Marx Kathrin, Malmström Nina, Quast Marie, Glas Annette, Wendt Ralph, Kinzig Martina, Sörgel Fritz, Fedders Maike, Bertsche Thilo, Lübbert Christoph
Hospital Pharmacy, Hospital St. Georg, 04129 Leipzig, Germany.
Department of Infectious Diseases and Tropical Medicine, Hospital St. Georg, 04129 Leipzig, Germany.
Antibiotics (Basel). 2025 May 27;14(6):548. doi: 10.3390/antibiotics14060548.
Fosfomycin is used as a combination partner for the treatment of severe non-urinary tract infections. Individualized dosing of fosfomycin based on therapeutic drug monitoring (TDM) has the potential to reduce drug-related adverse events (AEs). This retrospective study used routine data from patients receiving intravenous fosfomycin therapy. Plasma concentrations of fosfomycin were categorized into three different ranges: <64 mg/L, 64-128 mg/L, and >128 mg/L. Subsequently, the influence of acute kidney injury (AKI) on reaching the specific plasma concentration ranges and the occurrence of AEs was analyzed. The study included 143 patients (median age 73 years, 66.4% male) with fosfomycin plasma measurements. Beta-lactam antibiotics were most frequently used in combination (62.2%), followed by tetracyclines (12.2%), cotrimoxazole (8.1%), and other agents (17.5%). Fosfomycin concentrations were >128 mg/L in 45% (36/80) of patients with normal renal function, 70.4% (38/54) of patients with AKI stages I to III, and 77.8% (7/9) of patients with renal replacement therapy. AEs occurred in 54% (77/143), mainly hypernatremia (42.6%), hypokalemia (39.9%), and gastrointestinal symptoms (19.6%), with the median fosfomycin plasma concentration being significantly higher in patients with AEs (158 mg/L vs. 131 mg/L, = 0.01). Multivariate logistic regression analysis revealed that patients aged ≥70 years (OR 3.70, 95% CI 1.24-11.5; = 0.02) and patients with fosfomycin plasma concentrations > 128 mg/L (OR 3.30, 95% CI 1.09-10.4; = 0.04) had a higher risk of AEs. There was a significant association between high plasma exposure and the occurrence of AEs. In particular, the impact of acute renal insufficiency on fosfomycin plasma concentrations should be considered. Individualized fosfomycin dosing based on TDM and the intensive monitoring of renal function contribute to reducing drug-related side effects.
磷霉素用作治疗严重非尿路感染的联合用药。基于治疗药物监测（TDM）的磷霉素个体化给药有可能减少药物相关不良事件（AE）。这项回顾性研究使用了接受静脉注射磷霉素治疗患者的常规数据。磷霉素的血浆浓度分为三个不同范围：<64mg/L、64 - 128mg/L和>128mg/L。随后，分析了急性肾损伤（AKI）对达到特定血浆浓度范围以及AE发生的影响。该研究纳入了143例有磷霉素血浆测量值的患者（中位年龄73岁，男性占66.4%）。联合使用最多的是β-内酰胺类抗生素（62.2%），其次是四环素类（12.2%）、复方新诺明（8.1%）和其他药物（17.5%）。肾功能正常的患者中45%（36/80）的磷霉素浓度>128mg/L，AKI I至III期患者中70.4%（38/54），接受肾脏替代治疗的患者中77.8%（7/9）。AE发生在54%（77/143）的患者中，主要是高钠血症（42.6%）、低钾血症（39.9%）和胃肠道症状（19.6%），发生AE的患者磷霉素血浆中位浓度显著更高（158mg/L对131mg/L，P = 0.01）。多因素逻辑回归分析显示，年龄≥70岁的患者（OR 3.70，95%CI 1.24 - 11.5；P = 0.02）和磷霉素血浆浓度>128mg/L的患者（OR 3.30，95%CI 1.09 - 10.4；P = 0.04）发生AE的风险更高。血浆高暴露与AE的发生之间存在显著关联。特别是，应考虑急性肾功能不全对磷霉素血浆浓度的影响。基于TDM的磷霉素个体化给药以及对肾功能的密切监测有助于减少药物相关副作用。
