[Methods for in vitro studies of antibiotic combinations. Indications and limits]

Several methods are available in the bacteriology laboratory to study the antibacterial effect of antibiotic combinations. With "end point" methods, results are read and interpreted after 18 or 24 hours of incubation. Amongst these methods, gel diffusion is technically easy but gives only qualitative results. Respective concentrations in the interaction zone cannot be evaluated and are unrelated to concentrations obtained in vivo. In liquid medium, the "checker board" method offers the possibility of combining a large number of concentrations. Interpretation may be graphic or mathematical. It is often arbitrary. But above all these methods fail to recognize events which occur during the 18 or 24 hours of incubation. Kinetic methods can be used to evaluate the kinetics of bactericidal action in relation to time and hence to compare the rapidity and degree of the bactericidal action of antibiotics used alone or in combination. However, only a limited number of concentrations can be studied. During the evaluation of a new antibiotic all methods must be tried to determine the possible synergistic or antagonistic effects of combinations regarding bacteria with known different resistance mechanisms. The broad outline thus obtained serves as a prescribing base for combinations. Bactericidal effect should be confirmed by a kinetic method where the concentrations in contact with the bacterial inoculum are selected in relation to presumed concentrations obtained at the site of infection.