Background The global problem of antibiotic resistance requires the search for and development of new methods of treatment. One of the promising strategies is the use of low doses of antimicrobial peptides, in particular, human defensins HNP-1, hBD-1, and hBD-3, in combination with antibacterial drugs already used in clinical practice. This approach may be used to increase the effectiveness of conventional antibiotics. However, this requires thorough study of the effectiveness of defensins in combination with antibiotics against a large number of bacterial strains with known phenotypes of antibiotic resistance. The aim of this work was to study the antibacterial effect of HNP-1, hBD-1 and hBD-3 in combination with rifampicin or amikacin against clinical isolates of Staphylococcus aureus (n = 27) and Escherichia coli (n = 24) collected from hospitalized patients. Methods The standard checkerboard assay was used to determine minimum inhibitory concentrations (MICs) of antimicrobials. The combined microbicidal effects of two substances (defensin + conventional antibiotic) were assessed by the fractional inhibitory concentration index (FICI). Results The highest anti-staphylococcal activity (including methicillin-resistant strains) among defensins was demonstrated by hBD-3 that had MIC of 1 (0.5–4) mg/L (hereinafter, MIC values are presented as median and interquartile range). The MIC of HNP-1 against S. aureus was 4 (2–8) mg/L; the MIC of hBD-1 was 8 (4–8) mg/L. Against E. coli, the most effective was also found to be hBD-3 that had MIC of 4 (4–8) mg/L; the MIC of HNP-1 was 12 (4–32) mg/L. The combinations of HNP-1 + rifampicin and hBD-3 + rifampicin demonstrated synergistic effects against S. aureus. Against E. coli, combinations of HNP-1 + amikacin and hBD-3 + amikacin also showed synergy of action.

中文翻译：

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人类防御素对金黄色葡萄球菌和大肠杆菌的抗菌活性


背景抗生素耐药性的全球性问题需要寻找和开发新的治疗方法。其中一种有前景的策略是使用低剂量的抗菌肽，特别是人类防御素 HNP-1、hBD-1 和 hBD-3，与已在临床实践中使用的抗菌药物相结合。这种方法可用于提高常规抗生素的有效性。然而，这需要深入研究防御素与抗生素联合使用对大量具有已知抗生素耐药表型的细菌菌株的有效性。这项工作的目的是研究 HNP-1、hBD-1 和 hBD-3 与利福平或阿米卡星联合使用对从临床分离的金黄色葡萄球菌 (n = 27) 和大肠杆菌 (n = 24) 分离的抗菌效果。住院病人。方法 使用标准棋盘测定法确定抗菌药物的最低抑菌浓度 (MIC)。通过分数抑制浓度指数 (FICI) 评估两种物质（防御素 + 常规抗生素）的综合杀菌效果。结果防御素中抗葡萄球菌活性（包括耐甲氧西林菌株）最高的是hBD-3，其MIC为1（0.5-4）mg/L（下文中MIC值以中位数和四分位数范围表示）。 HNP-1 对金黄色葡萄球菌的 MIC 为 4 (2–8) mg/L； hBD-1 的 MIC 为 8 (4–8) mg/L。针对大肠杆菌，还发现最有效的是 hBD-3，其 MIC 为 4 (4–8) mg/L； HNP-1 的 MIC 为 12 (4–32) mg/L。 HNP-1 + 利福平和 hBD-3 + 利福平的组合对金黄色葡萄球菌具有协同作用。反对E。 在大肠杆菌中，HNP-1 + 阿米卡星和 hBD-3 + 阿米卡星的组合也显示出协同作用。