[Evaluation of the posology of antibiotics]

The determination of the dose regimen of a new antibiotic is difficult because a dose/effect relationship cannot be established in patients with an infectious disease. The optimal dose is usually extrapolated from combined data provided by in vitro and in vivo microbiologic toxicologic and kinetic studies. Additional data ought to be produced in the future such as: kinetics of cidal effect in vitro, of the post antibiotic effect, of drug concentrations at the sit of infections itself, of the cidal serum activity in volunteers and patients; how these parameters are modified when modulating the mode of administration of the drug ought to be studied as well. The optimal dose, once it is roughly evaluated from classical studies, has to be adjusted: either by decreasing the dose, through an appropriate program of clinical trials with non-threatening life infections; or by increasing the dose in severe infections, through an in-depth analysis of new data available because of the improvement of: the design of clinical trials, the sensitivity of analytical techniques, the standardized serum bactericidal tests, the sophisticated monoparametric animal models simulating human infections, our knowledge of drugs mechanisms of toxicity. Establishing a rational dose regimen obviously requires a long-term multidisciplinary approach of the problem.