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Fosfomycin single- and multiple-dose pharmacokinetics in patients undergoing prolonged intermittent renal replacement

Lisa K V Gerecke1, Julius J Schmidt2, Carsten Hafer1

  • 1Medical Clinic V | Nephrology | Rheumatology | Blood Purification, Academic Teaching Hospital Braunschweig, Braunschweig, Germany.

The Journal of Antimicrobial Chemotherapy
|September 29, 2021
PubMed
Abstract

Insights

Fosfomycin is significantly cleared during prolonged intermittent renal replacement therapy (PIRRT), necessitating specific dosing. Careful monitoring is crucial to avoid drug accumulation in patients undergoing PIRRT.

Area of Science:

  • Pharmacology
  • Nephrology
  • Infectious Diseases

Background:

  • Fosfomycin is increasingly used for multidrug-resistant (MDR) bacteria.
  • Renal excretion is the primary elimination route for fosfomycin.
  • Dosing guidelines for fosfomycin in patients on modern renal replacement therapies are limited.

Purpose of the Study:

  • To evaluate the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT).
  • To establish evidence-based fosfomycin dosing recommendations for patients on PIRRT.

Main Methods:

  • Pharmacokinetic analysis of fosfomycin in 11 patients receiving PIRRT.
  • Measurement of plasma fosfomycin levels and dialysate concentrations at multiple time points.
  • Calculation of fosfomycin clearance and half-life during PIRRT.

Main Results:

  • Fosfomycin exhibited a median plasma dialyser clearance of 183.4 mL/min during PIRRT.
  • Approximately 73.9% of the fosfomycin dose was eliminated via the dialyser.
  • The median fosfomycin half-life was 2.5 hours, with 100% T>MIC achieved in all patients.

Conclusions:

  • Patients on PIRRT experience substantial fosfomycin elimination.
  • A fosfomycin dose of 5g every 8 hours is suggested to achieve adequate plasma levels.
  • Potential for drug accumulation exists, influenced by dialysis frequency and intensity.

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