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酮内酯类是半合成红霉素A衍生物 ,泰利霉素是这类药中第 1个批准用于临床的 ,ABC -773已进行Ⅲ期临床 ,其它酮内酯处于临床前研究阶段。酮内酯与 5 0S核糖体亚基的肽转移酶位点相互作用和 2 3SrRNA的结构域ⅡA75 2和结构域ⅤA2 0 5 8相互作用抑制细菌蛋白质合成。这些化合物也抑制核糖体 5 0S亚基形成 ,酮内酯对革兰氏阳性菌 (呼吸道感染包括耐青霉素和耐红霉素A的肺炎链球菌 )有良好活性。已公布泰利霉素 15项临床试验即 4项随机双盲比较试验、3项社区获得性肺炎的公开标记研究、3项慢性支气管炎急性恶化随机双盲试验、2项咽炎随机双盲试验、2项双盲比较试验和 1项急性上颌骨窦炎公开标记试验。所有试验临床应答率良好 ,肺炎链球菌菌血症和耐青霉素G和红霉素A肺炎链球菌感染的根除率至少与对照药相当。
Ketolides are semi-synthetic erythromycin A derivatives, telithromycin is the first of these drugs approved for clinical use, ABC -773 has been phase III clinical, and other ketolides in preclinical studies. The interaction of ketolipids with the peptidyl transferase site of the 50S ribosomal subunit and the interaction of domain IIA752 and domain VA2 0 58 of 23SrRNA inhibit bacterial protein synthesis. These compounds also inhibit the formation of the ribosomal 50s subunit, which has good activity against Gram-positive bacteria (respiratory infections including Streptococcus pneumoniae resistant to penicillin and erythromycin A). Four clinical trials of telithromycin, four randomized, double-blind trials, three open-label studies of community-acquired pneumonia, three randomized double-blind trials of chronic bronchitis, two randomized double-blind trials of pharyngitis, Double-blind comparison test and an open marking test of acute maxillary sinusitis. The clinical response rates were good in all trials with rates of eradication of pneumococcal bacteremia and penicillin-G and erythromycin-A-bearing pneumococcal infections at least comparable to those of the comparator.