PHARMACOKINETICS OF GENTAMICIN IN THE TREATMENT OF RENAL INFECTION - THERAPEUTIC ANOMALY EXPLAINED

A model of pyelonephritis was used to investigate the ability of gentamicin to eradicate experimental renal infection. Escherichia coli pyelonephritis was induced in 56 rats, and treatment with gentamicin was started 7 days after challenge and was maintained for 11 days. Renal tissue examined at autopsy 14 days after the final dose of gentamicin was sterile on initial culture. Dilution of the homogenized preparations of renal tissue before culture revealed that substantial numbers of E. coli survived and up to 2.5 .times. 105 E. coli could be demonstrated in the kidney in this way. Bactericidal concentrations of gentamicin were demonstrated in the renal cortex up to 14 days after the final administration. Renal cortical tissue was sterile in 88% of the tissue examined, but bacterial persistence was found in the medulla (29% sterile) where the concentration of gentamicin was comparatively low. A reciprocal relationship between the site of bacterial persistence and the concentration of antimicrobial agent in the kidney indicates how infection of the renal parenchyma can be maintained despite the presence of an apparent overall bactericidal concentration of gentamicin. The importance of relating the pharmacokinetics of the antimicrobial agent and the bacteriologic features of the disease to local and anatomic characteristics of the kidney in the treatment of pyelonephritis is demonstrated.