AN EXPERIMENTAL CHEMOTHERAPY ON PYELONEPHRITIS IN RABBITS INOCULATED WITH ESCHERICHIA COLI

Abstract

In order to evaluate an appropriate chemotherapy on acute pyelonephritis and protection of the occurrence of chronic pyelonephritis, studies have been performed with experimental pyelonephritis in rabbits inoculated with E. coli NIHJ-JC 2. Ampicillin was chosen for the study and it was given to animal with various dosage. The drug levels in serum, urine and renal tissue in normal and pyelonephritic animals were measured by thin layer cup method. Animals were sacrificed one month after the bacterial inoculation and studied bacteriologically and histopathologically. The results obtained were as follows.
1. Serum levels in the normal rabbits one hour after intramuscular injection of 20 mg/kg of ampicillin ranged 15.8μg/ml, however, the serum levels obtained 3 hours later were less than MIC of the bacterial strain. Total recovery of the drug into the urine up to 5 hours marked 45%. Dose response of the serum level following i. m. administration of 100 mg/kg of the drug was proved one hour later and the serum level was kept higher than MIC even 3 hours later.
2. Early stage of inflammation in the kidney was observed 24 hours after the inoculation and acute pyelonephritis seemed to be established 48 hours later clinicopathologically. Pyelonephritic change was obviously observed 72 hours later. Severe pyelonephritic change associated with formation of diffuse microabscesses was completed one week later and findings of chronic pyelonephritis were found histopathologically one month later.
3. The more the pyelonephritic change progressed in the histopathology, the less the drug level was in the kidney, both cortex and medulla, although no significant differences of the drug level were proved in the serum and the bladder urine between the unilateral pyelonephritic and normal animals. Dose response of the drug level in the affected kidney was no longer proved in the animals given 20 and 100 mg/kg of the drug one week after the bacterial inoculation. However, the drug level in the affected kidney exceeded MIC of the inoculated bacterial strain with the administration of both 20 and 100 mg/kg of the drug.
4. No evidence of histopathological efficacies was proved in the animals treated by 20 mg/kg of ampicillin started from 48 and 72 hours after the inoculation. Enhancement of in vivo effect was studied a little in animals with combined regimen of glycyrrhizine, lysozyme and γ-globulin. Sufficient histopathological effect was observed in the animals treated by 40 mg/kg of ampicillin started from 48 hours after the inoculation as same as in the animals treated by 100 mg/kg of the drug. In the animal group treatment started from 72 hours with a dose of 40 mg/kg of ampicillin, the result was somewhat inferior to the above group. Furthermore, no histopathological response was found in animals treated by even 100 mg/kg of the drug started from one week after the inoculation. These results indicated that a large dose of chemotherapy is not always necessary in the treatment of early stage of acute pyelonephritis.
5. Histopathological findings of chronic pyelonephritis were predominantly observed one month later in the animals regardless of chemotherapeutic response. Hence the occurrence of chronic pyelonephritis in rabbits may develop in an existence of the ureteric stenosis associated with immunological response, in spite of the chemotherapeutic effect.