実験的腎盂腎炎における抗生剤の効果に関する研究

Abstract

It has been proved that the experimental pyelonephritis can be produced in rabbits by inoculation of E. coli, Proteus mirabilis and Pseudomonas which were isolated from the patients of urinarv tract infections to the unilaterally incompletelv obstructed ureter in a preliminary study. So, evaluation of the effectiveness of antibiotics given was attempted with using the in vivo technic. Studies were performed in two groups according to antimicrobial dosage. Antimicrobials were given immediately after the bacterial inoculation with one shot in prophylaxy group, while the drugs were administered daily for a week following the inoculation in treatment group. Correlation between the in vivo effectiveness of the drugs and serum, urine and kidney levels were also examined. The results obtained were as follows: 1. No significant difference of mortality ratio in the experimental animals among control, prophylaxy and treatment group was observed despite the kinds of bacterias inoculated. 2. Pyelonephritis was experimentally produced in 68 of 72 animals with average of 94.4%, but no meaningful difference was found in the occurrence among three kinds of bacterial strains. 3. As there was no specific difference in histopathological findings among the produced experimental pyelonephritis in rabbits. it is considered that these strains may be similar as far as the pathogenicities or virulence to rabbit's kidney is concerned. 4. The drugs were arranged in order of the effectiveness in the prophlaxy group: KM=TP>DOTC=AKM>TC=CP in E. coli infected group. GM=KM=CB-PC>AKM=TP=CP>DOTC=TC=CL=PL-B in Proteus group and CL>GM>PL-B>CP in Pseudomonas group. 5. The effectiveness of the drugs in treatment group was also arranged in order; KM>AKM>DOTC>TC=CP in E. coli group, KM>AKM>TP=DOTC in Proteus group and CL>GM>PL-B=CP in Pseudomonas group. 6. It is likely necessary to obtain higher serum levels and more than 10 times higher urine levels than MIC for the sufficient prophylaxv with one shot administration of the drugs. Histopathological improvement in E. coli infected kidney in the treatment group would be derived from higher mine levels of the drugs more than 6 times than MIC. 7. Higher urine levels more than 2.5 times than MIC may also be needed for the sufl1cienl prophylactic and therapeutic effect in Proteus group. So that GM and CB-PC whose mine levels reached 50 times higher than MIC with higher serum levels than MIC are thought to be prophylactic. 8. Satisfactory prophylactic and therapeutic effect were expected in Pseudomonas inoculated animals with administration of CL whose urine levels recorded 51 times higher than MIC with higher serum levels than MIC. However, neither CB-PC nor GM did show sufficient effect as ratios of their urine levels against MIC were lower than CL. 9. As far as evaluation of the effectiveness of antibiotics in the experimental pyelonephritis is concerned, close correlation was found not to serum levels but to urine levels. In order to obtain excellent results in E. coli and Proteus induced pyelonephritis in the animals, drug concentration in the urine should be more than 10 times higher than MIC, while more than 50 times urine levels seemed to be required in the Pseudomonas induced pyelonephritis. 10. It was convinced that a bactericidal drug is more effective than a bacteriostatic agent. 11. The experimental pyelonephritis may be an excellent model for the evaluation of chemotherapeutic effect in vivo to examine bacteriological and histopathological findings because the technic is so simple that the result can be evaluated easily and objectively. 12. It was impressed that chemotherapeutic effect was satisfactory even in the existence of a predisposing factor or complication in the urinary tracts.