Carbon C, Poole M D
Service de Medecine Interne, Institut National de la Sante et Recherche Medical, Hopital Bichat - Claude Bernard, Paris, France.
J Chemother. 1999 Apr;11(2):107-18. doi: 10.1179/joc.1999.11.2.107.
The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infection (RTI). The newer agents clarithromycin and azithromycin are frequently prescribed as first- or second-line therapy, and have been considered as superior to erythromycin in microbiological activity and clinical efficacy. In-vitro data show that clarithromycin and azithromycin have good activity (MIC < or = 0.5 microg/ml) against certain RTI pathogens. However the activity of both compounds is intrinsically low against Haemophilus influenzae whilst several other important RTI pathogens - notably Streptococcus pneumoniae and Streptococcus pyogenes - exhibit a high prevalence of resistance to them. In many countries, the prevalence of resistance to clarithromycin and azithromycin is still rising with cross resistance with erythromycin. Maximum serum concentrations of clarithromycin and azithromycin are lower than the MIC90s for these agents against H. influenzae and S. pneumoniae. Concentrations in tissues have been reported to be much higher than those in serum. However, the high concentrations observed in tissues are largely a reflection of high concentrations inside cells. Concentrations of clarithromycin and azithromycin in extracellular tissue fluids, where Haemophilus and streptococci are located, are in equilibrium with concentrations in the serum, and remain low. It has been suggested that phagocytes deliver azithromycin to infection sites in a targeted fashion, but the evidence in support of this hypothesis is weak. Recent clinical experience with clarithromycin and azithromycin is consistent with preclinical results, and suggests that these agents have limited efficacy against certain respiratory infections. Clarithromycin and azithromycin are the first choice treatment of atypical infections caused by intracellular pathogens. For community-acquired RTIs, where H. influenzae and S. pneumoniae are present, they may no longer be an appropriate choice for first-line therapy. Indeed, in areas where levels of drug resistant S. pneumoniae are high, their use may be questionable as second-line therapy.
大环内酯类抗生素已被广泛应用，常用于治疗社区获得性呼吸道感染（RTI）。新型药物克拉霉素和阿奇霉素常被作为一线或二线治疗药物，在微生物活性和临床疗效方面被认为优于红霉素。体外数据显示，克拉霉素和阿奇霉素对某些RTI病原体具有良好活性（MIC≤0.5μg/ml）。然而，这两种化合物对流感嗜血杆菌的活性本质上较低，而其他几种重要的RTI病原体——尤其是肺炎链球菌和化脓性链球菌——对它们的耐药率很高。在许多国家，对克拉霉素和阿奇霉素的耐药率仍在上升，且与红霉素存在交叉耐药。克拉霉素和阿奇霉素的血清最大浓度低于它们针对流感嗜血杆菌和肺炎链球菌的MIC90值。据报道，组织中的浓度远高于血清中的浓度。然而，在组织中观察到的高浓度很大程度上反映了细胞内的高浓度。克拉霉素和阿奇霉素在细胞外组织液（流感嗜血杆菌和链球菌所在部位）中的浓度与血清中的浓度处于平衡状态，且仍然较低。有人提出吞噬细胞以靶向方式将阿奇霉素输送到感染部位，但支持这一假设的证据不足。克拉霉素和阿奇霉素的近期临床经验与临床前结果一致，表明这些药物对某些呼吸道感染的疗效有限。克拉霉素和阿奇霉素是由细胞内病原体引起的非典型感染的首选治疗药物。对于存在流感嗜血杆菌和肺炎链球菌的社区获得性RTIs，它们可能不再是一线治疗的合适选择。事实上，在肺炎链球菌耐药水平较高的地区，将其作为二线治疗药物使用可能存在疑问。
