Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study

Marx, Kathrin; Malmström, Nina; Quast, Marie; Glas, Annette; Wendt, Ralph; Kinzig, Martina; Sörgel, Fritz; Fedders, Maike; Bertsche, Thilo; Lübbert, Christoph

doi:10.3390/antibiotics14060548

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Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study

by

Kathrin Marx

¹,

Nina Malmström

²,

Marie Quast

¹,

Annette Glas

³,

Ralph Wendt

⁴

,

Martina Kinzig

⁵,

Fritz Sörgel

^5,6,

Maike Fedders

¹,

Thilo Bertsche

^7,8

and

Christoph Lübbert

^2,9,10,*

¹

Hospital Pharmacy, Hospital St. Georg, 04129 Leipzig, Germany

²

Department of Infectious Diseases and Tropical Medicine, Hospital St. Georg, 04129 Leipzig, Germany

³

Department of Laboratory Medicine, Hospital St. Georg, 04129 Leipzig, Germany

⁴

Department of Nephrology, Hospital St. Georg, 04129 Leipzig, Germany

⁵

Institute for Biomedical and Pharmaceutical Research, 90562 Nuremberg, Germany

⁶

Institute of Pharmacology, West German Heart and Vascular Center, University of Duisburg-Essen, 45141 Essen, Germany

⁷

Department of Clinical Pharmacy, Institute of Pharmacy, Leipzig University, 04109 Leipzig, Germany

⁸

Drug Safety Center, Leipzig University Medical Center, 04103 Leipzig, Germany

⁹

Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Leipzig University Medical Center, 04103 Leipzig, Germany

¹⁰

Interdisciplinary Center for Infectious Diseases, Leipzig University Medical Center, 04103 Leipzig, Germany

^*

Author to whom correspondence should be addressed.

Antibiotics 2025, 14(6), 548; https://doi.org/10.3390/antibiotics14060548

Submission received: 15 April 2025 / Revised: 19 May 2025 / Accepted: 26 May 2025 / Published: 27 May 2025

(This article belongs to the Special Issue Antibiotics Use and Stewardship in Hospitals and Outpatient Care Facilities, 2nd Edition)

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Abstract

Background: 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). Methods: 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. Results: 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, p = 0.01). Multivariate logistic regression analysis revealed that patients aged ≥ 70 years (OR 3.70, 95% CI 1.24–11.5; p = 0.02) and patients with fosfomycin plasma concentrations > 128 mg/L (OR 3.30, 95% CI 1.09–10.4; p = 0.04) had a higher risk of AEs. Conclusions: 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.

Keywords: fosfomycin; therapeutic drug monitoring (TDM); acute kidney injury (AKI); renal failure; side effects; hypernatremia; hypokalemia; Staphylococcus aureus

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MDPI and ACS Style

Marx, K.; Malmström, N.; Quast, M.; Glas, A.; Wendt, R.; Kinzig, M.; Sörgel, F.; Fedders, M.; Bertsche, T.; Lübbert, C. Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study. Antibiotics 2025, 14, 548. https://doi.org/10.3390/antibiotics14060548

AMA Style

Marx K, Malmström N, Quast M, Glas A, Wendt R, Kinzig M, Sörgel F, Fedders M, Bertsche T, Lübbert C. Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study. Antibiotics. 2025; 14(6):548. https://doi.org/10.3390/antibiotics14060548

Chicago/Turabian Style

Marx, Kathrin, Nina Malmström, Marie Quast, Annette Glas, Ralph Wendt, Martina Kinzig, Fritz Sörgel, Maike Fedders, Thilo Bertsche, and Christoph Lübbert. 2025. "Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study" Antibiotics 14, no. 6: 548. https://doi.org/10.3390/antibiotics14060548

APA Style

Marx, K., Malmström, N., Quast, M., Glas, A., Wendt, R., Kinzig, M., Sörgel, F., Fedders, M., Bertsche, T., & Lübbert, C. (2025). Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study. Antibiotics, 14(6), 548. https://doi.org/10.3390/antibiotics14060548

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Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study

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