抗菌剤の投与方法に関する研究 : 投与形式の試験管内実験による検討

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Concerning the administration schedule of penicillin, Eagle et al. reported that "penicillin time" was important against gram-positive coccal infections in 1940's and 1950's. Since then, many antimicrobial agents having different antibacterial mechanism from penicillin were discovered and the administration schedule of those drugs were established theoretically in relation to the serum concentration and minimal inhibitory concentration (MIC) against infecting organisms. The theoretical schedule were not always kept in practice. Neverthless, fairly good clinical effects were obstained. On the other hand, massive dose therapy with penicillins and cephalosporins became popular recently, but the laboratory or fundamental experiments were not sufficiently performed. Therefore, basic experiments were carried out in order to reexamine the wasteless and effective dosage schedule of antibitotics. In order to compare the growth inhibition periods, E. coli was exposed to the following antibiotics for varying periods and/or varying concentrations. The antibiotics used were ampicillin (ABPC), sulbenicillin (SBPC) and carbenicillin (CBPC) as penicillins, cephalothin (CEP) as cephalosporins and kanamycin (KM) as aminoglycosides. The test organisms were E. coli (NIHJ JC-2) as the standard strain and E. coli (4897) as the clinical strain. To limit the exposure period within a specific short time, antibiotics were inactivated by penicillinase, cephalosporinase and KM inactivating crude cell-free extract made by the author from KM resistant E. coli. Bacterial growth curves were observed mostly with biophotometer. In the case in whom drug exposure period was limited to a specific short time, i.e. 3 or 6 hours which are practicable in a clinical use, E. coli could not be killed completely even if the organisms were exposed to considerably high concentrations of those drugs and even if logarithmically growing organisms were used. This fact suggests that host defence mechanism is indispensable to get complete killing of the infecting organisms in the focus. In the viewpoint of host defence mechanism, bacterial growth inhibition period is considered to be important. When E. coli was exposed to penicillins or CET for 3 hours, the growth inhibition periods were barely elongated in spite of the elevation of antibiotic concentrations, but in the case of KM, the growth inhibition periods were elongated with elevation of KM concentrations from 1/2 MIC to 4 MIC. There was some difference in bacterial growth inhibition effects between penicillinscephalosporins and aminoglycosides effects. On the other hand, an interesting problem is which is better to use "high concentration of drugs for short time" or "low concentration over a long time". It was revealed better to expose for a long time or expose multiply even to low concentration of drugs, rather than to expose to high concentration of drugs for a short period or expose one time in the case of penicillins and cephalosporins. However, in the case of KM, nearly the same growth inhibition periods were obtained by both of the different exposure models. The author thinks that KM has the potential to lengthen the intervals between dosages with elevation of its concentrations. In summary, these facts suggest that penicillins and cephalosporins should be scheduled differently from aminoglycosides.
社団法人日本泌尿器科学会の論文
1978-11-20

抗菌剤の投与方法に関する研究 : 投与形式の試験管内実験による検討

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