Allington D R, Rivey M P
School of Pharmacy and Allied Health Sciences, University of Montana, Missoula 59812-1522, USA.
Clin Ther. 2001 Jan;23(1):24-44. doi: 10.1016/s0149-2918(01)80028-x.
The proliferation of multidrug-resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium (VREF), has created a pressing need for effective alternative antibiotics. Quinupristin/dalfopristin is a new combination streptogramin product with a selective spectrum of antibacterial activity, mainly against gram-positive aerobic bacteria. It has been assessed primarily in emergency-use protocols, in hospitalized patients with skin and skin-structure infections, and in patients with VREF bacteremia.
The objectives of this review were to summarize important results of in vitro microbiologic studies; to provide information on relevant pharmacokinetic parameters, drug interactions, and Y-site compatibility; and to assess efficacy and safety data from clinical studies of quinupristin/dalfopristin.
Articles included in this review were identified by a MEDLINE search of the literature published between 1966 and September 2000 using the terms Synercid, quinupristin, and dalfopristin. Additional articles were retrieved from the reference lists of articles identified in the MEDLINE search.
In vitro analysis of the spectrum of activity of quinupristin/dalfopristin has confirmed its relatively selective coverage of gram-positive aerobic bacteria. Both quinupristin and dalfopristin undergo hepatic metabolism and are extensively excreted in the feces. Combination quinupristin/dalfopristin inhibits the cytochrome P450 3A4 pathway, and caution is warranted with concomitant use of other medications eliminated via this pathway. In trials in patients with VREF infections, treatment success with quinupristin/dalfopristin varied depending on the site of infection, ranging from 51.9% in bacteremia of unknown origin to 88.9% in urinary tract infections. The results of comparative clinical trials suggest that quinupristin/dalfopristin has similar efficacy to that of commonly used antibiotics, including cefazolin, oxacillin, and vancomycin, in patients with skin and skin-structure infections or nosocomial pneumonia. The most frequently reported adverse effects with administration of quinupristin/dalfopristin were infusion-site inflammation, pain, and edema; other infusion-site reactions; and thrombophlebitis. Arthralgia, myalgia, nausea, diarrhea, vomiting, and rash occurred in 2.5% to 4.6% of patients and were the most frequently reported systemic adverse events.
Outcomes data from clinical trials indicate that quinupristin/dalfopristin has the potential to play an important role in the treatment of bacteremia, complicated skin and skin-structure infections, and nosocomial pneumonia caused by VREF. Issues of bacterial resistance to quinupristin/dalfopristin and other appropriate uses of this combination agent remain to be elucidated.
包括耐甲氧西林金黄色葡萄球菌和耐万古霉素屎肠球菌（VREF）在内的多重耐药革兰氏阳性菌的扩散，使得迫切需要有效的替代抗生素。奎奴普丁/达福普汀是一种新型链阳菌素组合产品，具有选择性抗菌活性谱，主要针对革兰氏阳性需氧菌。它主要在紧急使用方案中、患有皮肤及皮肤结构感染的住院患者以及患有VREF菌血症的患者中进行了评估。
本综述的目的是总结体外微生物学研究的重要结果；提供有关相关药代动力学参数、药物相互作用和Y位配伍性的信息；并评估奎奴普丁/达福普汀临床研究的疗效和安全性数据。
本综述纳入的文章通过对1966年至2000年9月发表的文献进行MEDLINE检索确定，检索词为Synercid、奎奴普丁和达福普汀。从MEDLINE检索中确定的文章的参考文献列表中检索其他文章。
对奎奴普丁/达福普汀活性谱的体外分析证实了其对革兰氏阳性需氧菌的相对选择性覆盖。奎奴普丁和达福普汀均经过肝脏代谢，并大量经粪便排泄。奎奴普丁/达福普汀组合抑制细胞色素P450 3A4途径，同时使用经该途径消除的其他药物时需谨慎。在VREF感染患者的试验中，奎奴普丁/达福普汀的治疗成功率因感染部位而异，从未知来源菌血症的51.9%到尿路感染的88.9%不等。比较临床试验的结果表明，在患有皮肤及皮肤结构感染或医院获得性肺炎的患者中，奎奴普丁/达福普汀与常用抗生素（包括头孢唑林、苯唑西林和万古霉素）的疗效相似。使用奎奴普丁/达福普汀最常报告的不良反应是输注部位炎症、疼痛和水肿；其他输注部位反应；以及血栓性静脉炎。关节痛、肌痛、恶心、腹泻、呕吐和皮疹发生在2.5%至4.6%的患者中，是最常报告的全身性不良事件。
临床试验的结果数据表明，奎奴普丁/达福普汀在治疗由VREF引起的菌血症、复杂性皮肤及皮肤结构感染和医院获得性肺炎方面有发挥重要作用的潜力。对奎奴普丁/达福普汀的细菌耐药性问题及该组合药物的其他适当用途仍有待阐明。
