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The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats

Y Yoshiyama1, T Yazaki, P C Wong

  • 1Division of Clinical Pharmacy, Kyoritsu College of Pharmacy, 1-15-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. yoshiyama-yj@kyoritsu-ph.ac.jp

Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy
|January 26, 2002
PubMed

Insights

Fosfomycin (FOM) reduces glycopeptide antibiotic-induced kidney damage in rats. This protective effect is dose-dependent, lowering nephrotoxicity markers and drug accumulation in the kidneys.

Area of Science:

  • Pharmacology
  • Nephrology
  • Toxicology

Background:

  • Glycopeptide antibiotics like vancomycin and teicoplanin are crucial for treating serious bacterial infections.
  • However, their use is often limited by significant nephrotoxicity, posing a clinical challenge.
  • Developing strategies to mitigate antibiotic-induced kidney damage is essential for patient safety.

Purpose of the Study:

  • To investigate the potential of fosfomycin (FOM) to reduce glycopeptide antibiotic-induced nephrotoxicity.
  • To determine if FOM's effect on nephrotoxicity is dose-dependent.
  • To assess the impact of FOM on the accumulation of glycopeptide antibiotics in the renal cortex.

Main Methods:

  • Nephrotoxicity was induced in rats using glycopeptide antibiotics and gentamicin.
  • Fosfomycin (FOM) was coadministered at varying doses.
  • Urinary N-acetyl-beta-D-glucosaminidase (NAG) levels and renal histopathology were evaluated.
  • Teicoplanin and vancomycin accumulation in the renal cortex was measured.

Main Results:

  • Fosfomycin (FOM) significantly decreased glycopeptide antibiotic-induced nephrotoxicity.
  • Reduced urinary NAG excretion and fewer histopathological signs of kidney damage were observed with FOM coadministration.
  • FOM's protective effect was dose-dependent, with higher doses yielding greater reductions in NAG levels.
  • Accumulation of teicoplanin and vancomycin in the renal cortex was significantly lower when coadministered with FOM.

Conclusions:

  • Concomitant administration of fosfomycin (FOM) can mitigate glycopeptide antibiotic-induced nephrotoxicity.
  • FOM may represent a valuable component of a chemotherapeutic strategy to reduce the kidney toxicity associated with glycopeptide antibiotics.
  • The findings suggest a potential clinical benefit of combining FOM with glycopeptides to improve treatment safety.

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