by Dr. William Chamberlin

Nobody knows the optimum drug regimen to treat MAP. However, there are therapeutic principles that should be considered:

 

1. Mycobacteria evolve. Resistant clones will emerge with single drug coverage. Therefore, multiple antibiotics should be administered.
2. Mycobacteria switch their metabolism/morphology to a functionally more survivable state when stressed. Whether MAP forms cysts, becomes metabolically dormant or enhances its survival by assuming a cell-wall-deficient morphology in biofilms are all possibilities requiring further research. Nevertheless, properly chosen antibiotics need to be given for extended periods.
3. Crohn’s disease is associated with innate immune deficiencies. Immune deficiencies predispose to microbial infections. Pathogenic mycobacteria exploit the immune deficiencies associated with Crohn’s disease identified by Genome Wide Association Studies.Optimum drug therapies for Crohn’s disease will include methods to enhance innate immunity.

Commentary on the efficacy of AMAT regimens is problematic without a method to measure whether treatment actually results in a reduction in bacterial infection. (Fortunately, advances in culture technique and fluorescent monoclonal antibody assays may soon solve this problem. Please view the videos from the August symposium by John Aitken and Dr. Amy Hermon-Taylor.) At this point any assumptions about AMAT efficacy are based on clinical improvement in patients.  Treatment regimens are based on experience with other Mycobacterium Avium Complex species.

My approach is as follows:

AMAT is given daily for three to six months as a trial. If improvement is noted then it is continued for another 2 to 3 years. We truly don’t know how long to continue treatment. Regimens with reduced frequency of dosing, altered drug regimens, etc. all need to be explored. If there is absolutely no improvement then the decision is made to stop treatment and return to the conventional approaches (which usually have already been tried and found wanting.)

AMAT regimens that have been used are described below. As with any infection, optimum treatments will undoubtedly shift over time as different bacterial clones evolve.

1. AZITHROMYCIN, RIFABUTIN, ETHAMBUTOL: Daily weight based dosing using standard recommendations. This regimen is recommended for “MAC Atypical Mycobacteria” by many. I have found it to be successful.
2. CLARITHROMYCIN, RIFABUTIN, CLOFAZIMINE: This regimen was developed by Dr. Borody and is licensed to RedHill Biopharma. There is undoubtedly more experience using this combination of antibiotics than with any other.
3. CLARITHROMYCIN, RIFAMPIN, LEVOFLOXACIN: I usually start patients on this regimen due to its lower expense and possibly fewer side effects. Standard dosing applies.
4. Other combinations are likely to be effective. As a general rule, I want to include either Azithromycin or Clarithromycin, either Rifabutin or Rifampin, plus a third drug known to be active against non-tuberculosis mycobacteria. These other drugs include Ethambutol, Metronidazole, Moxifloxicin, Ciprofloxacin and undoubtedly others.

To repeat: the optimum dosing, frequency and duration of treatment is yet to be determined.  Hopefully new and better drugs will be discovered.

One last comment for physicians new to the field: Ciprofloxacin and Metronidazole are accepted drugs used to treat Crohn’s disease. Both are active against MAP. Hypotheses that these drugs work through their effects on the microbiota are just that – hypotheses. Successful outcomes are often presaged by a flu-like syndrome after starting antibiotics thought to be an immune reconstitution syndrome.

Recommended Adult Dosages:

• Clarithromycin 500 mg twice daily
• Azithromycin 250 mg daily
• Rifampin 300 mg twice daily
• Rifabutin 150 mg twice daily
• Ethambutol  800 to 1200 mg daily
• Levofloxacin 500 mg daily
• Ciprofloxacin 500 mg twice daily
• Clofazimine 100 mg daily