Kang Yu Ri, Park Joo-Young, Chung Doo Ryeon, Kang Minhee, Ko Jae-Hoon, Huh Kyungmin, Cho Sun Young, Kang Cheol-In, Peck Kyong Ran
Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Asia Pacific Foundation for Infectious Diseases (APFID), Seoul 06367, Republic of Korea.
Pathogens. 2025 Apr 23;14(5):404. doi: 10.3390/pathogens14050404.
biofilms complicate the treatment of device-related infections. We hypothesized that combining rifampin with fluoroquinolones could eradicate biofilms even in antimicrobial-resistant strains. We determined the synergistic interactions of these combinations in a biofilm model. Thirty methicillin-resistant (MRSA) isolates with varying susceptibility profiles were evaluated. Minimum biofilm eradication concentrations (MBECs) were determined using the Calgary Biofilm Device, and the synergy was assessed using the fractional biofilm eradication concentration (FBEC) index. Scanning electron microscopy (SEM) was performed on one strain, and confocal laser scanning microscopy (CLSM) was conducted on four strains for visualizing and evaluating the biofilm viability. The MBEC for rifampin and levofloxacin were 512 mg/L and 256 mg/L, respectively, and exceeded 1024 mg/L for ciprofloxacin. Synergy was observed in 56.7% of strains for both the rifampin + ciprofloxacin and rifampin + levofloxacin combinations, with no difference between the combinations. A higher ciprofloxacin MBEC (≥16 mg/L) increased the likelihood of synergy with rifampin by 18-fold. SEM and CLSM analyses in a subset of strains confirmed the enhanced biofilm disruption with rifampin + ciprofloxacin compared to ciprofloxacin alone. Our findings suggest that rifampin combined with ciprofloxacin or levofloxacin may synergistically eradicate MRSA biofilms, offering a potential treatment option for device-related infections when alternatives are limited.
生物膜会使与器械相关的感染治疗变得复杂。我们假设利福平与氟喹诺酮类药物联合使用能够根除生物膜,即使在耐药菌株中也是如此。我们在生物膜模型中确定了这些联合用药的协同相互作用。对30株具有不同药敏谱的耐甲氧西林金黄色葡萄球菌(MRSA)分离株进行了评估。使用卡尔加里生物膜装置测定最低生物膜根除浓度(MBECs),并使用生物膜根除浓度分数(FBEC)指数评估协同作用。对其中1株菌株进行了扫描电子显微镜(SEM)检查,对4株菌株进行了共聚焦激光扫描显微镜(CLSM)检查,以观察和评估生物膜活力。利福平和左氧氟沙星的MBEC分别为512mg/L和256mg/L,环丙沙星的MBEC超过1024mg/L。利福平+环丙沙星和利福平+左氧氟沙星联合用药在56.7%的菌株中观察到协同作用,两种联合用药之间无差异。较高的环丙沙星MBEC(≥16mg/L)使与利福平产生协同作用的可能性增加了18倍。对部分菌株进行的SEM和CLSM分析证实,与单独使用环丙沙星相比,利福平+环丙沙星对生物膜的破坏作用增强。我们的研究结果表明,利福平与环丙沙星或左氧氟沙星联合使用可能协同根除MRSA生物膜,在替代治疗选择有限时,为与器械相关的感染提供了一种潜在的治疗选择。