Hägglund Malin, Snygg-Martin Ulrika, Olaison Lars, Stofkoper Michael, Larsson Bert Ove, Brink Magnus
Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Diagnosvägen 21, SE-41650 Gothenburg, Sweden.
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10a, SE-40234 Gothenburg, Sweden.
Antibiotics (Basel). 2025 Jan 9;14(1):56. doi: 10.3390/antibiotics14010056.
Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR.
Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented.
A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients.
This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR.
目前用于感染性心内膜炎（IE）的抗生素治疗方案有效，但存在迟发型超敏反应（DHR）的高风险。通过治疗药物监测（TDM）指导剂量调整可在维持治疗效果的同时降低这些风险。本研究旨在调查IE患者中苄青霉素和氯唑西林的血浆浓度，并探讨抗生素浓度与DHR之间的关联。
在IE患者治疗的第一周和第三周，测量苄青霉素和氯唑西林的血浆浓度，分别作为中心浓度（连续剂量之间的中点浓度）和谷值浓度。记录患者的特征和结局，包括DHR。
共纳入55例患者，其中37例（67%）接受苄青霉素治疗，18例（33%）接受氯唑西林治疗。90天死亡率为3%。两种抗生素的中心浓度和谷值浓度在患者之间均表现出较大差异，而大多数患者在第1周和第3周之间的个体内变异性较低。肾功能最多只能解释54%的变异性，包含肾功能、体重指数、年龄和白蛋白的多元回归模型最多可解释苄青霉素68%的变异性。血浆高浓度与DHR的发生率之间没有关系；相反，我们观察到这些患者血浆浓度有偏低的趋势。
本研究揭示了所研究的两种青霉素血浆浓度存在显著的个体间差异。在浓度难以预测的情况下，如严重肥胖或肾衰竭，TDM可能有用。此外，我们没有发现血浆高浓度与DHR发生率相关的迹象。
