Abstract
Serum, urine and renal levels of fleroxacin were evaluated in normal andEscherichia coli-infected kidneys from 1 to 48 hours after either a single or 14 (every 12 hours) injections of 50 mg/kg. All treatments were started 24 hours after the induction of infection. Fleroxacin did not accumulate in normal or infected renal tissue, with serum and tissue concentrations of fleroxacin lower than the limit of detection 24 hours after the cessation of therapy. Following a single injection, the area under the concentration curves of fleroxacin in the serum, cortex and medulla of infected animals were significantly higher than those in normal rats (P<0.05) and peak concentrations of fleroxacin in the cortex and the medulla were greater than 800 times the MIC of theE. coli strain, and remained above the MIC for 12 hours after the cessation of therapy. Fleroxacin given twice a day at a dose of 25 mg/kg or as a single daily dose of 50 mg/kg for 14 days sterilized 100% of the infected kidneys and urines for up to 6 months following the cessation of therapy. These 2 regimens were more effective than alternative therapy with tobramycin (10 mg/kg every 12 hours for 3 days) combined with trimethoprim (10 mg/kg every 12 hours for 14 days). However, fleroxacin, at 50 mg/kg every 48 hours, was no more effective than the combination of tobramycin and trimethoprim. These results demonstrate that the intrarenal distribution of fleroxacin is altered in the presence of pyelonephritis. The long tissue half-life combined with a high therapeutic ratio permits single daily fleroxacin dosing in patients with severe pyelonephritis.
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Leclerc, F., Morin, N.J., Bergeron, M.G. et al. Relationship between intrarenal distribution and efficacy of fleroxacin in the treatment ofEscherichia coli pyelonephritis in rats. J Infect Chemother 4, 188–194 (1998). https://doi.org/10.1007/BF02490165
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DOI: https://doi.org/10.1007/BF02490165