Dhand Abhay, Sakoulas George
Westchester Medical Center, New York Medical College, Valhalla, New York.
University of California, San Diego School of Medicine, La Jolla, California.
Clin Ther. 2014 Oct 1;36(10):1303-16. doi: 10.1016/j.clinthera.2014.09.005. Epub 2014 Oct 23.
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important nosocomial pathogens. Resistance to antibiotic therapy has been known to emerge especially in clinically complex scenarios, resulting in challenges in determining optimal treatment of serious MRSA. Daptomycin, in combination with other antibiotics, has been successfully used in the treatment of these infections, with the aims of resulting in reducing the prevention of antimicrobial resistance and increased killing compared with daptomycin monotherapy.
This article reviews all the published studies that used daptomycin combination therapy for the treatment of bacteremia and associated complicated infections caused by gram-positive organisms, including MRSA. We discuss the rationale of combination antibiotics and the mechanisms that enhance the activity of daptomycin, with special focus on the role of β-lactam antibiotics.
There are limited clinical data on the use of daptomycin in combination with other antibiotics. Most of this use was as successful salvage therapy in the setting of failing primary, secondary, or tertiary therapy and/or relapsing infection. Synergy between β-lactams and daptomycin is associated with several characteristics, including increased daptomycin binding and β-lactam-mediated potentiation of innate immunity, but the precise molecular mechanism is unknown.
Use of daptomycin in combination with other antibiotics, especially β-lactams, offers a promising treatment option for complicated MRSA bacteremia in which emergence of resistance during treatment may be anticipated. Because it is currently not possible to differentiate complicated from uncomplicated bacteremia at the time of presentation, combination therapy may be considered as first-line therapy, with de-escalation to monotherapy in uncomplicated cases and cases with stable pharmacologic and surgical source control.
耐甲氧西林金黄色葡萄球菌（MRSA）已成为最重要的医院感染病原体之一。已知在临床复杂情况下尤其容易出现对抗生素治疗的耐药性，这给确定严重MRSA的最佳治疗带来了挑战。达托霉素与其他抗生素联合使用已成功用于治疗这些感染，目的是与达托霉素单药治疗相比，减少抗菌药物耐药性的发生并增强杀菌效果。
本文回顾了所有已发表的使用达托霉素联合疗法治疗由革兰氏阳性菌（包括MRSA）引起的菌血症及相关复杂感染的研究。我们讨论了联合使用抗生素的基本原理以及增强达托霉素活性的机制，特别关注β-内酰胺类抗生素的作用。
关于达托霉素与其他抗生素联合使用的临床数据有限。这种联合使用大多是在一线、二线或三线治疗失败和/或复发感染的情况下作为成功的挽救疗法。β-内酰胺类药物与达托霉素之间的协同作用与几个特征有关，包括达托霉素结合增加和β-内酰胺介导的先天免疫增强，但确切的分子机制尚不清楚。
将达托霉素与其他抗生素（尤其是β-内酰胺类抗生素）联合使用，为治疗可能预期在治疗期间出现耐药性的复杂MRSA菌血症提供了一种有前景的治疗选择。由于在就诊时目前无法区分复杂菌血症和非复杂菌血症，联合治疗可被视为一线治疗，在非复杂病例以及药物和手术源控制稳定的病例中可降级为单药治疗。
