[Prospective considerations on the dose-effect relationship in antibiotic therapy].
Even though antibiotic in vivo and in vitro modes of action are not superposable, laboratory studies allow a logical approach to the treatment of infections. The answer to the question "What dose and for how long?" frequently asked during the treatment of a severe infection is not necessarily "The maximum dose for a long duration". The following points among many others, should be taken into consideration. The rate of bacterial action of beta-lactams on Gram negative bacilli is concentration dependent for ampicillin and amoxicillin for instance. This rate is hardly concentration dependent for ureidopenicillins (azlocillin, mezlocillin and piperacillin) and azthreonam which bind principally on PBP3. With third generation cephalosporins, in relation to concentrations, two steps in bactericidal rate may be observed. The post-antibiotic effect is often short (1 hour). The rate of bactericidal action of beta-lactams on Staphylococcus aureus is hardly concentration dependent. The post-antibiotic effect may be long (4 to 6 hours). A paradoxical effect may be observed namely with Streptococcus faecalis. The killing rate of beta-lactams is inoculum dependent. The aminoglycosides have a very high bactericidal activity rate on Gram positive and Gram negative bacteria. The post-antibiotic effect is long (4 to 6 hours). The antibacterial effect is little inoculum dependent. These conclusions are driven from experiences performed on cultures in growth phase. One of the controversial point related to the in vitro in vivo relationship is the ignorance of the multiplication rate of the bacteria in the infected site.(ABSTRACT TRUNCATED AT 250 WORDS)
Yourassowsky
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Département de Microbiologie, Hôpital universitaire Brugmann, Bruxelles, Belgique.
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007769:Lactams; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007769:Lactams
Considérations prospectives sur la relation dose-effet en thérapetique antibiotique.