Lamb H M, Figgitt D P, Faulds D
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 1999 Dec;58(6):1061-97. doi: 10.2165/00003495-199958060-00008.
Quinupristin/dalfopristin is the first parenteral streptogramin antibacterial agent, and is a 30:70 (w/w) ratio of 2 semisynthetic pristinamycin derivatives. The combination has inhibitory activity against a broad range of gram-positive bacteria including methicillin-resistant staphylococci, vancomycin-resistant Enterococcus faecium (VREF), drug-resistant Streptococcus pneumoniae, other streptococci, Clostridium perfringens and Peptostreptococcus spp. The combination also has good activity against selected gram-negative respiratory tract pathogens including Moraxella catarrhalis, Legioniella pneumophila and Mycoplasma pneumoniae. Quinupristin/dalfopristin has poor activity against E. faecalis. The combination is bactericidal against staphylococci and streptococci, although constitutive erythromycin resistance can affect its activity. As for many other agents, quinupristin/dalfopristin is generally bacteriostatic against E. faecium. In patients with methicillin-resistant S. aureus (MRSA) or VREF infections participating in prospective emergency-use trials, quinupristin/dalfopristin 7.5 mg/kg every 8 or 12 hours achieved clinical or bacteriological success in > or =64% of patients. Emergence of resistance to quinupristin/dalfopristin was uncommon (4% of patients) in those with VREF infections. Quinupristin/dalfopristin 7.5 mg/kg 8- or 12-hourly also achieved similar clinical success rates to comparator agents in patients with presumed gram-positive complicated skin and skin structure infections or nosocomial pneumonia (administered in combination with aztreoman) in 3 large multicentre randomised trials. Systemic adverse events associated with quinupristin/dalfopristin include gastrointestinal events (nausea, vomiting and diarrhoea), rash and pruritus. Myalgias and arthralgias also occur at an overall incidence of 1.3%, although higher rates (2.5 to 31%) have been reported in patients with multiple comorbidities. Venous events are common if the drug is administered via a peripheral line; however, several management options (e.g. use of central venous access, increased infusion volume) may help to minimise their occurrence. Hyperbilirubinaemia has been documented in 3.1% of quinupristin/dalfopristin recipients versus 1.3% of recipients of comparator agents. Quinupristin/dalfopristin inhibits cytochrome P450 3A4 and therefore has the potential to increase the plasma concentrations of substrates of this enzyme.
Quinupristin/dalfopristin, the first parenteral streptogramin, offers a unique spectrum of activity against multidrug-resistant gram-positive bacteria. In serious gram-positive infections for which there are other treatment options available, the spectrum of activity and efficacy of quinupristin/ dalfopristin should be weighed against its tolerability and drug interaction profile. However, in VREF or unresponsive MRSA infections, where few proven treatment options exist, quinupristin/dalfopristin should be considered as a treatment of choice for these seriously ill patients.
奎奴普丁/达福普汀是第一种胃肠外应用的链阳菌素类抗菌药物，是两种半合成普那霉素衍生物按30:70（重量/重量）比例组成的合剂。该合剂对多种革兰氏阳性菌具有抑制活性，包括耐甲氧西林葡萄球菌、耐万古霉素粪肠球菌（VREF）、耐药肺炎链球菌、其他链球菌、产气荚膜梭菌和消化链球菌属。该合剂对部分革兰氏阴性呼吸道病原体也具有良好活性，包括卡他莫拉菌、嗜肺军团菌和肺炎支原体。奎奴普丁/达福普汀对粪肠球菌活性较差。该合剂对葡萄球菌和链球菌具有杀菌作用，尽管组成型红霉素耐药可影响其活性。与许多其他药物一样，奎奴普丁/达福普汀对粪肠球菌通常具有抑菌作用。在参与前瞻性紧急使用试验的耐甲氧西林金黄色葡萄球菌（MRSA）或VREF感染患者中，每8或12小时给予7.5mg/kg奎奴普丁/达福普汀，≥64%的患者获得临床或细菌学成功。在VREF感染患者中，对奎奴普丁/达福普汀耐药的情况并不常见（4%的患者）。在3项大型多中心随机试验中，每8或12小时给予7.5mg/kg奎奴普丁/达福普汀的患者，在疑似革兰氏阳性菌引起的复杂性皮肤和皮肤结构感染或医院获得性肺炎（与氨曲南联合使用）患者中，临床成功率与对照药物相似。与奎奴普丁/达福普汀相关的全身性不良事件包括胃肠道事件（恶心、呕吐和腹泻）、皮疹和瘙痒。肌痛和关节痛的总体发生率也为1.3%，尽管在患有多种合并症的患者中报告的发生率较高（2.5%至31%）。如果通过外周静脉给药，静脉相关事件很常见；然而，几种处理方法（如使用中心静脉通路、增加输液量）可能有助于将其发生率降至最低。3.1%的奎奴普丁/达福普汀接受者出现高胆红素血症，而对照药物接受者为1.3%。奎奴普丁/达福普汀抑制细胞色素P450 3A4，因此有可能增加该酶底物的血浆浓度。
奎奴普丁/达福普汀是第一种胃肠外应用的链阳菌素，对多重耐药革兰氏阳性菌具有独特的活性谱。在有其他治疗选择的严重革兰氏阳性菌感染中，应权衡奎奴普丁/达福普汀的活性谱和疗效及其耐受性和药物相互作用情况。然而，在VREF或无反应的MRSA感染中，几乎没有经过验证的治疗选择，应将奎奴普丁/达福普汀视为这些重症患者的首选治疗药物。
