Chu D T
Kosan Biosciences, Inc., Hayward, California 94545, USA.
Med Res Rev. 1999 Nov;19(6):497-520. doi: 10.1002/(sici)1098-1128(199911)19:6<497::aid-med3>3.0.co;2-r.
Macrolides, such as clarithromycin and azithromycin, having good activity against pathogens such as Legionella, Chlamydia, Campylobacter spp, Branhamella spp, Pasteurella multocida and streptococci, have gained wide acceptance for the treatment of both upper and lower respiratory tracts, as well as cutaneous infections. Emergence of bacterial resistance, particularly in gram-positive bacteria, has been observed. Macrolide-resistant Streptococcus pneumoniae and S. pyogenes are found in France and many other countries, resulting in failure of therapy for pneumonia, pharyngitis, and skin infection. RU 004, HMR 3647, and TE 802 were reported to be active against these resistant strains. Research at Abbott produced several macrolide derivatives in the anhydrolide, tricyclic and tetracyclic ketolides as well as 6-O-alkyl ketolides series having potent activity against macrolide resistant S. pyogenes and S. pneumoniae. Research on streptogramins to overcome bacterial resistance in gram-positive bacteria has produced interesting compounds. Another class of antibacterial agent called quinolones is useful for the treatment of bacterial infections of respiratory tract, urinary tract, skin and soft tissues, as well as sexually transmitted diseases. Ciprofloxacin, the market leader, however, has low potency against anaerobes. Bacterial resistance ( such as Pseudomonas aeruginosa and methicillin- resistant Staphylococcus aureus ) to ciprofloxacin is increasing rapidly. Many quinolone compounds are being synthesized to address these drawbacks. The new quinolones currently under development are characterized by enhanced activities against streptococci, staphylococci, enterococci, and anaerobes. This presentation reviews the current research in the identification of agents to overcome the macrolide and quinolone resistance.
大环内酯类药物，如克拉霉素和阿奇霉素，对嗜肺军团菌、衣原体、弯曲菌属、布兰汉菌属、多杀巴斯德菌和链球菌等病原体具有良好活性，已被广泛用于治疗上、下呼吸道感染以及皮肤感染。已观察到细菌耐药性的出现，尤其是在革兰氏阳性菌中。在法国和许多其他国家发现了对大环内酯类耐药的肺炎链球菌和化脓性链球菌，导致肺炎、咽炎和皮肤感染的治疗失败。据报道，RU 004、HMR 3647和TE 802对这些耐药菌株有活性。雅培公司的研究生产了几种大环内酯衍生物，包括内酯、三环和四环酮内酯以及6 - O -烷基酮内酯系列，它们对耐大环内酯类的化脓性链球菌和肺炎链球菌具有强效活性。关于链阳菌素以克服革兰氏阳性菌耐药性的研究产生了一些有趣的化合物。另一类称为喹诺酮类的抗菌剂可用于治疗呼吸道、泌尿道、皮肤和软组织的细菌感染以及性传播疾病。然而，市场领先的环丙沙星对厌氧菌的活性较低。细菌（如铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌）对环丙沙星的耐药性正在迅速增加。正在合成许多喹诺酮类化合物以解决这些缺点。目前正在研发的新型喹诺酮类药物的特点是对链球菌、葡萄球菌、肠球菌和厌氧菌的活性增强。本报告综述了目前在鉴定克服大环内酯类和喹诺酮类耐药性药物方面的研究。
