vancomycin + tigecycline + polymyxin B

This combination therapy consists of three potent antibiotics—vancomycin, tigecycline, and polymyxin B—being investigated for the treatment of moderate-to-severe bacterial meningitis. The treatment regimen, led by investigator Yilong Wang, utilizes a novel delivery method called intracalvariosseous (ICO) injection in conjunction with standard intravenous (IV) administration. ICO injection involves continuous infusion into the calvarial bone marrow, which preclinical and clinical studies suggest can significantly enhance drug exposure within the central nervous system (CNS) compared to IV administration alone. This approach aims to overcome the blood-brain barrier limitations often encountered in treating severe CNS infections, particularly in patients who have shown an inadequate response to standard therapies. The FLAME trial is specifically designed to evaluate the efficacy and safety of this combined delivery route in patients with severe disease.