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Fosfomycin: Treatment of Urinary Tract Infections

Fosfomycin is a derivative of phosphonic acid and constitutes a separate pharmacological class of antibiotics.

Mechanism of Action of Fosfomycin

Fosfomycin inhibits an early step of the bactericidal cell wall synthesis (enzyme MurA).

Antibiotic Spectrum:

Escherichia coli, Citrobacter, Enterobacter, Klebsiella, Serratia, and Enterococcus spp. Partial sensitivity to ESBL and carbapenase-producing Enterobacteriaceae.

Urologic Indications for Fosfomycin

• Uncomplicated bladder infections in women, for bacteriuria or urinary tract infections during pregnancy.
• Off-label indications include treatment of complicated urinary tract infections (e.g., prostatitis) in cases of proven sensitivity, or prophylactic use in transrectal prostate biopsy.
• High-dose intravenous administration of fosfomycin (often in combination) is an option for severe and complicated infections when other antibiotics are considered ineffective.

Pharmacokinetics of Fosfomycin:

40% bioavailability when taken orally on an empty stomach with TRIS buffer (trometamol). Good tissue penetration. Low hepatic metabolism. Half-life 2–3 hours. Unchanged renal excretion with high urine concentration.

Side Effects of Fosfomycin

Fosfomycin is generally well tolerated. Possible side effects are rashes, acute hypersensitivity reactions, dysgeusia, vomiting, anorexia, diarrhea, liver enzyme elevation, headache, dizziness, and fatigue.

High-dose parenteral administration: high sodium load, hypokalemia, vein irritation, neutropenia, agranulocytosis, and anaphylaxis.

Contraindications of Fosfomycin:

• Intolerance to fosfomycin
• Children
• Renal insufficiency with a GFR below 10 ml/min.

Drug Interactions

Lower oral bioavailability is observed with prokinetics, such as metoclopramide.

Dosage of Fosfomycin

• Treatment of uncomplicated urinary tract infections: 3 g p.o. as a single dose.
• Oral off-label treatment of complicated urinary tract infections: 3 g p.o. every three days for 9–15 days, depending on the severity of the infection.
• Intravenous dosage for severe infections: 12(–24 g) per day in three divided doses i.v. depending on the severity of the disease. A dose reduction is necessary for patients with renal insufficiency:
  • 70% of the daily dosage with a GFR of 40–31 ml/min
  • 60% of the daily dosage with a GFR of 30–21 ml/min
  • 40% of the daily dosage with a GFR of 20–11 ml/min

References

H. R. Brodt, A. Hörauf, M. Kresken, W. Solbach, and T. Welte, Infektionstherapie: Antibiotika, Virostatika, Antimykotika, Antiparasitäre Wirkstoffe. Thieme, 2023.

S-3 Leitlinie Harnwegsinfektionen der DGU
Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten
AWMF, 2010, Register-Nr. 043/044

Patel u.a. 1997 PATEL, S. S. ; BALFOUR, J. A. ; BRYSON, H. M.: Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections.
In: Drugs
53 (1997), Nr. 4, S. 637–56

Stein 1998 STEIN, G. E.: Single-dose treatment of acute cystitis with fosfomycin tromethamine.
In: Ann Pharmacother
32 (1998), Nr. 2, S. 215–9

Zerbato V, Sanson G, Fusaro L, Gerussi V, Sincovich S, Dellai F, Del Fabro G, Geremia N, Maurel C, Giacomazzi D, Biasinutto C, Di Girolamo FG, Scrivo G, Costantino V, Di Santolo M, Busetti M, Crocè LS, Giuliano S, Crapis M, Zhanel G, Tascini C, Luzzati R, Di Bella S. Intravenous Fosfomycin for Difficult-to-Treat Infections: A Real-Life Multicentric Study in Italy. Antibiotics (Basel). 2025 Apr 14;14(4):401. doi: 10.3390/antibiotics14040401.

  Deutsche Version: Fosfomycin

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