A STUDY OF CHEMOTHERAPY ON EXPERIMENTAL PYELONEPHRITIS IN RABBITS INOCULATED WITH PSEUDOMONAS AERUGINOSA

Abstract

It is well recognized that urinary tract infection caused by Pseudomonas aeruginosa is difficult to treat and manage because of the drug resistance and an existence of urinary stream disturbance in such cases. So that a large dose chemotherapy using such as carbenicillin (CBPC) and sulbenicillin (SBPC) against Pseudomonas infections is used to be applied recently. In order to evaluate an appropriate chemotherapy for Pseudomonas infections in the urinary tracts, especilly pyelonephritis, the following studies have been performed on experimental pyelonephritis in rabbits.
1. MICs and MBCs of CBPC and gentamicin (GM) against Pseudomonas aeruginosa NCTC 10490 (standard strain) and Pseudomonas aeruginosa isolated from urinary tract infections (UTI strain) were measured by agar dilution method and by SILVERBLATT & TURCK's method. It was proved that the difference between MIC and MBC of the drugs against the bacterias ranged from twice to 16 times.
2. Experimental pyelonephritis in rabbits was produced by inoculation with both strains of Pseudomonas aeruginosa into unilaterally obstructed ureter. The animals were sacrificed 24, 48, 72 hours and a week after the inoculation. Occurrence of acute pyelonephritis in rabbits was proved 48 hours after the inoculation from histopathological and bacteriological points of view.
3. Concentration of CBPC and GM in the serum, urine and renal tissue 1, 3, 5 hours after the intramuscular administration in acute pyelonephritic rabbits was measured by thin layer cup method. It was suggested that tissue level of the drugs in acute pyelonephritic kidney was recorded higher and decreased more gradually than that in the normal kidney.
4. The animals 48 hours previously inoculated with the bacterial strains were treated by intramuscular injection of CBPC or GM once a day for 7 days. Doses of the drugs were 40, 200, 400 mg per kg for CBPC and 1. 6, 8. 0, 16 mg per kg for GM. The animals were sacrificed on next day of the cessation of the treatment. Histopathological findings demonstrated complete healing in rabbits treated by CBPC showing dose response. However, dose response was not reflected and consequently the results were poor in efficacy in UTI strain inoculated animals treated by GM, while good to excellent results were obtained in standard strain inoculated animals.
5. The fact came into the light the tissue level of the drugs in the pyelonephritic kidney revealed higher than MBC in rabbits who obtained perfect histopathological and bacteriological healing. MBC is thought to be more important than MIC for a marker of the treatment of acute pyelonephritis induced by Pseudomonas aeruginosa.
6. OEP-HA titer was measured in 10 normal rabbits and in 3 rabbits inoculated with standard strain of Pseudomonas aeruginosa but not medicated. OEP-HA reagent was supplied by Prof. HOMMA of the Institute of Medical Science, the University of Tokyo. Microtiter method was applied. OEPHA titer showed lower than 40 × in normal controls. On the other hand, it began to rise 24 hours after the bacterial inoculation and reached range from 160 to 320 ×. Elevation of OEP-HA titer was kept for 6 months after, the inoculation. Measurement of OEP-HA titer is useful for diagnosis of Pseudomonas aeruginosa infection in the urinary tract.