What is the coverage for atypical pneumonia caused by Mycobacterium intracellulare (M. intracellulare)?

From the Guidelines

For atypical pneumonia caused by Mycobacterium intracellulare (M. intracellulare), the recommended treatment regimen consists of a macrolide, such as clarithromycin or azithromycin, in combination with other medications, as macrolides are the only agents used for treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response 1.

Treatment Regimen

The treatment regimen typically includes a macrolide (clarithromycin 500mg twice daily or azithromycin 600mg daily) plus ethambutol 15mg/kg daily, and often rifampin 600mg daily or rifabutin 300mg daily. This three-drug combination therapy should typically be continued for at least 12 months after culture conversion to negative.

• The choice of macrolide is crucial, as clarithromycin and azithromycin have substantial in vitro and clinical activity against MAC, with the greatest potential advantage being their increased concentration in phagocytes and tissues, including lung 1.
• The addition of companion medications, such as streptomycin, ethambutol, and rifabutin or rifampin, is often necessary to achieve optimal treatment outcomes.
• For severe or extensive disease, an initial phase may include intravenous amikacin or streptomycin.

Treatment Duration and Monitoring

• Treatment duration is lengthy, usually 18-24 months total, because MAC organisms grow slowly and can develop resistance if treated inadequately.
• Regular monitoring of liver function, vision (due to ethambutol's potential ocular toxicity), and follow-up sputum cultures are essential during treatment.
• Patients should be advised about potential side effects including gastrointestinal disturbances, liver toxicity, and visual changes.

Rationale for Multidrug Approach

• The multidrug approach is necessary because MAC has a complex cell wall that makes it naturally resistant to many antibiotics, and combination therapy helps prevent the development of resistance during treatment.
• The development of clarithromycin-resistant MAC isolates is associated with microbiologic relapse, and patients with macrolide-resistant isolates do not respond favorably to standard macrolide-containing regimens 1.

From the FDA Drug Label

Clarithromycin has been shown to be active against most of the isolates of the following microorganisms both in vitroand in clinical infections [see Indications and Usage (1)] ... Mycobacterium avium complex (MAC) consisting of M. avium and M intracellulare ...

The coverage for atypical pneumonia caused by Mycobacterium intracellulare (M. intracellulare) is included in the drug's antimicrobial activity, as it is part of the Mycobacterium avium complex (MAC). Clarithromycin has been shown to be active against M. intracellulare in vitro and in clinical infections 2.

From the Research

Treatment Coverage for Atypical Pneumonia Caused by M. intracellulare

• The treatment for atypical pneumonia caused by Mycobacterium intracellulare (M. intracellulare) typically involves a combination of antibiotics, with the goal of converting sputum culture to negative and achieving clinical improvement 3, 4, 5, 6, 7.
• Recommended treatment regimens often include a macrolide, such as clarithromycin or azithromycin, in combination with other drugs like ethambutol, rifampicin, or streptomycin 3, 4, 5, 6, 7.
• The choice of treatment regimen should be based on species-specific resistance testing, and the duration of therapy is typically at least 12 months after conversion of the sputum culture 4.
• In some cases, treatment may need to be adjusted due to adverse effects or resistance, and alternative regimens may be considered 3, 5, 7.
• Surgical resection may be recommended in selected patients, particularly those with cavitation or pronounced nodular bronchiectatic disease 4.

Specific Treatment Regimens

• A regimen consisting of clarithromycin, ethambutol, and clofazimine was found to be successful in 20 of 30 patients (67%) with MAC lung disease 3.
• A combination of rifampicin, ethambutol, and macrolide (or isoniazid) is recommended for at least 12 months 4.
• Clarithromycin regimens have been shown to be effective in treating MAC lung disease, with 92% of patients converting their sputa to negative and 82% remaining culture-negative 5.
• A case report described a patient with pneumonia caused by M. avium complex who was successfully treated with clarithromycin alone after initial treatment with rifampicin, ethambutol, and clarithromycin was discontinued due to adverse effects 7.