Meeker Daniel G, Beenken Karen E, Mills Weston B, Loughran Allister J, Spencer Horace J, Lynn William B, Smeltzer Mark S
Department of Microbiology & Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Antimicrob Agents Chemother. 2016 Sep 23;60(10):5688-94. doi: 10.1128/AAC.01251-16. Print 2016 Oct.
We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when tested in vivo in a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associated S. aureus infections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.
我们使用了导管相关生物膜形成的体外和体内模型，以比较在已形成生物膜的特定情况下，对耐甲氧西林金黄色葡萄球菌（MRSA）有效的抗生素的相对活性。结果表明，在体外条件下，达托霉素和头孢洛林相对于彼此表现出相当的活性，并且比万古霉素、替考拉宁、奥利万星、达巴万星或替加环素具有更高的活性。当使用由USA300耐甲氧西林菌株LAC和USA200甲氧西林敏感菌株UAMS-1形成的已建立生物膜进行评估时，情况确实如此。正如预期的那样，由于LAC是一种MRSA菌株，苯唑西林对UAMS-1的活性比对LAC的活性更高。然而，即使对UAMS-1，苯唑西林的活性也低于达托霉素和头孢洛林。在脂糖肽类中，替考拉宁表现出最大的总体活性。具体而言，当针对由LAC形成的生物膜进行测试时，替考拉宁表现出比奥利万星或达巴万星更高的活性，并且是唯一能够将活菌数量减少到检测限以下的脂糖肽。对于由UAMS-1形成的生物膜，替考拉宁和达巴万星相对于彼此表现出相当的活性，并且比奥利万星具有更高的活性。重要的是，在导管相关生物膜形成的小鼠体内模型中进行测试时，头孢洛林是唯一一种比万古霉素表现出更高活性的抗生素。这些结果强调，在治疗与生物膜相关的金黄色葡萄球菌感染时，需要考虑使用除万古霉素之外的抗生素，最值得注意的是头孢洛林，包括通过在治疗这些感染时常用于局部抗生素递送的基于基质的抗生素递送方法。
