A synergistic effect of antibacterial activity has been demonstrated with piperacillin combined with an aminoglycoside. Four groups of 30 female Wistar rats were injected daily for 14 days with either gentamicin 50 mg/kg, or piperacillin 1,000 mg/kg, or both drugs combined; the control group received sodium chloride in solution. In all groups, creatinine clearance, lysosomal structural latency and renal cortex enzyme activities (alanine-aminopeptidase, N-acetyl beta D-glucosaminidase, sphingomyelinase, cathepsin B) were measured on days 2, 4, 7, 10 and 14 of treatment. Renal cortex concentrations of gentamicin were measured in the group that received gentamicin alone and in the group treated with both piperacillin and gentamicin. The renal functional changes usually induced by aminoglycosides were observed. Piperacillin administered alone reduced creatinine clearance and alanine-aminopeptidase activity. The piperacillin-gentamicin combination proved unable to prevent the fall in creatinine clearance; it also reduced the alanine-aminopeptidase, sphingomyelinase and cathepsin B activities, but the reduction was less pronounced than that induced by gentamicin alone.

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