Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran.
Eur J Clin Microbiol Infect Dis. 2018 Mar;37(3):443-454. doi: 10.1007/s10096-018-3189-7. Epub 2018 Jan 20.
The rapid increase of drug resistance and failure of available antibiotics to treat biofilm-associated infections is of great health concern. Accordingly, our study aimed to evaluate the synergistic antibacterial, biofilm inhibitory, and biofilm removal activities of melittin in combination with colistin, imipenem, and ciprofloxacin against multidrug-resistant (MDR) strong biofilm producer Acinetobacter baumannii isolates. The kinetics of biofilm formation were evaluated for the isolates for 144 h. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and biofilm removal activities for melittin and combinations with antibiotics were determined. Inhibition of biofilm-associated protein (bap) expression by melittin was evaluated with real-time polymerase chain reaction (PCR). Field emission scanning electron microscopy (FE-SEM) was used to visualize the effect of synergism on the inhibition of biofilm production. The geometric means of the fractional inhibitory concentration index (FICi) for melittin-colistin, melittin-imipenem, and melittin-ciprofloxacin combinations were calculated as 0.31, 0.24, and 0.94, respectively. Comparing the geometric means of the removal activity for melittin, colistin, imipenem, and combinations of them in both 6 and 24 h showed a significant difference between the groups (p-value < 0.05). Exposure to melittin induced a statistically significant downregulation of bap mRNA levels in all isolates at sub-MIC doses. Analysis of the FE-SEM results demonstrated that the synergism of melittin-colistin at 0.125-0.25 μg inhibited biofilm formation completely. In conclusion, our findings indicate that melittin possesses considerable potential for use in combination with colistin and imipenem to treat infections caused by MDR strong biofilm producer A. baumannii isolates.
耐药性的迅速增加以及现有抗生素治疗生物膜相关感染的失败引起了极大的健康关注。因此，我们的研究旨在评估蜂毒素与多粘菌素、亚胺培南和环丙沙星联合使用对多重耐药（MDR）强生物膜产生菌鲍曼不动杆菌分离株的协同抗菌、生物膜抑制和生物膜去除活性。我们评估了这些分离株的生物膜形成动力学，共 144 小时。测定了蜂毒素和抗生素组合的最小抑菌浓度（MIC）、最小杀菌浓度（MBC）、最小生物膜抑制浓度（MBIC）和生物膜去除活性。采用实时聚合酶链反应（PCR）评估蜂毒素对生物膜相关蛋白（bap）表达的抑制作用。用场发射扫描电子显微镜（FE-SEM）观察协同作用对抑制生物膜产生的影响。计算了蜂毒素-多粘菌素、蜂毒素-亚胺培南和蜂毒素-环丙沙星组合的部分抑菌浓度指数（FICI）几何平均值分别为 0.31、0.24 和 0.94。比较蜂毒素、多粘菌素、亚胺培南以及它们组合在 6 小时和 24 小时的去除活性的几何平均值，各组之间存在显著差异（p 值 < 0.05）。在亚 MIC 剂量下，蜂毒素诱导所有分离株的 bap mRNA 水平统计学显著下调。FE-SEM 结果分析表明，0.125-0.25 μg 浓度的蜂毒素-多粘菌素协同作用可完全抑制生物膜形成。总之，我们的研究结果表明，蜂毒素具有与多粘菌素和亚胺培南联合使用治疗由 MDR 强生物膜产生菌鲍曼不动杆菌引起的感染的巨大潜力。
