喹奴普丁-达福普汀治疗多重耐药革兰阳性细菌感染的研究进展

Treatment Progress of Multidrug-resistant Gram-positive Bacteria-associated Infections with Quinupristin/Dalfopristin

喹奴普丁-达福普汀是第一个经静脉给药的水溶性、半合成链阳性菌素(streptogramin)衍生物,其2种有效成分以30:70的比例混合,分别应用时只有抑菌作用,联合应用则有协同杀菌作用。该品对大多数革兰阳性细菌具有杀菌活性,对屎肠球菌只有抑菌作用。喹奴普丁和达福普汀分别与细菌50S核糖体亚单位23S RNA的不同部位结合,通过抑制细菌蛋白质合成而发挥抗菌作用。目前FDA仅批准该药用于治疗成人严重或致命性耐万古霉素屎肠球菌菌血症相关性感染、甲氧西林敏感性金黄色葡萄球菌及A组酿脓链球菌引起的皮肤及皮肤组织感染。儿童应用喹奴普丁-达福普汀的安全性及疗效尚未被充分证实。该药的主要不良反应为静脉刺激与肌痛/关节痛。虽然喹奴普丁-达福普汀不经肝脏细胞色素P450酶代谢,但其却是CYP 3A4酶抑制剂,与经过CYP 3A4代谢的药物合用时可发生明显的药动学相互作用,导致这些药物的血浆浓度升高。

Quinupristin/dalfopristin, composed of two water-soluble semi-synthetic derivatives of pristinamycin in a 30：70 ratio, is the first marketed intravenous injection drug of streptogramin antibiotics with the synergistically bactericidal potency against the most gram-positive bacteria, except Enterococcus faecium to which they usually show bacteriostasis. Both dalfopristin and quinupristin inhibit bacterial protein synthesis by binding to different sites on bacterial 50S ribosomal subunit. Quinupristin/dalfopristin has been approved by the US Food and Drug Administration （FDA） for the treatment of the adults with serious or life-threatening bacteremia infections associated with vancomycin-resistant E. faecium （VREF） and skin and skin-structure infections caused by meticillin-susceptible S. aureus （MSSA） and Streptococcus pyogenes. The safety and efficacy of quinupristin/dalfopristin have not been well confirmed in children. Its major toxicities include venous irritation and arthralgias or myalgias. Although quinupristin and dalfopristin are not metabolised via cytochrome P450 （CYP） enzymes, they are inhibitors of CYP3A4. Concomitant administration of quinupristin/dalfopristin with medications metabolised via CYP3A4 significantly alter the pharmacokinetic profile of the latter.