Service de Maladies Infectieuses Et Tropicales, Centre Hospitalier Annecy Genevois, Annecy, France.
Plateforme de Dosage Des Anti-Infectieux, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
Eur J Clin Microbiol Infect Dis. 2022 Sep;41(9):1183-1190. doi: 10.1007/s10096-022-04475-8. Epub 2022 Aug 19.
Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke's criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients' charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke's criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (p = 0.04)), and altered creatinine clearance was associated with overdosage (p = 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.
治疗感染性心内膜炎(IE)基于高剂量和长时间的抗生素治疗。治疗药物监测(TDM)可优化抗生素处方,实现个体化医疗,但目前尚无研究评估其在 IE 管理中的作用。我们进行了一项回顾性、双中心、描述性研究,时间范围为 2007 年 1 月至 2019 年 12 月。我们纳入了符合 Duke 标准的 IE 患者,并对其进行 TDM。通过患者病历回顾收集临床和微生物学数据。我们将目标浓度设定为 20 至 50mg/L。共纳入 322 例 IE 发作,涉及 306 例患者,其中 78.6%(253/326)根据 Duke 标准被认为是明确的。306 例患者中,60.5%(185/306)为原发性瓣膜受累,主动脉瓣受累占 46.6%(150/322),二尖瓣受累占 36.3%(117/322)。76.7%(247/322)的病例超声心动图阳性。TDM 后,322 例中有 51.5%(166/322)调整了剂量(减少 84.3%(140/166))。初始剂量后,阿莫西林和苯唑西林的使用中,分别有 46.3%(177/382)和 92.8%(56/60)被认为剂量过高。剂量过高的患者住院时间更长(25 天与 20 天,p=0.04),且改变的肌酐清除率与剂量过高相关(p=0.01)。我们的研究表明,目前的指南可能导致大多数患者的药物浓度过高。TDM 的益处主要在肾功能改变的患者中体现,但可能限制了大多数患者因剂量过高而产生的不良反应。