RESUMO
The intracortical, medullary, and papillary distribution of gentamicin was studied in normal and pyelonephritic rats. The animals were evaluated from 1 hr to 365 days after the end of therapy with either a single dose or two daily injections given every 12 hr for seven days. The serum levels of gentamicin at 1 hr were significantly (P less than 0.001) higher in the pyelonephritic rats than in the normal rats after one dose (26 vs. 12 microgram/ml) and 14 doses (25.7 vs. 8.8 microgram/ml). Peak concentrations or gentamicin in all parts of infected kidneys were significantly (P less than 0.001) higher than in normal kidneys. Gentamicin was still detectable at levels of 1.2 microgram/g in the cortex of one pyelonephritic animal one year after the end of therapy, when the levels of both serum creatinine (1.1 mg/100 ml) and blood urea nitrogen (30 mg/100 ml) were much higher than at seven days after the end of therapy (0.5 and 19 mg/100 ml, respectively).
Assuntos
Infecções por Escherichia coli/metabolismo , Gentamicinas/metabolismo , Córtex Renal/metabolismo , Medula Renal/metabolismo , Pielonefrite/metabolismo , Animais , Feminino , Gentamicinas/administração & dosagem , Gentamicinas/urina , Cinética , Ratos , Distribuição TecidualRESUMO
The significance of continuous intrarenal levels of gentamicin in the treatment of acute pyelonephritis due to Echerichia coli was investigated in rats. Treatment was started 24 hr after E. coli was injected into the left kidney. A single dose or three successive doses (10 mg/kg of body weight) of gentamicin administered ip every 8 hr could not sterilize the kidneys. Injections of gentamicin (10 mg/kg) every 12 hr for seven or 14 days resulted in continuous levels of the drug in the medulla that persisted above the minimal inhibitory concentration for E. coli (1.6 microgram/ml) for six months or more. Whereas greater than or equal to 73% of the right kidneys or urine specimens were found to be sterile up to six months following a week of therapy, only 23% of the left kidneys were sterile. Two weeks of treatment sterilized greater than or equal to 86% of the left kidneys, right kidneys, and urine specimens. Concentrations of drug in serum and urine were poor predictors of both the intrarenal distribution of drug and the outcome of pyelonephritis.