From the Guidelines
Antimycobacterial therapy should be initiated promptly in patients with immunodeficiency due to Mendelian inheritance, with clarithromycin as the preferred first agent, due to its extensive study and association with rapid clearance of MAC from the blood 1. When considering the treatment of patients with immunodeficiency due to Mendelian inheritance, it is crucial to prioritize a regimen that prevents or delays the emergence of resistance.
- The initial treatment should consist of two or more antimycobacterial drugs, with clarithromycin being the preferred first agent, as it has been studied more extensively than azithromycin in patients with AIDS and appears to be associated with more rapid clearance of MAC from the blood 1.
- Azithromycin can be substituted for clarithromycin when drug interactions or clarithromycin intolerance preclude the use of clarithromycin, as recommended by the CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America 1.
- Testing MAC isolates for susceptibility to clarithromycin or azithromycin is recommended for all patients, to ensure the most effective treatment regimen 1. The treatment regimen should be tailored to the individual patient's needs, taking into account the severity of the infection, potential drug interactions, and the patient's overall health status.
- Regular monitoring for drug toxicity is essential, including visual acuity for ethambutol and liver function tests for rifampin, to minimize the risk of adverse effects.
- The antimycobacterial regimen compensates for the immune deficit by directly targeting the mycobacteria, and adjunctive interferon-gamma therapy may be beneficial in patients with specific pathway defects, as part of a comprehensive treatment plan.
From the Research
Role of Starting Antimycobacterial Agent
The role of starting antimycobacterial agents in patients with immunodeficiency due to Mendelian inheritance is crucial in managing mycobacterial infections.
- Patients with primary immunodeficiencies (PID) are highly susceptible to mycobacterial infections, including Mycobacterium tuberculosis, Bacille Calmette-Guerin, and non-tuberculosis mycobacterium (NTM) 2.
- Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to infections caused by intracellular pathogens, such as mycobacteria, due to impaired IFN-γ immunity 3.
- The choice of starting antimycobacterial agent depends on the specific type of mycobacterial infection and the patient's underlying immunodeficiency.
Genetic Basis of Immunodeficiency
- MSMD is associated with mutations in 18 different genes, including those involved in IFN-γ-dependent immunity 3, 4.
- These genetic defects can impair the production of or response to IFN-γ, leading to increased susceptibility to mycobacterial infections 4.
- X-linked recessive forms of MSMD have been described, caused by mutations in the NEMO and CYBB genes 5.
Clinical Features and Treatment
- Patients with MSMD may display a range of clinical features, including multifocal osteomyelitis, and may be prone to other infections such as salmonellosis and candidiasis 3, 4.
- The treatment of mycobacterial infections in patients with immunodeficiency due to Mendelian inheritance typically involves the use of antimycobacterial agents, such as rifampicin and isoniazid 2.
- The choice of treatment regimen should be guided by the specific type of mycobacterial infection and the patient's underlying immunodeficiency, as well as the results of drug susceptibility testing 2.