The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats.
The effect of coadministration of fosfomycin (FOM) on glycopeptide antibiotic-induced nephrotoxicity for 3 days was investigated in rats. To induce nephrotoxicity in a short time, gentamicin (GM) was also coadministered. In the present study, FOM decreased glycopeptide antibiotic-induced nephrotoxicity as shown by reduced urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) as well as fewer histopathological signs of nephrotoxicity in the groups treated with the combination of glycopeptide and FOM as compared with a glycopeptide alone. In addition, the higher the dose of FOM, the more it decreased urinary NAG levels, suggesting that the role of FOM in alleviating nephrotoxicity is dose dependent. The accumulation of teicoplanin and vancomycin was significantly lower in the renal cortex of rats treated with the combination of glycopeptide antibiotics and FOM as compared with glycopeptide antibiotics alone (P < 0.05). In conclusion, the concomitant administration of FOM and glycopeptide antibiotics may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of glycopeptide antibiotics.
Yoshiyama
Y
Y
Division of Clinical Pharmacy, Kyoritsu College of Pharmacy, 1-15-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. yoshiyama-yj@kyoritsu-ph.ac.jp
Yazaki
T
T
Wong
P C
PC
Beauchamp
D
D
Kanke
M
M
D000118:Acetylglucosaminidase / Q000378:metabolism / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000494:pharmacology* / Q000633:toxicity; D005578:Fosfomycin / Q000008:administration & dosage / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity; D006651:Histocytochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017334:Teicoplanin / Q000378:metabolism; D014640:Vancomycin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D005578:Fosfomycin; D017334:Teicoplanin; D014640:Vancomycin; D000118:Acetylglucosaminidase