Abstract：
BACKGROUND: Novel beta-lactams show activity against many multidrug-resistant Gram-negative bacteria that cause severe lung infections. Understanding pharmacokinetic/pharmacodynamic characteristics of these agents may help optimise outcomes in the treatment of pneumonia.
OBJECTIVE: To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam.
METHODS: MEDLINE (PubMed), Embase, Web of Science and Scopus libraries were used for the literature search. Pulmonary population pharmacokinetic and pharmacokinetic/pharmacodynamic studies on adult patients receiving cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam published in peer-reviewed journals were included. Two independent authors screened, reviewed and extracted data from included articles. A reporting guideline for clinical pharmacokinetic studies (ClinPK statement) was used for bias assessment. Relevant outcomes were included, such as population pharmacokinetic parameters and probability of target attainment of dosing regimens.
RESULTS: Twenty-four articles were included. There was heterogeneity in study methods and reporting of results, with diversity across studies in adhering to the ClinPK statement checklist. Ceftolozane/tazobactam was the most studied agent. Only two studies collected epithelial lining fluid samples from patients with pneumonia. All the other phase I studies enrolled healthy subjects. Significant population heterogeneity was evident among available population pharmacokinetic models. Probabilities of target attainment rates above 90% using current licensed dosing regiments were reported in most studies.
CONCLUSIONS: Although lung pharmacokinetics was rarely described, this review observed high target attainment using plasma pharmacokinetic data for all novel beta-lactams. Future studies should describe lung pharmacokinetics in patient populations at risk of carbapenem-resistant pathogen infections.
OBJECTIVE: To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam.
METHODS: MEDLINE (PubMed), Embase, Web of Science and Scopus libraries were used for the literature search. Pulmonary population pharmacokinetic and pharmacokinetic/pharmacodynamic studies on adult patients receiving cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam published in peer-reviewed journals were included. Two independent authors screened, reviewed and extracted data from included articles. A reporting guideline for clinical pharmacokinetic studies (ClinPK statement) was used for bias assessment. Relevant outcomes were included, such as population pharmacokinetic parameters and probability of target attainment of dosing regimens.
RESULTS: Twenty-four articles were included. There was heterogeneity in study methods and reporting of results, with diversity across studies in adhering to the ClinPK statement checklist. Ceftolozane/tazobactam was the most studied agent. Only two studies collected epithelial lining fluid samples from patients with pneumonia. All the other phase I studies enrolled healthy subjects. Significant population heterogeneity was evident among available population pharmacokinetic models. Probabilities of target attainment rates above 90% using current licensed dosing regiments were reported in most studies.
CONCLUSIONS: Although lung pharmacokinetics was rarely described, this review observed high target attainment using plasma pharmacokinetic data for all novel beta-lactams. Future studies should describe lung pharmacokinetics in patient populations at risk of carbapenem-resistant pathogen infections.
摘要：
背景：新型β-内酰胺对许多引起严重肺部感染的多重耐药革兰氏阴性菌显示出活性。了解这些药物的药代动力学/药效学特征可能有助于优化肺炎治疗的结果。
目的：为了描述和评价报告头孢地洛肺药代动力学和药效学数据的研究，头孢他啶/阿维巴坦,头孢洛赞/他唑巴坦,亚胺培南/西司他丁/来巴坦和美罗培南/伐巴坦。
方法：MEDLINE（PubMed），Embase,使用WebofScience和Scopus图书馆进行文献检索。接受头孢地洛的成年患者的肺部群体药代动力学和药代动力学/药效学研究，头孢他啶/阿维巴坦,头孢洛赞/他唑巴坦,亚胺培南/西司他丁/来巴坦，包括在同行评审期刊上发表的美罗培南/伐巴坦。两名独立作者筛选，reviewed,并从包含的文章中提取数据。临床药代动力学研究的报告指南（ClinPK声明）用于偏倚评估。包括相关结果，如群体药代动力学参数和给药方案达到目标的概率。
结果：纳入24篇文章。研究方法和结果报告存在异质性，在坚持ClinPK声明清单的研究中具有多样性。头孢洛赞/他唑巴坦是研究最多的药物。只有两项研究收集了肺炎患者的上皮衬里液样本。所有其他I期研究都招募了健康受试者。在可用的群体药代动力学模型中，显著的群体异质性是明显的。在大多数研究中报道了使用当前许可的给药方案的目标达到率高于90%的概率。
结论：尽管很少描述肺部药代动力学，本综述使用所有新型β-内酰胺类的血浆药代动力学数据观察到高目标达成率.未来的研究应描述有碳青霉烯类耐药病原体感染风险的患者人群的肺部药代动力学。
目的：为了描述和评价报告头孢地洛肺药代动力学和药效学数据的研究，头孢他啶/阿维巴坦,头孢洛赞/他唑巴坦,亚胺培南/西司他丁/来巴坦和美罗培南/伐巴坦。
方法：MEDLINE（PubMed），Embase,使用WebofScience和Scopus图书馆进行文献检索。接受头孢地洛的成年患者的肺部群体药代动力学和药代动力学/药效学研究，头孢他啶/阿维巴坦,头孢洛赞/他唑巴坦,亚胺培南/西司他丁/来巴坦，包括在同行评审期刊上发表的美罗培南/伐巴坦。两名独立作者筛选，reviewed,并从包含的文章中提取数据。临床药代动力学研究的报告指南（ClinPK声明）用于偏倚评估。包括相关结果，如群体药代动力学参数和给药方案达到目标的概率。
结果：纳入24篇文章。研究方法和结果报告存在异质性，在坚持ClinPK声明清单的研究中具有多样性。头孢洛赞/他唑巴坦是研究最多的药物。只有两项研究收集了肺炎患者的上皮衬里液样本。所有其他I期研究都招募了健康受试者。在可用的群体药代动力学模型中，显著的群体异质性是明显的。在大多数研究中报道了使用当前许可的给药方案的目标达到率高于90%的概率。
结论：尽管很少描述肺部药代动力学，本综述使用所有新型β-内酰胺类的血浆药代动力学数据观察到高目标达成率.未来的研究应描述有碳青霉烯类耐药病原体感染风险的患者人群的肺部药代动力学。
