333. Comparative Efficacy of Rifamycin-containing Regimens in a Murine Model of Tuberculous Meningitis
Abstract
Abstract Background Tuberculous meningitis (TB meningitis), the most severe form of tuberculosis (TB), is associated with high mortality and neurological sequelae. Standard therapy includes rifampin, a key drug for pulmonary TB; however, its efficacy in TB meningitis is hampered by poor blood-brain barrier penetration, often resulting in subtherapeutic concentrations. While alternative rifamycins like rifapentine and rifabutin exhibit distinct pharmacokinetic advantages, including reduced cytochrome P450 induction, and have been evaluated for pulmonary TB, their utility in TB meningitis remains unexplored.Figure 1.Evaluation of rifamycin-containing regimens in the mouse model of TB meningitis.(A) Mice were infected intraventricularly via Burr hole using a syringe and stereotaxic instrument, treatment were initiated two weeks after (designated as day 0) and continued for six weeks. Mice were randomly allocated to receive multi-drug regimens HRZ, HRZMx, HPZMx, or HRbZ. Isoniazid (10 mg/kg/day), pyrazinamide (150 mg/kg/day), rifampin (10 mg/kg/day), rifapentine (20 mg/kg/day), rifabutin (10 mg/kg/day), and moxifloxacin (100 mg/kg/day divided twice daily) were administered via oral gavage. Mouse dosing was utilized to match the standard human equipotent dosing: isoniazid (10 mg/kg/day), pyrazinamide (25 mg/kg/day), rifampin (10 mg/kg/day), rifapentine (1200 mg), rifabutin (300 mg), and moxifloxacin (400 mg). All regimens received adjunctive dexamethasone via intraperitoneal…
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