By: Dana Weinstein, PharmD Candidate c/o 2022

             Mycobacterium avium complex (MAC) infection in humans is caused by two main species, Mycobacterium avium and Mycobacterium intracellulare. These species are difficult to differentiate and therefore are collectively referred to as Mycobacterium avium-intracellulare (MAI).¹ These acid-fast, atypical nontuberculosis mycobacterium (NTM) are the most common cause of lung disease in the U.S.² MAC is an easily-disseminated primarily pulmonary pathogen that is chiefly known to affect immunocompromised patients and is seen less often in immunocompetent hosts. Likely examples of MAC-susceptible patients would be those with AIDS (<10 CD₄⁺ T cells/μL), underlying lung disease, hairy cell leukemia, genetic TNF-alpha and IFN-gamma deficiency or immunosuppressive chemotherapy.¹

MAC has been isolated from certain sources including but not limited to, plumbing systems, household and hospital water supplies, bathrooms, hot tubs, aerosolized water, house dust, soil, birds, farm animals, and cigarette components.¹ Unlike in the setting of tuberculosis (TB), where secondary cases are often identified, when clusters of patients infected with similar isolates of MAC are found, the link is usually a common water source.³ Once the pathogen is inhaled into the respiratory tract and ingested into the gastrointestinal tract, it then translocates across mucosal epithelium, infects the resting macrophages in the lamina propria and spreads in the submucosal tissue. This directly translates to the fact that virtually all patients will present with a chronic or recurring cough leading to fatigue and a lower quality of life.^4,5 MAC is then carried to the local lymph nodes by the lymphatic system.¹ It can be disseminated into the spleen and bone marrow and potentially invade and colonize in intestinal cells if the species is gastric acid resistant, which appears to be a likely result in HIV-infected populations.³

Suspected MAC-infected pulmonary patients must have evident nodular or cavitary opacities on a chest radiograph and a least two positive sputum cultures or, in the absence of sputum specimens, at least one positive bronchoscopic specimen to meet the microbiologic criteria.³ Once the diagnosis is established, treatment regimen selection depends on susceptibility to macrolides; most MAC isolates, particularly in patients who have not been treated before, are macrolide-susceptible. Initial treatment of patients with MAC pulmonary disease is comprised of a three-drug regimen containing a macrolide, a rifamycin, and ethambutol (Myambutol®). For patients who have cavitary or advanced (severe) nodular bronchiectasis disease, a parenteral aminoglycoside is also often used in the initial phase of treatment.^4,5 The therapy recommendations for nontuberculous mycobacteria from the American Thoracic Society and Infectious Diseases Society of America are shown below: ⁴ (see PDF)

As shown in the table, regimen selection is initially based on severity and radiologic criteria. However, antibiotic susceptibility, macrolide resistance, drug interactions, and drug intolerance also play a key role in deciding optimal treatment administration. The macrolide of choice is typically azithromycin (Zithromax®) but can be substituted with clarithromycin (Biaxin®) for the renally impaired, although this drug tends to have worse tolerance. Rifampin (Rifadin®), the hallmark example drug for drug-drug interactions, can be replaced with rifabutin (Mycobutin®). In both cases of drug-intolerant patients or macrolide-resistant infections, patients are recommended to receive clofazimine (Lamprene®) or moxifloxacin (Avelox®) depending on antimicrobial susceptibility testing. Additionally, use of a parenteral aminoglycoside, such as amikacin, has been associated with augmenting treatment outcomes in patients with macrolide-resistant diseases.⁶

Once treatment is initiated, monitoring parameters include a complete blood count and a comprehensive metabolic panel for all patients. Patients receiving a macrolide, fluoroquinolone, or clofazimine should get an electrocardiogram to assess QT interval. An audiogram should be performed for patients receiving a macrolide or aminoglycoside and a visual acuity and color discrimination should be performed for patients receiving ethambutol.⁶ A successful patient response to therapy should be documented by sputum cultures negative for MAC. Therefore, acid-fact bacillus smears and cultures of sputum should be obtained monthly during therapy for pulmonary MAC disease to assess response. Patients should show clinical improvement within 3 to 6 months and should convert their sputum to negative within 12 months on macrolide-containing regimens.⁴

Ultimately, from a clinical and pharmaceutical standpoint, a MAC patient taking such a rigorous course of antibiotics likely brings into question the implementation of a probiotic. Probiotics help the body maintain a healthy community of microorganisms or help the body’s community of microorganisms return to a healthy condition after being disturbed.Although probiotics have an extensive history of apparently safe use in healthy people, few studies have looked at the safety of probiotics in detail. The risk of harmful effects from probiotics is greater in people with severe illnesses or compromised immune systems. Possible harmful effects of probiotics include infections, production of harmful substances by the probiotic microorganisms, and transfer of antibiotic resistance genes from probiotic microorganisms to other microorganisms in the digestive tract.⁷ As a team, the prescriber, the patient, and the pharmacist should work together to consider the decision and impact of implementing a probiotic in order to provide optimal treatment for each individual MAC patient.

Sources:

1. Koirala, J., 2020. Mycobacterium Avium Complex (MAC) (Mycobacterium Avium-Intracellulare [MAI]): Background, Pathophysiology, Etiology. [online] Emedicine.medscape.com. Available at: <https://emedicine.medscape.com/article/222664-overview#showall> [Accessed 14 June 2020].
2. MAC lung disease | American lung association. Lung.org. https://www.lung.org/lung-health-diseases/lung-disease-lookup/mac-lung-disease. Accessed July 11, 2020.
3. Daley CL. Mycobacterium avium Complex Disease. Microbiol Spectr. 2017;5(2): 10.1128/microbiolspec.TNMI7-0045-2017.
4. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous Mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367-416.
5. Charles L. Daley, Jonathan M. Iaccarino Jr., Christoph Lange, et al. Nontuberculous Mycobacterial (NTM) Diseases. IDSA Home. https://www.idsociety.org/practice-guideline/nontuberculous-mycobacterial-ntm-diseases/. Accessed July 31, 2020.
6. UpToDate. Uptodate.com. https://www.uptodate.com/contents/treatment-of-mycobacterium-avium-complex-pulmonary-infection-in-adults?search=treatment%20of%20mycobacterium%20avium%20complex%20pulmonary%20infection&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed June 17, 2020.
7. Probiotics: What you need to know. Nih.gov. https://www.nccih.nih.gov/health/probiotics-what-you-need-to-know. Accessed July 2, 2020.

Published by Rho Chi Post