利福平联合疗法对大鼠模型中 MRSA 假体血管移植感染的疗效

IF 5.9 Q1 MICROBIOLOGY
Mikkel Illemann Johansen , Maiken Engelbrecht Petersen , Emma Faddy , Anders Marthinsen Seefeldt , Alexander Alexandrovich Mitkin , Lars Østergaard , Rikke Louise Meyer , Nis Pedersen Jørgensen
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引用次数: 0

摘要

金黄色葡萄球菌是人工血管移植或内植物感染(VGEI)的主要病因,而抗生素的最佳选择尚不明确。我们针对 MRSA USA300 FPR3757 单独使用或与利福平联合使用了磷霉素、达托霉素和万古霉素。对每种抗生素与利福平的协同作用或拮抗作用进行了体外测试,对培养基中活跃生长的细菌和缓冲液中不生长的细菌(包括浮游细胞和生物膜)进行了测试。通过测量移植物上以及脾脏、肝脏和肾脏中的细菌负荷,利用大鼠 VGEI 模型来量化抗生素在体内的疗效。然而,杀菌活性的定量分析显示,对生物膜和浮游细胞都有很强的拮抗作用。只有在处理活性细菌时才能观察到这种效果,因为所有抗生素对非活性细胞的作用都很小或没有作用。只有达托霉素对非活性细胞有一定的杀菌作用。对 VGEI 治疗的体内评估与体外结果形成了鲜明对比。利福平大大提高了达托霉素和万古霉素的疗效。我们的研究表明,达托霉素与利福平联用对 MRSA 引起的 VGEI 有很好的疗效。此外,我们还展示了在实验室培养基中对抗生素组合的体外评估并不能预测它们在体内对 VGEI 的治疗效果,这可能是由于细菌的新陈代谢状态不同造成的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy of rifampicin combination therapy against MRSA prosthetic vascular graft infections in a rat model

Staphylococcus aureus is a major cause of prosthetic vascular graft or endograft infections (VGEIs) and the optimal choice of antibiotics is unclear. We investigated various antibiotic choices as either monotherapy or combination therapy with rifampicin against MRSA in vitro and in vivo.

Fosfomycin, daptomycin and vancomycin alone or in combination with rifampicin was used against MRSA USA300 FPR3757. Each antibiotic was tested for synergism or antagonism with rifampicin in vitro, and all antibiotic regimens were tested against actively growing bacteria in media and non-growing bacteria in buffer, both as planktonic cells and in biofilms. A rat model of VGEI was used to quantify the therapeutic efficacy of antibiotics in vivo by measuring bacterial load on grafts and in spleen, liver and kidneys.

In vitro, rifampicin combinations did not reveal any synergism or antagonism in relation to growth inhibition. However, quantification of bactericidal activity revealed a strong antagonistic effect, both on biofilms and planktonic cells. This effect was only observed when treating active bacteria, as all antibiotics had little or no effect on inactive cells. Only daptomycin showed some biocidal activity against inactive cells. In vivo evaluation of therapy against VGEI contrasted the in vitro results. Rifampicin significantly increased the efficacy of both daptomycin and vancomycin. The combination of daptomycin and rifampicin was by far the most effective, curing 8 of 13 infected animals.

Our study demonstrates that daptomycin in combination with rifampicin shows promising potential against VGEI caused by MRSA. Furthermore, we show how in vitro evaluation of antibiotic combinations in laboratory media does not predict their therapeutic effect against VGEI in vivo, presumably due to a difference in the metabolic state of the bacteria.

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来源期刊
Biofilm
Biofilm MICROBIOLOGY-
CiteScore
7.50
自引率
1.50%
发文量
30
审稿时长
57 days
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