Abstract：
BACKGROUND: Therapeutic drug monitoring and Model-informed precision dosing allow dose individualization to increase drug effectivity and reduce toxicity.
OBJECTIVE: To evaluate the available evidence on the clinical efficacy of individualized antimicrobial dosing optimization.
METHODS: Data sources: PubMed, Embase, Web of Science, and Cochrane Library databases from database inception to 11 November 2022.
METHODS: Published peer-reviewed randomized controlled trials.
METHODS: Human subjects aged ≥18 years receiving an antibiotic or antifungal drug.
METHODS: Patients receiving individualized antimicrobial dose adjustment.
UNASSIGNED: Cochrane risk-of-bias tool for randomized trials.
UNASSIGNED: The primary outcome was the risk of mortality. Secondary outcomes included target attainment, treatment failure, clinical and microbiological cure, length of stay, treatment duration, and adverse events. Effect sizes were pooled using a random-effects model. Statistical heterogeneity was assessed by inconsistency testing (I2).
RESULTS: Ten randomized controlled trials were included in the meta-analysis (1241 participants; n = 624 in the individualized antimicrobial dosing group and n = 617 in the control group). Individualized antimicrobial dose optimization was associated with a numerical decrease in mortality (risk ratio [RR] = 0.86; 95% CI, 0.71-1.05), without reaching statistical significance. Moreover, it was associated with significantly higher target attainment rates (RR = 1.41; 95% CI, 1.13-1.76) and a significant decrease in treatment failure (RR = 0.70; 95% CI, 0.54-0.92). Individualized antimicrobial dose optimization was associated with improvement, but not significant in clinical cure (RR = 1.33; 95% CI, 0.94-1.33) and microbiological outcome (RR = 1.25; CI, 1.00-1.57), as well as with a significant decrease in the risk of nephrotoxicity (RR = 0.55; 95% CI, 0.31-0.97).
CONCLUSIONS: This meta-analysis demonstrated that target attainment, treatment failure, and nephrotoxicity were significantly improved in patients who underwent individualized antimicrobial dose optimization. It showed an improvement in mortality, clinical cure or microbiological outcome, although not significant.
OBJECTIVE: To evaluate the available evidence on the clinical efficacy of individualized antimicrobial dosing optimization.
METHODS: Data sources: PubMed, Embase, Web of Science, and Cochrane Library databases from database inception to 11 November 2022.
METHODS: Published peer-reviewed randomized controlled trials.
METHODS: Human subjects aged ≥18 years receiving an antibiotic or antifungal drug.
METHODS: Patients receiving individualized antimicrobial dose adjustment.
UNASSIGNED: Cochrane risk-of-bias tool for randomized trials.
UNASSIGNED: The primary outcome was the risk of mortality. Secondary outcomes included target attainment, treatment failure, clinical and microbiological cure, length of stay, treatment duration, and adverse events. Effect sizes were pooled using a random-effects model. Statistical heterogeneity was assessed by inconsistency testing (I2).
RESULTS: Ten randomized controlled trials were included in the meta-analysis (1241 participants; n = 624 in the individualized antimicrobial dosing group and n = 617 in the control group). Individualized antimicrobial dose optimization was associated with a numerical decrease in mortality (risk ratio [RR] = 0.86; 95% CI, 0.71-1.05), without reaching statistical significance. Moreover, it was associated with significantly higher target attainment rates (RR = 1.41; 95% CI, 1.13-1.76) and a significant decrease in treatment failure (RR = 0.70; 95% CI, 0.54-0.92). Individualized antimicrobial dose optimization was associated with improvement, but not significant in clinical cure (RR = 1.33; 95% CI, 0.94-1.33) and microbiological outcome (RR = 1.25; CI, 1.00-1.57), as well as with a significant decrease in the risk of nephrotoxicity (RR = 0.55; 95% CI, 0.31-0.97).
CONCLUSIONS: This meta-analysis demonstrated that target attainment, treatment failure, and nephrotoxicity were significantly improved in patients who underwent individualized antimicrobial dose optimization. It showed an improvement in mortality, clinical cure or microbiological outcome, although not significant.
摘要：
背景：治疗药物管理（TDM）和基于模型的精确给药（MIPD）允许剂量个体化以提高药物有效性并降低毒性。
目的：评估个体化抗菌药物给药优化的临床疗效的现有证据。
方法：数据源：发布，Embase,WebofScience,和Cochrane图书馆数据库从数据库开始到2022年11月11日。
方法：已发表同行评审的随机对照试验（RCT）。
方法：年龄≥18岁的受试者接受抗生素或抗真菌药物治疗。
方法：接受个体化抗菌药物剂量调整的患者。偏倚风险评估：用于随机试验的Cochrane偏倚风险工具（RoB2）。数据综合方法：主要结果是死亡风险。次要成果包括实现目标，治疗失败,临床和微生物治疗，逗留时间,治疗持续时间和不良事件。使用随机效应模型汇集效应大小。通过不一致性检验(I2)评估统计异质性。
结果：10个随机对照试验纳入荟萃分析（TDM组1,241名参与者；n=624，对照组中n=617)。个体化抗菌药物剂量优化与死亡率的数值下降相关(RR=0.86;95%CI0.71-1.05),没有达到统计学意义。此外，它与显著较高的目标达标率(RR=1.41;95%CI,1.13-1.76)和显著降低治疗失败(RR=0.70;95%CI,0.54-0.92)相关.个体化抗菌剂量优化也与改善有关，但在临床治愈（RR=1.33；95%CI，0.94-1.33）和微生物学结果（RR=1.25；CI，1.00-1.57）方面并不显著，以及肾毒性风险显着降低（RR=0.55;95％CI，0.31-0.97）。
结论：这项荟萃分析表明，治疗失败,在接受个体化抗菌药物剂量优化的患者中,肾毒性显著改善.然而,它没有显示死亡率的显著下降，临床治愈或微生物学结果。
目的：评估个体化抗菌药物给药优化的临床疗效的现有证据。
方法：数据源：发布，Embase,WebofScience,和Cochrane图书馆数据库从数据库开始到2022年11月11日。
方法：已发表同行评审的随机对照试验（RCT）。
方法：年龄≥18岁的受试者接受抗生素或抗真菌药物治疗。
方法：接受个体化抗菌药物剂量调整的患者。偏倚风险评估：用于随机试验的Cochrane偏倚风险工具（RoB2）。数据综合方法：主要结果是死亡风险。次要成果包括实现目标，治疗失败,临床和微生物治疗，逗留时间,治疗持续时间和不良事件。使用随机效应模型汇集效应大小。通过不一致性检验(I2)评估统计异质性。
结果：10个随机对照试验纳入荟萃分析（TDM组1,241名参与者；n=624，对照组中n=617)。个体化抗菌药物剂量优化与死亡率的数值下降相关(RR=0.86;95%CI0.71-1.05),没有达到统计学意义。此外，它与显著较高的目标达标率(RR=1.41;95%CI,1.13-1.76)和显著降低治疗失败(RR=0.70;95%CI,0.54-0.92)相关.个体化抗菌剂量优化也与改善有关，但在临床治愈（RR=1.33；95%CI，0.94-1.33）和微生物学结果（RR=1.25；CI，1.00-1.57）方面并不显著，以及肾毒性风险显着降低（RR=0.55;95％CI，0.31-0.97）。
结论：这项荟萃分析表明，治疗失败,在接受个体化抗菌药物剂量优化的患者中,肾毒性显著改善.然而,它没有显示死亡率的显著下降，临床治愈或微生物学结果。
