects MH - Meropenem/therapeutic use MH - Network Meta-Analysis MH - Tigecycline/therapeutic use MH - Cefepime/therapeutic use MH - Anti-Bacterial Agents/adverse effects MH - *Intraabdominal Infections/drug therapy/microbiology MH - Tazobactam/therapeutic use MH - *Anti-Infective Agents/adverse effects PMC - PMC10122415 OTO - NOTNLM OT - Antimicrobial agents OT - Complicated intra-abdominal infection OT - Efficacy OT - Network meta-analysis OT - Safety OT - Systematic review OT - Tolerability COIS- The authors declare that they have no competing interests. EDAT- 2023/04/22 10:42 MHDA- 2023/04/25 06:42 PMCR- 2023/04/21 CRDT- 2023/04/21 23:32 PHST- 2022/12/31 00:00 [received] PHST- 2023/03/30 00:00 [accepted] PHST- 2023/04/25 06:42 [medline] PHST- 2023/04/22 10:42 [pubmed] PHST- 2023/04/21 23:32 [entrez] PHST- 2023/04/21 00:00 [pmc-release] AID - 10.1186/s12879-023-08209-9 [pii] AID - 8209 [pii] AID - 10.1186/s12879-023-08209-9 [doi] PST - epublish SO - BMC Infect Dis. 2023 Apr 21;23(1):256. doi: 10.1186/s12879-023-08209-9.