PDF(Pubmed)
Abstract：
Pharmacokinetic/pharmacodynamic (PK/PD) indices are widely used for the selection of optimum antibiotic doses. For β-lactam antibiotics, fT>MIC, best relates antibiotic exposure to efficacy and is widely used to guide the dosing of β-lactam/β-lactamase inhibitor (BLI) combinations, often without considering any PK/PD exposure requirements for BLIs.
This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with β-lactam antibiotics.
Literature was searched online through PubMed, Embase, Web of Science, Scopus and Cochrane Library databases up to 5 June 2023. Studies that report the PK/PD index and threshold concentration of BLIs approved for clinical use were included. Narrative data synthesis was carried out to assimilate the available evidence.
Twenty-three studies were included. The PK/PD index that described the efficacy of BLIs was fT>CT for tazobactam, avibactam and clavulanic acid and fAUC0-24/MIC for relebactam and vaborbactam. The optimal magnitude of the PK/PD index is variable for each BLI based on the companion β-lactam antibiotics, type of bacteria and β-lactamase enzyme gene transcription levels.
The PK/PD index that describes the efficacy of BLIs and the exposure measure required for their efficacy is variable among inhibitors; as a result, it is difficult to make clear inference on what the optimum index is. Further PK/PD profiling of BLI, using preclinical infection models that simulate the anticipated mode(s) of clinical use, is warranted to streamline the exposure targets for use in the optimization of dosing regimens.
This systematic review aimed to describe the PK/PD exposure requirements of BLIs for optimal microbiological efficacy when used in combination with β-lactam antibiotics.
Literature was searched online through PubMed, Embase, Web of Science, Scopus and Cochrane Library databases up to 5 June 2023. Studies that report the PK/PD index and threshold concentration of BLIs approved for clinical use were included. Narrative data synthesis was carried out to assimilate the available evidence.
Twenty-three studies were included. The PK/PD index that described the efficacy of BLIs was fT>CT for tazobactam, avibactam and clavulanic acid and fAUC0-24/MIC for relebactam and vaborbactam. The optimal magnitude of the PK/PD index is variable for each BLI based on the companion β-lactam antibiotics, type of bacteria and β-lactamase enzyme gene transcription levels.
The PK/PD index that describes the efficacy of BLIs and the exposure measure required for their efficacy is variable among inhibitors; as a result, it is difficult to make clear inference on what the optimum index is. Further PK/PD profiling of BLI, using preclinical infection models that simulate the anticipated mode(s) of clinical use, is warranted to streamline the exposure targets for use in the optimization of dosing regimens.
摘要：
背景：药代动力学/药效学（PK/PD）指数广泛用于选择最佳抗生素剂量。对于β-内酰胺类抗生素，fT>MIC，最佳相关抗生素暴露的功效，并广泛用于指导β-内酰胺/β-内酰胺酶抑制剂（BLI）组合的剂量，通常不考虑BLIs的任何PK/PD暴露要求。
目的：本系统综述旨在描述BLIs与β-内酰胺类抗生素联合使用时最佳微生物功效的PK/PD暴露要求。
方法：通过PubMed在线搜索文献，Embase,WebofScience,截至2023年6月5日，Scopus和Cochrane图书馆数据库。包括报告批准用于临床使用的BLI的PK/PD指数和阈值浓度的研究。进行了叙事数据综合以吸收现有证据。
结果：纳入了23项研究。描述BLIs疗效的PK/PD指数为fT>他唑巴坦的CT，阿维巴坦和克拉维酸和fAUC0-24/MIC用于relebactam和vaborbactam。基于伴随的β-内酰胺抗生素，每个BLI的PK/PD指数的最佳幅度是可变的。细菌类型和β-内酰胺酶基因转录水平。
结论：描述BLIs疗效的PK/PD指数及其疗效所需的暴露量在抑制剂之间是可变的；因此，很难明确推断最佳指标是什么。BLI的进一步PK/PD分析，使用模拟临床使用预期模式的临床前感染模型，有必要简化暴露目标，以用于优化给药方案。
目的：本系统综述旨在描述BLIs与β-内酰胺类抗生素联合使用时最佳微生物功效的PK/PD暴露要求。
方法：通过PubMed在线搜索文献，Embase,WebofScience,截至2023年6月5日，Scopus和Cochrane图书馆数据库。包括报告批准用于临床使用的BLI的PK/PD指数和阈值浓度的研究。进行了叙事数据综合以吸收现有证据。
结果：纳入了23项研究。描述BLIs疗效的PK/PD指数为fT>他唑巴坦的CT，阿维巴坦和克拉维酸和fAUC0-24/MIC用于relebactam和vaborbactam。基于伴随的β-内酰胺抗生素，每个BLI的PK/PD指数的最佳幅度是可变的。细菌类型和β-内酰胺酶基因转录水平。
结论：描述BLIs疗效的PK/PD指数及其疗效所需的暴露量在抑制剂之间是可变的；因此，很难明确推断最佳指标是什么。BLI的进一步PK/PD分析，使用模拟临床使用预期模式的临床前感染模型，有必要简化暴露目标，以用于优化给药方案。
