Nontuberculous Mycobacterial Pulmonary Disease

What is the approach to management of NTM pulmonary disease?

The correlation of symptoms with radiographic and microbiologic evidence is essential to categorize the disease and determine the need for therapy. Making the diagnosis of NTM lung disease does not necessitate the institution of therapy. The decision to treat should be weighed against potential risks and benefits to the individual patient based on symptomatic, radiographic, and microbiologic criteria, as well as underlying systemic or pulmonary immune status. In the absence of evidence of clinical, radiologic, or mycobacterial progression of disease, pursuing airway clearance therapy and clinical surveillance without initiating specific anti-MAC therapy is a reasonable option.¹¹ Identifying the sustained presence of NTM infection, especially MAC, in a patient with underlying clinical and radiographic evidence of bronchiectasis is of value in determining comprehensive treatment and management strategies. Close observation is indicated if the decision not to treat is made. If treatment is initiated, comprehensive management includes long-term follow-up with periodic bacteriologic surveillance, watching for drug toxicity and drug-drug interactions, ensuring adherence and compliance to treatment, and managing comorbidity.

The Bronchiectasis Severity Index is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations and can be used to evaluate the need for specific treatment.30 The index is based on dyspnea score, lung function tests, colonization of pathogens, and extent of disease.

Case 1 Continued

After approximately 2 months of observation and symptomatic treatment, without specific antibiotic therapy, the patient’s symptoms continue. She now develops intermittent hemoptysis. Repeat sputum studies reveal moderate growth of M. avium. A follow-up CT scan shows progression of disease, with an increase in the tree-in-bud pattern (Figure 3).

What treatment protocols are recommended for MAC pulmonary disease?

As per the ATS/IDSA statement, macrolides are the mainstay of treatment for pulmonary MAC disease.¹¹ Macrolides achieve an increased concentration in the lung, and when used for treatment of pulmonary MAC disease, there is a strong correlation between in vitro susceptibility, in vivo (clinical) response, and the immunomodulating effects of macrolides.^31,32 Macrolide-containing regimens have demonstrated efficacy in patients with MAC pulmonary disease^33,34; however, macrolide monotherapy should be avoided to prevent the development of resistance.

At the outset, it is critical to establish the objective criteria for determining response and to ensure that the patient understands the goals of the treatment and expectations of the treatment plan. Moreover, experts suggest that due to the possibility of drug intolerance, side effects, and the need for prolonged therapy, a “step ladder” ramping up approach to treatment could be adopted, with gradual introduction of therapy within a short time period; this approach may improve compliance and adherence to treatment.¹¹ If this approach is used, the doses may have to be divided. Patients who are unable to tolerate daily medications, even with dosage adjustment, should be tried on an intermittent treatment regimen. Older female patients frequently require gradual introduction of medications (ie, 1 medication added to the regimen every 1 to 2 weeks) to evaluate tolerance to each medication and medication dose.¹¹ Commonly encountered adverse effects of NTM treatment include intolerance to clarithromycin due to gastrointestinal problems, low body mass index, or age older than 70 years.

After determining that the patient requires therapy, the standard recommended treatment for MAC pulmonary disease includes the following: for most patients with nodular/bronchiectasis disease, a thrice-weekly regimen of clarithromycin (1000 mg) or azithromycin (500 mg), rifampin (600 mg), and ethambutol (25 mg/kg) is recommended. For patients with cavitary MAC pulmonary disease or severe nodular/bronchiectasis disease, the guidelines recommend a daily regimen of clarithromycin (500-1000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg), with consideration of intravenous (IV) amikacin 3 times/week early in therapy (Table 2).¹¹

The treatment of MAC hypersensitivity-like disease speaks to the controversy of whether this is an inflammatory process, infectious process, or a combination of inflammation and infection. Avoidance of exposure is the mainstay of management. In some cases, steroids are used with or without a short course of anti-MAC therapy (ie, clarithromycin or azithromycin with rifampin and ethambutol).

Prophylaxis for disseminated MAC disease should be given to adults with HIV infection who have a CD4+ count less than 50 cells/μL. Azithromycin 1200 mg/week or clarithromycin 1000 mg/day has proven efficacy, and rifabutin 300 mg/day is also effective but less well tolerated. Rifabutin is more active in vitro against MAC than rifampin, and is used in HIV-positive patients because of drug-drug interaction between antiretroviral drugs and rifampin.

Continue to: Case 1 Continued