Efficacy and safety of once daily versus intermittent dosing of tobramycin in rabbits with acute pyelonephritis.

Unilateral pyelonephritis was induced in 50 rabbits by injecting Escherichia coli (minimum inhibitory concentration of tobramycin 0.25 mg/l) into the left kidney and by obstructing the ureter temporarily. Tobramycin treatment (daily dose 10 mg/kg) was started 4 days after surgery, either in a single daily dose or in 3 divided doses at 8 h intervals, for 2, 3, 5, 7 or 10 days. Comparison of bacteriology, renal morphology, and renal functions (BUN, serum creatinine, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, cathepsin B, sphingomyelinase) suggests better efficacy and renal tolerance of the single daily dose regimen in the treatment of experimental acute pyelonephritis.

[Comparison of the efficacy of a single daily injection versus fractionated injections of ceftriaxone in the treatment of acute experimental pyelonephritis]. / Comparaison de l'efficacité de la ceftriaxone en injection quotidienne unique par rapport aux injections fractionnées dans le traitement des pyélonéphrites aiguës expérimentales.

Unilateral acute pyelonephritis were produced in rabbits by injecting E. coli, using the retrograde route and after a temporary ureteral obstruction. Animals were treated with ceftriaxone IM at a dose of 50 mg/kg/d and 100 mg/kg/d (corresponding to 1 g/d and 2 g/d in humans) either by a single daily injection or by two daily injections at 12th intervals. Sacrifices were performed at day 5 and 7 of therapy. Analysis of bacteriological, morphological and histological data obtained in infected kidneys demonstrates that the single daily injection of ceftriaxone is more effective than the same dose divided in two injections at 12 h intervals. These results are observed as well with low and high doses of ceftriaxone.

[Acute experimental pyelonephritis. Treatment with tobramycin. Influence of the rhythm of administration on efficacy and renal tolerability]. / Pyélonéphrite aiguë expérimentale. Traitement par tobramycine. Influence du rythme d'administration sur l'efficacité et la tolérance rénale.

Acute experimental pyelonephritis was produced in rabbits by injecting E. coli (tobramycin MIC 1 mg/l) into the left kidney and temporarily obstructing the ureter. Animals were given 10 mg/kg tobramycin intramuscularly 48 h after surgery and subsequently every day for 7, 10 or 15 days, either in a single daily dose or in three divided doses at 8 h intervals. Animals were killed 24 h after the last injection. Comparison of results shows that kidneys were sterilized by a single daily dose but not by three divided daily doses. In rabbits given the single daily dose regimen, kidneys recovered a normal macroscopical and histological aspect, serum anti-E. coli antibodies rose more slowly and less significantly, serum creatinine increased less, and renal enzymatic activities were restored (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase). These findings suggest better efficacy and renal tolerance of the single daily dose regimen as compared to the three daily divided dose regimen in the treatment of acute experimental pyelonephritis.