Diffusion pulmonaire des céphalosporines de troisième génération : perfusion continue versus administration intermittente

Studies on tissue concentrations in the respiratory tree have been considered controversial due to non reliable techniques, ethical rules, costs of studies. Coming back to the concept of tissue distribution with new approaches based on more recent pharmacologic studies, antibiotic concentrations in the respiratory tree, have been studied in respiratory tissues and fluids, in severe respiratory infections: a relatively easy access to sampling in different parts of the RT has permitted the development of reliable studies of kinetics in man: this has resulted in new approaches to establish pharmacokinetic/pharmacodynamic parameters, and reliable bases for the modes of antibiotic administration in patients. The bactericidal activity of β-lactam antibiotics is mostly time-dependent, i.e. correlated to the time during which the antibiotic concentration is greater than the minimal inhibitory concentration (T>MIC) of the involved pathogen. To be efficacious at the site of infection, antibiotics must exhibit adequate tissue concentrations; therefore the knowledge of antibiotic tissue distribution is necessary in order to optimize therapeutic efficacy. Third-generation cephalosporins are β-lactam antibiotics widely used in the treatment of severe lung infections. The intrapulmonary diffusion of third-generation cephalosporins administered by continuous or intermittent infusion has been evaluated in several studies reporting various results. It has been suggested that the administration of these antimicrobials by continuous infusion appears to optimize their pharmacokinetic/pharmacodynamic profile by providing a T>MIC of 100% at the site of infection. However, to date, the superiority of continuous versus intermittent administration in terms of clinical efficacy has still not been demonstrated. Further rigorous clinical studies performed on a great number of patients may provide useful data.