Protective effect of fosfomycin on the experimental nephrotoxicity induced by dibekacin.

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Abstract
Protection by fosfomycin [an antibiotic] of the nephrotoxicity of dibekacin was studied in Fischer 344 rats, and urinary parameters such as volume, osmolality, protein, N-acetyl-.beta.-D-glucosaminidase, leucine aminopeptidase, lactate dehydrogenase and nucleated cells were determined as markers of nephrotoxicity. The duration of treatment was 11 days. Fosfomycin reduced polyuria, proteinuria, enzymuria and cyturia induced by dibekacin best by the concomitant administration followed by pretreatment, but not by posttreatment. Protection was effective in the dose ratio of dibekacin: fosfomycin = 1:2-1:32, regardless of administration routes. As judged from urinalysis, protection by fosfomycin (320 mg/kg) was almost complete for the experimental nephrotoxicity induced by 10 mg/kg of dibekacin and was still significant for that by 40 mg/kg. This was supported by the histopathological and ultrastructural improvement of proximal tubules and by suppressed blood urea N and creatinine values. Protective activity of fosfomycin was more potent than that of cephalothin, when compared on the weight basis.

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