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Abstract：
BACKGROUND: The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based regimen in these patients.
METHODS: Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3.
RESULTS: In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I2 = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes.
CONCLUSIONS: TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required.
BACKGROUND: Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.
METHODS: Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3.
RESULTS: In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I2 = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes.
CONCLUSIONS: TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required.
BACKGROUND: Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.
摘要：
背景：基于治疗药物监测（TDM）的抗菌药物给药优化策略对危重患者的药代动力学/药效学和特定药物特性的有效性尚不清楚。这里,我们对随机对照试验进行了系统回顾和荟萃分析,以评估基于TDM的治疗方案在这些患者中的有效性.
方法：系统检索来自三个数据库的文章，以确定相关的随机对照研究。用于评估随机试验中偏倚风险的Cochrane工具的第二版用于评估分析中包含的研究中的偏倚风险。证据质量评估使用建议分级评估进行分级，发展,和评价方法。主要结局是28天死亡率，次要结局是院内死亡率。临床治愈,在重症监护病房（ICU）的住院时间和第1天和第3天的目标达成情况。
结果：总计，纳入5项涉及1011例患者的研究，用于主要结局的荟萃分析，其中以TDM为基础的方案组和对照组之间无显著差异(风险比[RR]0.94,95%置信区间[CI]:0.77~1.14;I2=0%).住院死亡率（RR0.96，95%CI：0.76-1.20），临床治愈（RR1.23，95%CI：0.91-1.67），ICU住院时间（平均差0，95%CI：-2.18-2.19），第1天（RR1.14，95%CI：0.88-1.48）和第3天（RR1.35，95%CI：0.90-2.03）的目标达成情况两组间无显著差异，次要结局的所有证据的确定性水平都很低或非常低，因为纳入的研究存在严重的偏倚风险，结果定义的变化，和小样本量。
结论：以TDM为基础的方案对临床或药理结局无显著疗效。需要进一步研究其他可实现的目标和明确的结果。
背景：临床试验注册；PROSPERO（https://www.crd.约克。AC.英国/繁荣/)，注册编号：CRD42022371959。2022年11月24日注册。
方法：系统检索来自三个数据库的文章，以确定相关的随机对照研究。用于评估随机试验中偏倚风险的Cochrane工具的第二版用于评估分析中包含的研究中的偏倚风险。证据质量评估使用建议分级评估进行分级，发展,和评价方法。主要结局是28天死亡率，次要结局是院内死亡率。临床治愈,在重症监护病房（ICU）的住院时间和第1天和第3天的目标达成情况。
结果：总计，纳入5项涉及1011例患者的研究，用于主要结局的荟萃分析，其中以TDM为基础的方案组和对照组之间无显著差异(风险比[RR]0.94,95%置信区间[CI]:0.77~1.14;I2=0%).住院死亡率（RR0.96，95%CI：0.76-1.20），临床治愈（RR1.23，95%CI：0.91-1.67），ICU住院时间（平均差0，95%CI：-2.18-2.19），第1天（RR1.14，95%CI：0.88-1.48）和第3天（RR1.35，95%CI：0.90-2.03）的目标达成情况两组间无显著差异，次要结局的所有证据的确定性水平都很低或非常低，因为纳入的研究存在严重的偏倚风险，结果定义的变化，和小样本量。
结论：以TDM为基础的方案对临床或药理结局无显著疗效。需要进一步研究其他可实现的目标和明确的结果。
背景：临床试验注册；PROSPERO（https://www.crd.约克。AC.英国/繁荣/)，注册编号：CRD42022371959。2022年11月24日注册。
