Dipartimento di Sicurezza e Bioetica - Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia; Department of Anaesthesiology, Critical Care and Perioperative Medicine, Nancy University Hospital, Nancy, France; SIMPA, Université de Lorraine, Vandoeuvre les Nancy, France.
Int J Antimicrob Agents. 2024 Sep;64(3):107266. doi: 10.1016/j.ijantimicag.2024.107266. Epub 2024 Jul 5.
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.
To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam.
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.
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.
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.
新型β-内酰胺类药物对许多引起严重肺部感染的多重耐药革兰氏阴性菌具有活性。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。
描述和评价报告头孢地尔、头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦、亚胺培南/西司他丁/雷巴他定和美罗培南/沃巴坦肺部药代动力学和药效学数据的研究。
使用 MEDLINE（PubMed）、Embase、Web of Science 和 Scopus 库进行文献检索。纳入已发表在同行评议期刊上的接受头孢地尔、头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦、亚胺培南/西司他丁/雷巴他定和美罗培南/沃巴坦治疗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。两名独立作者筛选、审查并从纳入的文章中提取数据。使用临床药代动力学研究报告指南（ClinPK 声明）评估偏倚。纳入了相关结局，如群体药代动力学参数和给药方案的目标达成率。
共纳入 24 篇文章。研究方法和结果报告存在异质性，不同研究对 ClinPK 声明检查表的遵循程度存在差异。头孢洛扎/他唑巴坦是研究最多的药物。只有两项研究从肺炎患者中采集了上皮衬液样本。其他所有的 I 期研究都招募了健康受试者。现有群体药代动力学模型中存在显著的群体异质性。大多数研究报告了使用当前许可的给药方案达到目标的概率在 90%以上。
尽管很少描述肺部药代动力学，但本综述观察到所有新型β-内酰胺类药物使用血浆药代动力学数据时的高目标达成率。未来的研究应描述有发生耐碳青霉烯病原体感染风险的患者人群中的肺部药代动力学。
