Davis J S, Van Hal S, Tong S Y C
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, Australia.
Semin Respir Crit Care Med. 2015 Feb;36(1):3-16. doi: 10.1055/s-0034-1396906. Epub 2015 Feb 2.
Outcomes from methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively poor, at least in part due to the limitations of vancomycin (the current standard treatment for MRSA). Combination antibiotic treatment for MRSA infections is an attractive alternative as it could address most of vancomycin's shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies. Multiple combinations have been tested and have been either antagonistic, indifferent, or have had conflicting findings in various studies. This includes combinations of two primarily active agents (such as vancomycin plus daptomycin or linezolid), or the addition of gentamicin or rifampin to either vancomycin or daptomycin. However, hope on this front has come from an unexpected quarter. Although MRSA is by definition inherently resistant to nearly all β-lactam antibiotics, this class of drugs has consistently shown evidence of synergy with either daptomycin or vancomycin in over 25 separate in vitro studies, and a limited number of animal and human observational studies. However, there are currently insufficient data to recommend β-lactam combination therapy in routine clinical use. Results of current and planned randomized controlled trials of this strategy are awaited.
耐甲氧西林金黄色葡萄球菌（MRSA）感染的预后相对较差，至少部分原因是万古霉素（目前治疗MRSA的标准药物）存在局限性。MRSA感染的联合抗生素治疗是一种有吸引力的替代方案，因为它可以解决万古霉素的大部分缺点，包括组织穿透力差、细菌杀灭缓慢以及某些MRSA菌株出现耐药性。然而，MRSA感染联合治疗的理论前景在大多数体外和动物研究中并未得到证实。多种联合方案已经过测试，在各种研究中，它们要么具有拮抗作用、无作用，要么结果相互矛盾。这包括两种主要活性剂的联合（如万古霉素加达托霉素或利奈唑胺），或者在万古霉素或达托霉素中添加庆大霉素或利福平。然而，这方面的希望来自一个意想不到的领域。虽然根据定义，MRSA对几乎所有β-内酰胺抗生素都具有固有耐药性，但在超过25项独立的体外研究以及有限数量的动物和人体观察性研究中，这类药物一直显示出与达托霉素或万古霉素协同作用的证据。然而，目前尚无足够的数据推荐在常规临床使用中采用β-内酰胺联合治疗。目前正在进行和计划中的该策略随机对照试验的结果值得期待。
