Bergogne-Bérézin E
Microbiology Department-Bichat-Claude Bernard University Hospital, Paris, France.
J Antimicrob Chemother. 1995 Mar;35(3):363-71. doi: 10.1093/jac/35.3.363.
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.
尽管与组织中抗生素浓度研究相关的方法学和解释性问题存在，但确认药物在特定部位的组织和体液中以显著浓度存在很重要。对于用于治疗社区获得性呼吸道感染的抗生素，呼吸道树潜在感染部位的组织分布与临床结果相关。对肺实质上皮衬液、支气管黏膜或支气管分泌物中抗生素浓度的测量表明，β-内酰胺类和大环内酯类药物达到了显著水平。许多呼吸道感染由专性或兼性细胞内病原体引起，在几种吞噬细胞模型以及细胞内抗菌活性模型中显示，大环内酯类药物的细胞内渗透和积累可能会根除这些病原体。对于位于肺细胞外部位的细菌感染，了解β-内酰胺类和大环内酯类药物可达到的浓度应具有重要意义。对于在肺泡巨噬细胞中繁殖的细菌，如本综述所示，在血管外和细胞内液中可达到的新大环内酯类药物的高浓度应具有临床相关性。此外，对于更新的大环内酯类药物，由于药物在组织和细胞中的持续时间延长，从而导致治疗时间缩短和每日一次给药，人们可能期望患者有更好的依从性。最后，对于某些感染部位，尤其是在人类呼吸道树中，局部浓度与临床疗效之间存在明确的关系。
