Braga P C
Department of Pharmacology, School of Medicine, University of Milan, Italy.
J Chemother. 2002 Apr;14(2):115-31. doi: 10.1179/joc.2002.14.2.115.
Rokitamycin is the latest semi-synthetic 16-membered ring macrolide introduced into clinical practice. It is characterized by greater hydrophobicity, better bacterial uptake and a slower release, more cohesive ribosomal binding, and a longer post-antibiotic-effect (PAE) than can be observed with other available 14-, 15- and 16-membered ring macrolides. Rokitamycin exerts its activity on strains that harbor inducible erm genes or the efflux gene, mef(A). It has also been reported to be more active in vitro than other 16-membered ring macrolides. However, these recognized features are not fully exploited yet because current automated test procedures used in many microbiological laboratories determine susceptibility only to erythromycin or clarithromycin. Resistance to 16-membered ring macrolides cannot be predicted solely on the basis of known resistance to erythromycin or clarithromycin as revealed by an automated susceptibility assay. At least equally important is the knowledge of the bacterial resistance phenotype. This is underlined by the existence of Gram-positive coccal strains resistant to erythromycin and other 14-,15-membered ring macrolides but susceptible to 16-membered ring macrolides. Since the local prevalence of erythromycin phenotypes is generally unknown but might determine the outcome of treatment, the procedure for identifying the phenotypes in erythromycin-resistant strains (which can be easily and cheaply performed using the two- or three-disk assay) should become routine, at least in the countries in which 16-membered ring macrolides are used. This approach should help to optimize the use of macrolides, improve our knowledge of the local prevalence of phenotypes resistant to erythromycin, and offer the possibility of treating infections caused by certain types of erythromycin-resistant pathogens.
罗他霉素是引入临床实践的最新半合成16元环大环内酯类抗生素。其特点是疏水性更强、细菌摄取更好、释放更慢、核糖体结合更紧密,且抗生素后效应(PAE)比其他现有的14元、15元和16元环大环内酯类抗生素更长。罗他霉素对携带诱导型erm基因或外排基因mef(A)的菌株具有活性。据报道,它在体外也比其他16元环大环内酯类抗生素更具活性。然而,这些公认的特性尚未得到充分利用,因为许多微生物实验室目前使用的自动化检测程序仅能确定对红霉素或克拉霉素的敏感性。不能仅根据自动化药敏试验显示的对红霉素或克拉霉素的已知耐药性来预测对16元环大环内酯类抗生素的耐药性。细菌耐药表型的了解至少同样重要。对红霉素和其他14元、15元环大环内酯类抗生素耐药但对16元环大环内酯类抗生素敏感的革兰氏阳性球菌菌株的存在就强调了这一点。由于红霉素表型的局部流行率通常未知,但可能决定治疗结果,因此在耐红霉素菌株中鉴定表型的程序(使用双盘或三盘试验可以轻松且廉价地进行)至少在使用16元环大环内酯类抗生素的国家应成为常规操作。这种方法应有助于优化大环内酯类抗生素的使用,增进我们对耐红霉素表型局部流行率的了解,并为治疗某些类型耐红霉素病原体引起的感染提供可能性。