Renal pharmacokinetic changes of gentamicin during enterococcal pyelonephritis

In the present study, the renal pharmacokinetics of gentamicin was investigated in pyelonephritic rats infected with Streptococcus (Enterococcus) faecalis. Four days after the induction of infection, animals were given either a single dose of gentamicin or two daily injections for 7 days. The treated animals were evaluated from 1 h to 6 months posttreatment. After a single injection, limited pharmacokinetic variations were observed, whereas after 14 injections infected kidneys demonstrated significantly higher concentrations and a more extended renal elimination phase of the antibiotic. Analysis of the area under the curve of the concentration in kidney versus time showed more marked renal accumulation by the infected and long-term treated animals than by normal animals or those receiving only one injection of aminoglycoside. Renal function remained normal in both the infected and normal animals treated with this aminoglycoside. These results demonstrate that S. faecalis pyelonephritis disturbs the renal handling of gentamicin and may increase the susceptibility of the kidney to aminoglycosides.