Predicting the efficacy of antimicrobial agents in respiratory infections--is tissue concentration a valid measure?

Abstract

Despite methodological and interpretive problems associated with studies of antibiotic concentrations in tissues, it is important to confirm the presence of a drug in significant concentrations in tissues and fluids at a particular site. For antibiotics used in the treatment of community-acquired respiratory infections, tissue distribution at sites of potential infection in the respiratory tree has been related to clinical outcome. Measurement of antibiotic concentrations achieved in lung parenchyma epithelial lining fluid, bronchial mucosa or bronchial secretions has indicated significant levels for beta-lactams and macrolides. Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of macrolides, as shown in several models of phagocytic cells, and of intracellular antibacterial activities. For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactam and of macrolides should be of value. For bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides that can be achieved in extravascular and intracellular fluids should have clinical relevance, as shown in this review. Moreover with newer macrolides one may expect a better patient compliance due to prolonged persistence of drug in tissues and cells which results in shorter duration of treatment and once-daily dose administration. Finally, for some sites of infection and particularly in the human respiratory tree, there is a clear relationship between local concentrations and clinical efficacy.