Goutelle Sylvain, Conrad Anne, Pouderoux Cécile, Braun Evelyne, Laurent Frédéric, Gagnieu Marie-Claude, Cohen Sabine, Guitton Jérôme, Valour Florent, Ferry Tristan
Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France.
Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France.
Front Med (Lausanne). 2021 Mar 31;8:583086. doi: 10.3389/fmed.2021.583086. eCollection 2021.
Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime ( = 4), ertapenem ( = 4), and ceftriaxone ( = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.
对于革兰氏阴性骨与关节感染（BJI）患者，使用β-内酰胺类药物进行抑制性肠外抗生素治疗可能是必要的。皮下给药可在门诊环境中促进这种治疗，但关于这种做法的信息有限。我们基于治疗药物监测（TDM）和药代动力学/药效学（PK/PD）原理，开发了一种在此情况下的药物给药原始方法。本研究的目的是描述我们的方法及其在一个病例系列中的初步结果。我们分析了接受皮下（SC）途径β-内酰胺类药物抑制性抗生素治疗作为人工关节感染（PJI）挽救治疗且进行了基于PK/PD剂量调整的TDM的患者数据。2017年1月至2020年5月纳入了10名患者（6名女性和4名男性，平均年龄77岁）。通过SC途径给药的药物有头孢他啶（ = 4）、厄他培南（ = 4）和头孢曲松（ = 2）。在每位患者中，基于TDM和最低抑菌浓度（MIC）测量进行PK/PD指导的剂量个体化。在一些患者中，给药间隔可从每日两次延长至每周三次，同时保持PK/PD目标得以实现。在中位随访1035天（约3年）期间，10名患者中有9名患者的感染通过该策略得到了完全控制。随访期间没有患者获得对碳青霉烯类耐药的革兰氏阴性菌。1名患者在治疗期间出现获得性耐药导致治疗失败，回顾性分析其原因可能是MIC测定较晚且暴露不足。总之，我们基于模型的TDM、MIC测定和个体化PK/PD目标的创新方法，促进并优化了通过SC途径对PJI进行的门诊抑制性β-内酰胺类治疗。这些令人鼓舞的结果支持进行更大规模的临床评估。
