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黄芩联合喹诺酮类药物作用沙门氏菌体外试验研究

通讯作者: 毛敏婕, evel-2002@163.com
DOI:10.12201/bmr.202603.00050
声明:预印本系统所发表的论文仅用于最新科研成果的交流与共享,未经同行评议,因此不建议直接应用于指导临床实践。

In Vitro Study on the Combined Effect of Scutellaria baicalensis and Quinolones Against Salmonella.

Corresponding author: MAO MINJIE, evel-2002@163.com
  • 摘要:目的 分析嘉兴大学附属医院临床分离沙门氏菌的血清型分布、多位点序列分型特征,探讨喹诺酮类药物与黄芩有效成分的联合抗菌作用,菌株生物膜形成能力及药物抑制效果。方法 随机选取2023-2024年该院检出的19株沙门氏菌,采用二代基因测序进行序列类型(sequence type,ST)分型,玻片凝集法完成血清分型,微量肉汤稀释法测定单药最小抑菌浓度(minimal inhibitory concentration,MIC)、最小杀菌浓度(minimum bactericidal concentration,MBC),用棋盘格稀释法计算部分抑菌浓度指数评价药物联合效应,结晶紫染色法测定生物膜形成及药物抑制率。结果 鼠伤寒沙门氏菌80%为ST 34基因型,主要分离于粪便样本;肠炎沙门氏菌均为ST 11基因型。单药 MIC 结果显示:环丙沙星、左氧氟沙星MIC主要集中在0.03125-0.5 μg·mL-1,阿奇霉素MIC主要集中在4-8 μg·mL-1,黄芩苷单药MIC均为16 mg·mL-1,黄芩素单药MIC分布在 2-16 mg·mL-1。联合药敏显示:无阿奇霉素干预时,左氧氟沙星与黄芩苷联用抗菌效果,优于环丙沙星与黄芩苷联用;加入阿奇霉素后,黄芩素与左氧氟沙星主要呈相加作用,黄芩苷与环丙沙星则表现为协同作用,协同率从9.09%提升至45.45%。生物膜相关结果显示:肠炎沙门氏菌生物膜形成能力强于鼠伤寒沙门氏菌;1×MIC比 1/2×MIC 左氧氟沙星对生物膜抑制效果显著提高(P=0.001),1×MIC与1/2×MIC的环丙沙星则对沙门氏菌生物膜抑制率无统计学差异(P=0.347)。结论 黄芩有效成分(黄芩苷、黄芩素)与喹诺酮类药物联用对沙门氏菌有一定抑制作用,左氧氟沙星最小抑菌浓度的抑制生物膜效果显著优于亚抑菌浓度,而环丙沙星则无此差异,阿奇霉素可增强环丙沙星与黄芩苷联用的抑菌活性。

    关键词: 沙门氏菌,黄芩,喹诺酮类药物,联合药敏,生物膜,抑制率

     

    Abstract: Objective To analyze the serotype distribution and multilocus sequence typing characteristics of Salmonella strains isolated clinically from Affiliated Hospital of Jiaxing University, investigate the combined antimicrobial effects of quinolones and active components of Scutellaria baicalensis, and evaluate the biofilm-forming capacity of the strains as well as the inhibitory effects of drugs.Methods A total of 19 Salmonella strains detected in the hospital during 2023-2024 were randomly selected. Second-generation gene sequencing was employed for sequence type (ST) typing, slide agglutination for serotyping, and broth microdilution for determining minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of single drugs.The checkerboard dilution method was used to calculate the fractional inhibitory concentration index for evaluating drug combination effects, while crystal violet staining was employed to measure biofilm formation and drug inhibition rates.Results Approximately 80% of Salmonella Typhimurium isolates were identified as sequence type (ST) 34, primarily detected in fecal samples. All Salmonella Enteritidis isolates belonged to genotype ST 11. The MIC range for ciprofloxacin (CIP) and levofloxacin (LEV) was predominantly 0.03125-0.5 μg?mL?1, while azithromycin MIC values mainly fell within 4-8 μg?mL?1. The MIC of baicalin monotherapy was consistently 16 mg?mL?1, and baicalein monotherapy exhibited MIC values ranging from 2-16 mg?mL?1. In terms of combined drug susceptibility, in the absence of azithromycin, the combination of levofloxacin and baicalin showed superior antibacterial effects compared to ciprofloxacin combined with baicalin.In the presence of azithromycin, combinations of baicalein and levofloxacin primarily exhibited additive effects, while those of baicalin and ciprofloxacin demonstrated synergism, with the synergy rate increasing from 9.09% to 45.45%. Salmonella Enteritidis exhibited stronger biofilm formation capability than Salmonella Typhimurium. The inhibitory effect of 1×MIC levofloxacin on biofilms was significantly higher than that of 1/2×MIC(P=0.001), whereas no significant difference in the biofilm inhibition rate was observed between 1×MIC and 1/2×MIC CIP against Salmonella (P=0.347).Conclusion The combined use of active components of Scutellaria baicalensis (baicalin and baicalein) with quinolone antibiotics exhibits certain inhibitory effects against Salmonella. The biofilm inhibition effect of levofloxacin at its minimum inhibitory concentration is significantly superior to that at sub-inhibitory concentrations, while no such difference is observed with ciprofloxacin. Azithromycin can enhance the antibacterial activity of the combination of ciprofloxacin and baicalin.

    Key words: Salmonella, Scutellaria; baicalensis, quinolone, combined; drug sensitivity, biofilm, inhibition; rate.

    提交时间:2026-03-13

    版权声明:作者本人独立拥有该论文的版权,预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。
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  • 序号 提交日期 编号 操作
    1 2026-01-19

    10.12201/bmr.202603.00050V1

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高庆, 王亚华, 钱佳栋, 濮至谊, 沈斌, 吕青山, 毛敏婕. 黄芩联合喹诺酮类药物作用沙门氏菌体外试验研究. 2026. biomedRxiv.202603.00050

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