New concepts in the pulmonary disposition of antibiotics.

Despite interpretive problems associated with studies of antibiotic concentrations in tissues, it is of major interest to correlate the presence of the drug at significant concentrations in lung tissues and fluids at a particular site with its clinical efficacy. All the models described above have their uses as well as their limitations. Measurement of antibiotic concentrations achieved in lung parenchyma, ELF, bronchial mucosa of bronchial secretions has shown variable levels for the same drug. Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of quinolones, of macrolides, as shown in several models of phagocytic cells, and as a result of intracellular antibacterial activities. For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactams, of aminoglycosides, of quinolones should be of value, whereas for bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides or new fluoroquinolones that can be achieved in extravascular and intracellular fluids should have clinical relevance. Animal models of severe pneumonia, as well as studies in patients hospitalized in intensive care units, have provided correlation between clinical outcomes and high lung tissue and intramacrophagic concentrations of fluoroquinolones, or of macrolides in legionellosis, or of ceftazidime or imipenem in pseudomonal pneumonia.