Hoban D J
Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba, Canada.
J Chemother. 2002 Jul;14 Suppl 3:25-30. doi: 10.1080/1120009x.2002.11782349.
Resistance to macrolides is not a new phenomenon but it deserves attention because of the widespread use of these agents and their inclusion in many clinical guidelines for respiratory tract infections. The most common mechanisms by which Streptococcus pneumoniae and Streptococcus pyogenes develop resistance to macrolides is by target site modification (erythromycin ribosome methylase, erm) and efflux of the drug out of the organisms (macrolide efflux, mef). Target site modification may be of greater concern because it confers high-level resistance to all antimicrobials in the macrolide-lincosamide-streptograminB (MLSB) group. The genotype profiles of macrolide-resistant S. pneumoniae and S. pyogenes differ somewhat across regions in the US and between the US and Canada and other countries. There is some evidence for an association between macrolide resistance and treatment failure but this must be researched more fully. S. pneumoniae and S. pyogenes isolates resistant to macrolides are generally susceptible to ketolide antimicrobials because these agents bind more strongly to the relevant domain of the ribosomal subunit (withstanding erm resistance) and are less vulnerable to efflux compared to the macrolides.
对大环内酯类药物的耐药性并非新现象，但鉴于这些药物的广泛使用及其被纳入许多呼吸道感染临床指南中，这一现象值得关注。肺炎链球菌和化脓性链球菌对大环内酯类药物产生耐药性的最常见机制是靶点修饰（红霉素核糖体甲基化酶，erm）以及药物从菌体中流出（大环内酯类外排，mef）。靶点修饰可能更令人担忧，因为它赋予对大环内酯-林可酰胺-链阳菌素B（MLSB）组中所有抗菌药物的高水平耐药性。在美国，肺炎链球菌和化脓性链球菌大环内酯类耐药株的基因型谱在不同地区之间以及美国与加拿大和其他国家之间存在一定差异。有一些证据表明大环内酯类耐药性与治疗失败之间存在关联，但这一点必须进行更充分的研究。对大环内酯类药物耐药的肺炎链球菌和化脓性链球菌分离株通常对酮内酯类抗菌药物敏感，因为这些药物与核糖体亚基的相关结构域结合更紧密（可抵抗erm耐药性），并且与大环内酯类药物相比，更不易被外排。
