Anstead Gregory M, Cadena Jose, Javeri Heta
Medicine Service, South Texas Veterans Health Care System, San Antonio, TX, USA.
Methods Mol Biol. 2014;1085:259-309. doi: 10.1007/978-1-62703-664-1_16.
This chapter reviews data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review covers findings reported in the English language medical literature up to January of 2013. Despite the emergence of resistant and multidrug-resistant S. aureus, we have seven effective drugs in clinical use for which little resistance has been observed: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline, telavancin, ceftaroline, and daptomycin. However, vancomycin is less effective for infections with MRSA isolates that have a higher MIC within the susceptible range. Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections (SSTIs); whether it is drug of choice in pneumonia remains debatable. Daptomycin has shown to be non-inferior to either vancomycin or β-lactams in the treatment of staphylococcal SSTIs, bacteremia, and right-sided endocarditis. Tigecycline was also non-inferior to comparator drugs in the treatment of SSTIs, but there is controversy about whether it is less effective than other therapeutic options in the treatment of more serious infections. Telavancin has been shown to be non-inferior to vancomycin in the treatment of SSTIs and pneumonia, but has greater nephrotoxicity. Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA; it is non-inferior to vancomycin in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole, doxycycline, rifampin, moxifloxacin, and minocycline are oral anti-staphylococcal agents that may have utility in the treatment of SSTIs and osteomyelitis, but the clinical data for their efficacy is limited. There are also several drugs with broad-spectrum activity against Gm-positive organisms that have reached the phase II and III stages of clinical testing that will hopefully be approved for clinical use in the upcoming years: oritavancin, dalbavancin, omadacycline, tedizolid, delafloxacin, and JNJ-Q2. Thus, there are currently many effective drugs to treat resistant S. aureus infections and many promising agents in the pipeline. Nevertheless, S. aureus remains a formidable adversary, and despite our deep bullpen of potential therapies, there are still frequent treatment failures and unfortunate clinical outcomes. The following discussion summarizes the clinical challenges presented by MRSA, the clinical experience with our current anti-MRSA antibiotics, and the gaps in our knowledge on how to use these agents to most effectively combat MRSA infections.
本章回顾了有关耐药金黄色葡萄球菌感染治疗的数据，尤其是耐甲氧西林金黄色葡萄球菌（MRSA）感染的治疗数据。本综述涵盖了截至2013年1月英文医学文献中报道的研究结果。尽管出现了耐药和多重耐药的金黄色葡萄球菌，但我们目前有七种临床有效的药物，几乎未观察到耐药情况：万古霉素、奎奴普丁-达福普汀、利奈唑胺、替加环素、特拉万星、头孢洛林和达托霉素。然而，对于敏感范围内最低抑菌浓度（MIC）较高的MRSA菌株感染，万古霉素的疗效较差。利奈唑胺可能是治疗复杂性MRSA皮肤和软组织感染（SSTIs）的首选药物；在治疗肺炎方面它是否为首选药物仍存在争议。在治疗葡萄球菌SSTIs、菌血症和右侧心内膜炎方面，达托霉素已显示出不劣于万古霉素或β-内酰胺类药物。在治疗SSTIs方面，替加环素也不劣于对照药物，但在治疗更严重感染时它是否比其他治疗选择效果更差存在争议。在治疗SSTIs和肺炎方面，特拉万星已显示出不劣于万古霉素，但肾毒性更大。头孢洛林是一种对MRSA有活性的广谱头孢菌素；在治疗SSTIs方面它不劣于万古霉素。克林霉素、甲氧苄啶-磺胺甲恶唑、多西环素、利福平、莫西沙星和米诺环素是口服抗葡萄球菌药物，可能对治疗SSTIs和骨髓炎有用，但它们疗效的临床数据有限。还有几种对革兰氏阳性菌有广谱活性的药物已进入临床试验的II期和III期，有望在未来几年获批临床使用：奥利万星、达巴万星、奥玛环素、特地唑胺、德拉氟沙星和JNJ-Q2。因此，目前有许多有效药物可用于治疗耐药金黄色葡萄球菌感染，还有许多有前景的药物正在研发中。尽管如此，金黄色葡萄球菌仍然是一个强大的对手，尽管我们有大量潜在的治疗方法，但治疗失败和不良临床结果仍很常见。以下讨论总结了MRSA带来的临床挑战、我们目前抗MRSA抗生素的临床经验以及我们在如何使用这些药物最有效地对抗MRSA感染方面的知识空白。
