抗寄生虫药氟雷拉纳对金黄色葡萄球菌的抗菌活性研究  

Antimicrobial effects of the anti-parasite drug flurlalner against Staphylococcus aureus

作　　者：唐海涛 王社盈 Tang Haitao;Wang Sheying(Department of Thoracic Surgery,The Affiliated Changsha Hospital of Xiangya School of Medicine,Central South University,Changsha 410005;Department of Clinical Laboratory,The Affiliated Changsha Hospital of Xiangya School of Medicine,Central South University,Changsha 410005)

机构地区：[1]中南大学湘雅医学院附属长沙医院(长沙市第一医院)胸外科,长沙410005 [2]中南大学湘雅医学院附属长沙医院(长沙市第一医院)检验科,长沙410005

出　　处：《中国抗生素杂志》2024年第5期552-559,共8页Chinese Journal of Antibiotics

基　　金：长沙市科技计划(No.kzd2001088)。

摘　　要：目的研究抗寄生虫药物氟雷拉纳对金黄色葡萄球菌的抗菌活性。方法金黄色葡萄球菌临床菌株SA1901和SA1902于2023年5月份收集自脓胸患者的胸水培养标本;通过微量肉汤稀释实验和时间-杀菌曲线检测金黄色葡萄球菌对氟雷拉纳的敏感性;通过连续诱导耐药实验检测氟雷拉纳的耐药诱导能力;通过构建持留菌、生物被膜抗菌实验以及激光共聚焦显微镜检测氟雷拉纳对金黄色葡萄球菌持留菌和生物被膜的抗菌活性;最后,棋盘稀释实验用于检测氟雷拉纳与氨基糖苷类抗菌药物的联用效果。结果氟雷拉纳对金黄色葡萄球菌的最低抑菌浓度(minimal inhibitory concentration,MIC)和最低杀菌浓度分别为4~8μg/m L和8~16μg/m L;通过时间-杀菌曲线发现亚抑菌浓度的氟雷拉纳即可有效抑制细菌的增殖;氟雷拉纳连续处理金黄色葡萄球菌15 d也未见耐药突变的形成;8×MIC的氟雷拉纳作用ATCC 25923持留菌4 h可使其活菌计数从(8.97±0.35)Log_(10)CFU/m L降低到(7.47±0.09)Log_(10)CFU/m L(t=7.17,P=0.002),使USA300持留菌从(9.35±0.31)Log_(10)CFU/m L降低到(6.79±0.20)Log_(10)CFU/m L(t=12.04,P<0.001);1×MIC的氟雷拉纳可显著抑制USA300生物被膜的形成,使其生物被膜的形成量从(2.41±0.12)降低到(0.20±0.06)(t=44.03,P<0.0001);1×MIC的氟雷拉纳还能显著清除已形成的生物被膜,使其生物被膜的总量从(3.02±0.02)减少到(2.04±0.39)(t=5.58,P=0.0008);通过棋盘稀释试验和活菌计数发现氟雷拉纳与阿米卡星联用具有协同抗菌活性,其协同抑菌指数为0.375。结论氟雷拉纳对金黄色葡萄球菌具有显著的抗菌作用,且与阿米卡星联用具有协同抗菌活性。Objective This study aimed to investigate the antimicrobial effects of the anti-parasite drug fluralaner against Staphylococcus aureus.Methods S.aureus clinical isolates of SA1901 and SA1902 were collected from the thoracic fluid of pyothorax patients in May 2023.The antimicrobial susceptibility of fluralaner against S.aureus was determined by the micro-broth dilution assay and time-killing curves.The consecutive resistanceinducing assay was used to detect the resistance-inducing ability of fluralaner.The persister cell killing assay,the anti-biofilm assay and the laser confocal microscope were used to explore the anti-persister and anti-biofilm activities of fluralaner.Last,the combinational antimicrobial effects between fluralaner and aminoglycosides were determined by the checkerboard dilution assay.Results The minimal inhibitory concentration(MIC)and minimal bactericidal concentration of fluralaner against S.aureus were 4~8μg/m L and 8~16μg/m L,respectively.The subMIC of fluralaner was found to effectively inhibit bacterial growth by the time-killing assay.No resistant mutation was observed even after fluralaner treatment for 15 consecutive days.After 4 h treatment,8×MIC of fluralaner could significantly reduce the viable persister cells of ATCC 25923 and USA300 from(8.97±0.35)Log10 CFU/m L to(7.47±0.09)Log_(10)CFU/m L(t=7.17,P=0.002),and from(9.35±0.31)Log_(10)CFU/m L to(6.79±0.20)Log_(10)CFU/m L(t=12.04,P<0.001),respectively.Fluralaner could significantly inhibit the biofilm formation of USA300 from(2.41±0.12)to(0.20±0.06)(t=44.03,P<0.0001)at the concentration of 1×MIC;and 1×MIC of fluralaner could also significantly eradicate the pre-formed biofilm form(3.02±0.02)to(2.04±0.39)(t=5.58,P=0.0008);By checkerboard dilution assay and viable bacteria counting,amikacin was found to be synergistic with fluralaner against S.aureus with a synergistic antiacterial index of 0.375.Conclusion Fluralaner showed significant antimicrobial effects against S.aureus and could be synergistic with amikacin against S

关 键 词：金黄色葡萄球菌 氟雷拉纳 持留菌 生物被膜 抗菌药物 

分 类 号：R632[医药卫生—外科学]