[Can fosfomycin reduce the nephrotoxicity of aminoglycosides?]

Fosfomycin is an active antibiotic on Gram positive and Gram negative bacteria with a low toxicity in animals. To treat severe infections, it is recommended to associate fosfomycin with gentamicin. Wistar rats were given one of the following regimens for eight days : 100, 500 or 1 000 mg/kg fosfomycin, 50 mg/kg gentamicin or dibekacin, association of 100, 500, or 1 000 mg/kg fosfomycin and 50 mg/kg gentamicin or dibekacin. Control rats were given a saline solution. No renal histological alterations were identified with fosfomycin 100 mg/kg. Tubular dilatation and brush border rarefaction were observed with fosfomycin 500 and 1 000 mg/kg. These abnormalities did not seem related to fosfomycin itself but rather to the sodium load induced by fosfomycin treatment. A decrease in alanine aminopeptidase activity was noted for all doses of fosfomycin. Renal concentrations of gentamicin and dibekacin were not decreased by concomitant administration of fosfomycin. Fosfomycin, 100 mg/kg, did not change the nephrotoxic potential of gentamicin or dibekacin. Fosfomycin, 500 mg/kg, protected the kidney from the action of gentamicin or dibekacin. This effect seemed to be more pronounced for dibekacin than for gentamicin. Fosfomycin, 1 000 mg/kg, did not induce a more protective effect against the nephrotoxicity of these two aminoglycosides. Thus, we observed that fosfomycin combined with gentamicin or dibekacin reduced the degree of proximal tubular cell alterations, induced less modifications in alanine aminopeptidase, less lysosomal alterations, and a minor modification in sphingomyelinase activity.