From the Research
For patients with Mendelian Susceptibility to Mycobacterial Disease (MSMD), antimycobacterial treatment should be initiated promptly upon diagnosis with a multidrug regimen, as recommended by the most recent study 1. The recommended initial treatment includes isoniazid (10-15 mg/kg/day, maximum 300 mg daily), rifampin (10-20 mg/kg/day, maximum 600 mg daily), ethambutol (15-25 mg/kg/day), and clarithromycin (15-30 mg/kg/day in two divided doses, maximum 1 g daily) or azithromycin (10-12 mg/kg/day, maximum 500 mg daily). This intensive phase should continue for 1-2 months, followed by a continuation phase with isoniazid and rifampin for at least 12 months total, though treatment duration may extend to 18-24 months depending on clinical response, as suggested by 2. Some key points to consider when treating MSMD patients include:
- Regular monitoring of liver function tests, visual acuity (for ethambutol), and therapeutic drug levels is essential, as highlighted in 3.
- Adjunctive interferon-gamma therapy (50 μg/m² subcutaneously three times weekly) may be beneficial for patients with specific genetic defects affecting the IFN-γ pathway, as noted in 4.
- Treatment should be tailored to antimicrobial susceptibility testing results when available, as recommended by 5. MSMD patients require this aggressive approach because their genetic defects in the IL-12/IFN-γ pathway impair macrophage activation and granuloma formation, making them particularly vulnerable to mycobacterial infections that may be difficult to eradicate without prolonged combination therapy, as explained in 1.