Background

The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has rapidly increased. This study aimed to assess the effect of Coptis chinensis and its compounds on the minimal inhibitory concentrations (MICs) of eight antibiotics against CRKP.

Methods

Cell cultures were used to investigate the effects of C. chinensis and its compounds on the MICs of eight antibiotics against CRKP. The MICs for antibiotics alone and antibiotics with C. chinensis or compounds were measured and compared. Furthermore, the effects of C. chinensis on cell membrane injury and intracellular adenosine triphosphate (ATP) CRKP concentration were also measured. The Mann–Whitney rank-sum test was used to analyze the differences between means.

Results

C. chinensis exhibits a notable MIC bacteriostatic effect at 5 mg/mL on CRKP. A significant MIC reduction against CRKP exists when C. chinensis was added to colistin and colistin-containing two-antibiotic combinations. Moreover, C. chinensis could damage cell membrane integrity and decrease intracellular ATP concentration in CRKP. Thus, C. chinensis exhibits antimicrobial activity superiority with colistin against CRKP. Furthermore, the effects of identified compounds in C. chinensis on the MICs of colistin, four-to eight-, two-to four-, and one-to two-fold reductions were found in ferulic acid, magnoflorine, and jatrorrhizine hydrochloride, respectively. Among these compounds, ferulic acid destroys membrane integrity and decreases intracellular ATP concentration.

Conclusion

C. chinensis and ferulic acid can potentiate the antimicrobial activity of colistin and may represent a promising component of combination therapy against CRKP infections in a clinical setting.

中文翻译：

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黄连在耐碳青霉烯类肺炎克雷伯菌抗生素敏感性中的作用

背景

耐碳青霉烯类肺炎克雷伯菌（CRKP）的发病率迅速增加。本研究旨在评估黄连及其化合物对 8 种抗生素对 CRKP 的最低抑菌浓度 (MICs) 的影响。

方法

细胞培养物用于研究C. chinensis及其化合物对八种抗生素对 CRKP 的 MIC 的影响。测量并比较了单独使用抗生素和含有C. chinensis或化合物的抗生素的 MIC。此外，还测量了C. chinensis对细胞膜损伤和细胞内三磷酸腺苷 (ATP) CRKP 浓度的影响。Mann-Whitney 秩和检验用于分析平均值之间的差异。

结果

C. chinensis在 5 mg/mL 时对 CRKP 表现出显着的 MIC 抑菌作用。当C. chinensis添加到粘菌素和含有粘菌素的两种抗生素组合中时，对 CRKP 的 MIC 显着降低。此外，C. chinensis可破坏细胞膜完整性并降低 CRKP 中的细胞内 ATP 浓度。因此，C. chinensis与粘菌素对 CRKP 表现出抗微生物活性优势。此外，已鉴定化合物对C. chinensis的影响在多粘菌素的 MIC 上，阿魏酸、木兰花碱和盐酸药根碱分别降低了 4 到 8 倍、2 到 4 倍和 1 到 2 倍。在这些化合物中，阿魏酸会破坏细胞膜完整性并降低细胞内 ATP 浓度。

结论

C. chinensis和阿魏酸可以增强粘菌素的抗菌活性，并可能代表临床环境中针对 CRKP 感染的联合治疗的有希望的组成部分。