Mycobacterium Avium-Intracellulare Medication
- Author: Janak Koirala, MD, MPH, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD more...
The drugs used most often for treatment of Mycobacterium avium complex (MAC) infection include a macrolide (eg, clarithromycin, azithromycin), ethambutol, and a rifamycin (eg, rifabutin, rifampin).
Clarithromycin or azithromycin in combination with ethambutol and rifabutin are the first-choice drugs. Combination therapy is important for enhancing efficacy and preventing resistance.
Alternatively, clofazimine, streptomycin, amikacin, or a fluoroquinolone may be used as a substitute for one of the first-line agents. Streptomycin has been shown to be useful in cavitary lung disease. Amikacin is used for refractory cases.
Clofazimine should be avoided in patients with disseminated MAC (DMAC) infection because of worse outcomes compared with other regimens. The combination of a macrolide with a fluoroquinolone should be avoided, as they show antagonism in infections with some strains of MAC, and their combination has been associated with the development of resistance.
The duration of treatment is not established. In general, patients with MAC pulmonary infection should be treated for a minimum of 1 year or until 12 months after sputum stains are negative for MAC. The rate of relapse is high, especially if the treatment duration is too short. Long-term treatment, however, is harder to tolerate and increases the likelihood of adverse effects.
Macrolides are likely to interact with drugs metabolized in the liver.
Ethambutol may cause optic neuritis and blindness, especially in patients with coexisting renal dysfunction.
Rifampin and rifabutin may decrease the effectiveness of contraceptives and other drugs metabolized in the liver. Advise patients of this potential effect. Rifabutin is also known to cause uveitis, for which patients need regular eye examinations.
Failing to offer prophylaxis to patients with HIV with a CD4+ lymphocyte count of below 50 cells/µL may lead to development of DMAC infection.
Empiric antimicrobial therapy must be comprehensive.
Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer RNA (tRNA) from ribosomes, arresting RNA-dependent protein synthesis.
Azithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, arresting RNA-dependent protein synthesis.
Ethambutol impairs cell metabolism by inhibiting synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been administered previously.
Rifabutin is an ansamycin antibiotic derived from rifamycin S. It inhibits DNA-dependent RNA polymerase, preventing chain initiation, in susceptible bacterial strains. If GI upset occurs, administer dose twice daily with food.
Useful in combination with other drugs, rifampin inhibits bacterial DNA-dependent RNA polymerase.
Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. It is used in combination with other agents in the treatment of MAC.
Levofloxacin is a fluorinated quinolone that inhibits bacterial DNA gyrase and topoisomerase IV.
This agent inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.
Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes, blocks the recognition step in protein synthesis, and causes growth inhibition. Use the patient's ideal body weight (IBW) for dosage calculation.
Streptomycin acts by binding to the 30S ribosomal subunit and interferes with translational proofreading, which result in an inhibition of protein synthesis. It is used in combination with other drugs in the treatment of MAC.
Clofazimine is a lipophilic rhimophenazine dye that inhibits template function of DNA by binding to it. It is weakly bactericidal and has anti-inflammatory effects. This agent was originally developed to treat tuberculosis. Although its mechanism of action is unclear, it seems to exert its main effect upon neutrophils and monocytes in a variety of ways (eg, stimulating phagocytosis and release of lysosomal enzymes).
Clofazimine is absorbed orally, accumulates in tissues, and has half-life >70 d. In addition to daily dose, loading dose of 300 mg once a month (under supervision) is given in leprosy control programs. This approach maintains optimal amount of drug in body tissue, even if the patient occasionally misses daily dose.
This agent was discontinued from the United States market in 2005, but is now available as orphan product.
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