Combined efficacy of clarithromycin plus vancomycin in mice with device-related infection by biofilms-forming Staphylococcus aureus

  • Shigeru Fujimura, Research Division for Development of Anti-infected agents, Institute of Development, Aging and Cancer, Tohoku University, Japan
  • Dr Tetsuro Sato, Sendai Orthopaedic Hospital, Japan
  • Dr Toshiaki Kikuchi, Development of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Japan
  • Jamal Zaini, Development of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Japan
  • Dr Akira Watanabe, Research Division for Development of Anti-infected agents, Institute of Development, Aging and Cancer, Tohoku University, Japan

    • Object: Staphylococcal biofilms also pose an important problem, especially in infection after orthopedic surgery using medical devices. Clarithromycin (CAM) has an effect of the biofilm elimination against a wide variety of aerobic and anaerobic bacteria. In the previous study, we have shown that the combined treatment with CAM and vancomycin (VCM) is effective for eradicating staphylococcal biofilms on medical devices in vitro. To confirm in vivo efficacy of the combined eradication therapy to device- related infection, we investigated the combined treatment with CAM and VCM against S. aureus on the titanium device in mice.
    Methods: The bacterial strain used was S. aureus JCM2413. S.aureus was incubated with the titanium washer (device) in TSB supplemented with 1% glucose at 37oC under anaerobic conditions for 72h. The titanium washer covered with biofilms-forming S. aureus was implanted in murine muscle tissue around the bone. C57BL/6 mice were injected intravenously with CAM and intraperitonealy with VCM twice daily for three days. To confirm eradication of biofilms and S.aureus strains, the resected washer was monitored using SEM.
    Results and Conclusions : Dense colonization and biofilms were seen on the washer of the controls that received saline, saline plus CAM, or saline plus VCM. The combined treatment with CAM plus VCM removed biofilms and showed S. aureus eradication effect. Staphylococcal biofilms demonstrated resistance to most antibiotics, including VCM. These in vivo data support the hypothesis that the combined treatment with CAM plus VCM may be an effective for eradicating staphylococcal biofilms in device-related infection.