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莫匹罗星与单萜类化合物(百里香酚、薄荷醇和1,8-桉叶素)单用及联用对金黄色葡萄球菌浮游菌和生物膜生长的抗菌效力

Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth.

作者信息

Kifer Domagoj, Mužinić Vedran, Klarić Maja Šegvić

机构信息

Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.

出版信息

J Antibiot (Tokyo). 2016 Sep;69(9):689-96. doi: 10.1038/ja.2016.10. Epub 2016 Feb 17.

Abstract

Staphylococcus aureus is one of the most commonly isolated microbes in chronic rhinosinusitis (CRS) that can be complicated due to the formation of a staphylococcal biofilm. In this study, we investigated antimicrobial efficacy of single mupirocin and three types of monoterpenes (thymol, menthol and 1,8-cineole) as well as mupirocin-monoterpene combinations against S. aureus ATCC 29213 and 5 methicilin-resistant S. aureus strains (MRSA) grown in planktonic and biofilm form. MIC against planktonic bacteria as well as minimum biofilm-eliminating concentrations (MBECs) and minimum biofilm inhibitory concentrations (MBICs) were determined by TTC and MTT reduction assay, respectively. The MICs of mupirocin (0.125-0.156 μg ml(-1)) were three orders of magnitude lower than the MICs of monoterpenes, which were as follows: thymol (0.250-0.375 mg ml(-1)) > menthol (1 mg ml(-1)) > 1,8-cineole (4-8 mg ml(-1)). Mupirocin-monoterpene combinations showed indifferent effect as compared with MICs of single substances. Mupirocin (0.016-2 mg ml(-1)) failed to destroy the biofilm. The MBECs of thymol and menthol were two- to sixfold higher than their MICs, while 1,8-cineole exerted a weak antibiofilm effect with MBECs 16- to 64-fold higher than MICs. Mixture of mupirocin and 1,8 cineole exerted a potentiated biofilm-eliminating effect, mupirocin-menthol showed antagonism, while effect of thymol-mupirocin mixture was inconclusive. MBICs of antimicrobials were close to their MICs, except 1,8-cineole, MBIC was about three- to fivefold higher. Dominant synergy was observed for mixtures of mupirocin and menthol or thymol, whereas mupirocin-1,8-cineol exerted an indifferent or additive biofilm inhibitory effect. Particular combinations of mupirocin and the monoterpenes could be applied in CRS therapy in order to eliminate or prevent bacterial biofilm growth.

摘要

金黄色葡萄球菌是慢性鼻窦炎(CRS)中最常分离出的微生物之一,由于葡萄球菌生物膜的形成,其可能会引发并发症。在本研究中,我们调查了莫匹罗星单药、三种单萜类化合物(百里香酚、薄荷醇和1,8-桉叶素)以及莫匹罗星与单萜类化合物的组合对浮游状态和生物膜状态下生长的金黄色葡萄球菌ATCC 29213以及5株耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌效果。分别通过TTC和MTT还原试验测定了对浮游细菌的最低抑菌浓度(MIC)以及最低生物膜清除浓度(MBEC)和最低生物膜抑制浓度(MBIC)。莫匹罗星的MIC(0.125 - 0.156μg/ml)比单萜类化合物的MIC低三个数量级,单萜类化合物的MIC如下:百里香酚(0.250 - 0.375mg/ml)>薄荷醇(1mg/ml)>1,8-桉叶素(4 - 8mg/ml)。与单药的MIC相比,莫匹罗星与单萜类化合物的组合效果不明显。莫匹罗星(0.016 - 2mg/ml)无法破坏生物膜。百里香酚和薄荷醇的MBEC比其MIC高2至6倍,而1,8-桉叶素的抗生物膜作用较弱,其MBEC比MIC高16至64倍。莫匹罗星与1,8-桉叶素的混合物具有增强的生物膜清除作用,莫匹罗星与薄荷醇表现出拮抗作用,而百里香酚与莫匹罗星混合物的作用尚无定论。除1,8-桉叶素外,抗菌剂的MBIC接近其MIC,1,8-桉叶素的MBIC约高3至5倍。观察到莫匹罗星与薄荷醇或百里香酚的混合物具有显著协同作用,而莫匹罗星与1,8-桉叶素表现出不明显或相加的生物膜抑制作用。莫匹罗星与单萜类化合物的特定组合可应用于CRS治疗,以消除或预防细菌生物膜的生长。

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