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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 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：哪些抗微生物剂提供最佳功效，安全,复杂的腹腔内感染（cIAI）的经验治疗的耐受性尚不清楚，但在不断发展的抗菌药物耐药性的背景下至关重要。因此,关于这个问题的最新荟萃分析是必要的.
方法：我们系统地搜索了四个主要的电子数据库，从它们开始到2022年10月。包括研究cIAI治疗用抗菌药物的随机对照试验。两名审稿人利用Cochrane协作手册更新版本1中所述的Cochrane协作偏差风险工具独立评估纳入研究的质量，并根据预定的主题列表从所有手稿中提取数据。所有meta分析均使用R软件进行。主要结果是cIAIs患者的临床成功率。
结果：在网络荟萃分析中纳入了45项具有低到中等方法学质量的主动对照试验，涉及14,267名患有cIAIs的成年人。绝大多数急性生理学和慢性健康评估II评分<10的患者治疗失败或死亡的风险较低。研究了21种方案。在网络荟萃分析中，头孢吡肟联合甲硝唑的疗效优于替加环素和头孢洛嗪/他唑巴坦联合甲硝唑（比值比[OR]=1.96，95％可信区间[CrI]1.05〜3.79；OR=3.09，95％CrI1.02〜9.79，分别为）。在微生物成功率方面，在抗微生物剂之间没有发现统计学上的显着差异。头孢吡肟联合甲硝唑的全因死亡风险低于替加环素(OR=0.22,95%CrI0.05~0.85)。观察到具有统计学意义的趋势有利于头孢噻肟加甲硝唑，与埃拉环素相比，因不良事件（AE）而停药的次数较少，美罗培南和头孢洛扎/他唑巴坦加甲硝唑（分别为OR=0.0，95％CrI0.0〜0.8；OR=0.0，95％CrI0.0〜0.7；OR=0.0，95％CrI0.0〜0.64）。与替加环素相比,埃拉环素因不良事件而停药较少(OR=0.17,95%CrI0.03~0.81)。与美罗培南相比，头孢他啶/阿维巴坦加甲硝唑因不良事件而停药率较高（OR=2.09，95％CrI1.0〜4.41）。在成对荟萃分析中，与头孢曲松加甲硝唑相比，厄他培南和莫西沙星(一项试验，OR=1.93，95%CI1.06~3.50；一项试验，OR=4.24，95%CI分别为1.18~15.28）与严重AE风险显著增加相关。与亚胺培南/西司他丁相比，替加环素(四项试验，OR=1.57，95CI1.07~2.32）与严重AE的风险明显增加相关。根据累积排序曲线下的曲面，就疗效和安全性而言，头孢吡肟加甲硝唑在所有治疗中更可能是最佳的。就耐受性而言，替加环素更可能是最差的方案，埃拉环素的耐受性较好.
结论：这项研究表明，头孢吡肟联合甲硝唑是cIAIs患者经验性治疗的最佳选择，考虑到安全性和耐受性，替加环素的处方应谨慎。然而,应该指出的是，目前可用的有效性数据，安全,抗菌药物的耐受性主要与低风险的cIAIs患者有关。
方法：我们系统地搜索了四个主要的电子数据库，从它们开始到2022年10月。包括研究cIAI治疗用抗菌药物的随机对照试验。两名审稿人利用Cochrane协作手册更新版本1中所述的Cochrane协作偏差风险工具独立评估纳入研究的质量，并根据预定的主题列表从所有手稿中提取数据。所有meta分析均使用R软件进行。主要结果是cIAIs患者的临床成功率。
结果：在网络荟萃分析中纳入了45项具有低到中等方法学质量的主动对照试验，涉及14,267名患有cIAIs的成年人。绝大多数急性生理学和慢性健康评估II评分<10的患者治疗失败或死亡的风险较低。研究了21种方案。在网络荟萃分析中，头孢吡肟联合甲硝唑的疗效优于替加环素和头孢洛嗪/他唑巴坦联合甲硝唑（比值比[OR]=1.96，95％可信区间[CrI]1.05〜3.79；OR=3.09，95％CrI1.02〜9.79，分别为）。在微生物成功率方面，在抗微生物剂之间没有发现统计学上的显着差异。头孢吡肟联合甲硝唑的全因死亡风险低于替加环素(OR=0.22,95%CrI0.05~0.85)。观察到具有统计学意义的趋势有利于头孢噻肟加甲硝唑，与埃拉环素相比，因不良事件（AE）而停药的次数较少，美罗培南和头孢洛扎/他唑巴坦加甲硝唑（分别为OR=0.0，95％CrI0.0〜0.8；OR=0.0，95％CrI0.0〜0.7；OR=0.0，95％CrI0.0〜0.64）。与替加环素相比,埃拉环素因不良事件而停药较少(OR=0.17,95%CrI0.03~0.81)。与美罗培南相比，头孢他啶/阿维巴坦加甲硝唑因不良事件而停药率较高（OR=2.09，95％CrI1.0〜4.41）。在成对荟萃分析中，与头孢曲松加甲硝唑相比，厄他培南和莫西沙星(一项试验，OR=1.93，95%CI1.06~3.50；一项试验，OR=4.24，95%CI分别为1.18~15.28）与严重AE风险显著增加相关。与亚胺培南/西司他丁相比，替加环素(四项试验，OR=1.57，95CI1.07~2.32）与严重AE的风险明显增加相关。根据累积排序曲线下的曲面，就疗效和安全性而言，头孢吡肟加甲硝唑在所有治疗中更可能是最佳的。就耐受性而言，替加环素更可能是最差的方案，埃拉环素的耐受性较好.
结论：这项研究表明，头孢吡肟联合甲硝唑是cIAIs患者经验性治疗的最佳选择，考虑到安全性和耐受性，替加环素的处方应谨慎。然而,应该指出的是，目前可用的有效性数据，安全,抗菌药物的耐受性主要与低风险的cIAIs患者有关。
