par Yourassowsky, Eugène
Référence Annales de biologie clinique, 46, 2, page (138-143)
Publication Publié, 1988
Article révisé par les pairs
Résumé : 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 betalactams 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 postantibiotic effect is often short (1 hour). The rate of bactericidal action of betalactams on Staphylococcus aureus is hardly concentration dependent. The postantibiotic effect may be long (4 to 6 hours). A paradoxical effect may be observed namely with Streptococcus faecalis. The killing rate of betalactams is inoculum dependent. The aminoglycosides have a very high bactericidal activity rate on Gram positive and Gram negative bacteria. The postantibiotic 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 controversal point related to the in vitro in vivo relationship is the ignorance of the multiplication rate of the bacteria in the infected site. On the other hand betalactams are usually not very toxic compared to aminoglycosides, the therapeutical margin of which is narrow. Based on these data, one of the open perspectives of the treatment of severe infections would be: a betalactam (loading dose during 2 days following by a posology which determined a constant blood concentration close to MIC X 10; an aminoglycoside in one shot at a high dose, only the first day. The toxicity of a unique dose of aminoglycoside probably concerns only the muscular jonction but neither the kidney nor the cranial nerve VIII. This high dose of aminoglycoside would reduce the inoculum and should increase, therefore, the activity of the betalactam. The clinical relevance of these proposals still remains to be established.