Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

pulmonary MAC

1st line – combination antimycobacterial therapy

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ONGOING
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pulmonary MAC
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mild to moderate nodular bronchiectatic disease
1st line – 

combination antimycobacterial therapy

For Mycobacterium avium complex (MAC) pulmonary disease, treatment recommendations take into consideration the severity of disease as well as the radiographic appearance.

For mild to moderate nodular bronchiectatic disease, intermittent, three-times-weekly dosing with a macrolide (azithromycin or clarithromycin) plus ethambutol plus rifampin or rifabutin is recommended. Azithromycin has fewer drug interactions and may be better tolerated than clarithromycin.[40][41]​ Macrolides have rarely been associated with altered cardiac conduction (e.g., QT interval prolongation, arrhythmias including torsades de pointes).

Patients will require treatment until sputum cultures are consecutively negative for at least 12 months.[40]

Older patients or patients who require long-term (6 months or longer) therapy may require lower doses.

Treatment of macrolide-resistant MAC disease should only be done in consultation with a specialist, as management of these patients is complex. Guidelines suggest that extensive use of additional agents before referral to a specialist may compromise the patient's chance for an optimal therapeutic response; therefore, prompt referral is important.[40]

Primary options

azithromycin: 500 mg orally three times weekly

or

clarithromycin: 1000 mg orally (immediate-release) three times weekly

More

-- AND --

ethambutol: 25 mg/kg orally three times weekly

-- AND --

rifampin: 600 mg orally three times weekly

or

rifabutin: 300 mg orally three times weekly

Consider – lobectomy/pneumonectomy

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ONGOING
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pulmonary MAC
|
mild to moderate nodular bronchiectatic disease
Consider – 

lobectomy/pneumonectomy

Treatment recommended for SOME patients in selected patient group

May be considered in patients with localized disease, especially upper lobe cavitary disease; patients who failed to convert the sputum culture to negative after 6 months of continuous medical therapy; or patients who cannot tolerate medical therapy.

1st line – combination antimycobacterial therapy

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ONGOING
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pulmonary MAC
|
cavitary disease
1st line – 

combination antimycobacterial therapy

For Mycobacterium avium complex (MAC) pulmonary disease, treatment recommendations take into consideration the severity of disease as well as the radiographic appearance.

For patients with cavitary disease, daily therapy with a macrolide (azithromycin or clarithromycin) plus ethambutol plus rifampin or rifabutin is recommended. Azithromycin has fewer drug interactions and may be better tolerated than clarithromycin.[40][41]​ Macrolides have rarely been associated with altered cardiac conduction (e.g., QT interval prolongation, arrhythmias including torsades de pointes).

Current US guidelines also recommend the addition of a parenteral aminoglycoside (amikacin or streptomycin) for the initial 2 to 3 months in cavitary disease. These may be given three times weekly.[40][41]​ Aminoglycosides are associated with ototoxicity and nephrotoxicity, and monitoring of serum drug levels and renal function is recommended.

Patients will require treatment until sputum cultures are consecutively negative for at least 12 months.[40]

Older patients or patients who require long-term (6 months or longer) therapy may require lower doses.

Treatment of macrolide-resistant MAC disease should only be done in consultation with a specialist, as management of these patients is complex. Guidelines suggest that extensive use of additional agents before referral to a specialist may compromise the patient's chance for an optimal therapeutic response; therefore, prompt referral is important.[40]

Primary options

azithromycin: 250-500 mg orally once daily

or

clarithromycin: 500 mg orally (immediate-release) twice daily

-- AND --

ethambutol: 15 mg/kg orally once daily

-- AND --

rifampin: 10 mg/kg orally once daily, maximum 600 mg/day

or

rifabutin: 150-300 mg orally once daily

More

-- AND --

streptomycin: 10-15 mg/kg intravenously/intramuscularly once daily; or 15-25 mg/kg intravenously/intramuscularly three times weekly; adjust dose according to serum streptomycin level

or

amikacin: 10-15 mg/kg intravenously once daily; or 15-25 mg/kg intravenously three times weekly; adjust dose according to serum amikacin level

Consider – lobectomy/pneumonectomy

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ONGOING
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pulmonary MAC
|
cavitary disease
Consider – 

lobectomy/pneumonectomy

Treatment recommended for SOME patients in selected patient group

May be considered in patients with localized disease, especially upper lobe cavitary disease; patients who failed to convert the sputum culture to negative after 6 months of continuous medical therapy; or patients who cannot tolerate medical therapy.

1st line – combination antimycobacterial therapy

Back
ONGOING
|
pulmonary MAC
|
advanced (severe) disease or previously treated disease
1st line – 

combination antimycobacterial therapy

For Mycobacterium avium complex (MAC) pulmonary disease, treatment recommendations take into consideration the severity of disease as well as the radiographic appearance.

For patients with advanced (severe) disease, daily therapy with a macrolide (azithromycin or clarithromycin) plus ethambutol plus rifampin or rifabutin is recommended. Azithromycin has fewer drug interactions and may be better tolerated than clarithromycin. Macrolides have rarely been associated with altered cardiac conduction (e.g., QT interval prolongation, arrhythmias including torsades de pointes). For patients with advanced (severe) disease, or where prior drug therapy has failed, the addition of a parenteral aminoglycoside (amikacin or streptomycin) to the regimen for the first 2 to 3 months of combination antimycobacterial therapy should be considered. These drugs may be given three times weekly.[40][41]​ Aminoglycosides are associated with ototoxicity and nephrotoxicity, and monitoring of serum drug levels and renal function is recommended.

Treatment is continued until sputum cultures are consecutively negative for at least 12 months.

Older patients or patients who require long-term (6 months or longer) therapy may require lower doses.

Treatment of macrolide-resistant MAC disease should only be done in consultation with a specialist, as management of these patients is complex. Guidelines suggest that extensive use of additional agents before referral to a specialist may compromise the patient's chance for an optimal therapeutic response; therefore, prompt referral is important.[40]

Primary options

azithromycin: 250-500 mg orally once daily

or

clarithromycin: 500 mg orally (immediate-release) twice daily

-- AND --

ethambutol: 15 mg/kg orally once daily

-- AND --

rifampin: 10 mg/kg orally once daily, maximum 600 mg/day

or

rifabutin: 150-300 mg orally once daily

More

-- AND --

streptomycin: 10-15 mg/kg intravenously/intramuscularly once daily; or 15-25 mg/kg intravenously/intramuscularly three times weekly; adjust dose according to serum streptomycin level

or

amikacin: 10-15 mg/kg intravenously once daily; or 15-25 mg/kg intravenously three times weekly; adjust dose according to serum amikacin level

Consider – amikacin liposomal inhalation

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ONGOING
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pulmonary MAC
|
advanced (severe) disease or previously treated disease
Consider – 

amikacin liposomal inhalation

Treatment recommended for SOME patients in selected patient group

If patients have not achieved negative sputum cultures after a minimum of 6 consecutive months of guideline-based therapy, amikacin liposomal inhalation may be added to the treatment regimen (i.e., daily therapy with azithromycin or clarithromycin plus ethambutol plus rifampin or rifabutin as per above).[40]

Primary options

amikacin liposomal inhaled: 590 mg inhaled via nebulizer once daily

Consider – lobectomy/pneumonectomy

Back
ONGOING
|
pulmonary MAC
|
advanced (severe) disease or previously treated disease
Consider – 

lobectomy/pneumonectomy

Treatment recommended for SOME patients in selected patient group

May be considered in patients with localized disease, especially upper lobe cavitary disease; patients who failed to convert the sputum culture to negative after 6 months of continuous medical therapy; or patients who cannot tolerate medical therapy.

disseminated MAC

1st line – combination antimycobacterial therapy

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ONGOING
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disseminated MAC
1st line – 

combination antimycobacterial therapy

A macrolide (clarithromycin or azithromycin) plus ethambutol form the cornerstone of therapy for disseminated infection. Azithromycin can be substituted for clarithromycin where drug interactions and/or tolerability are an issue.[8]

Macrolides have rarely been associated with altered cardiac conduction (e.g., QT interval prolongation, arrhythmias including torsades de pointes).

Treatment of macrolide-resistant Mycobacterium avium complex disease should only be done in consultation with a specialist, as management of these patients is complex. Guidelines suggest that extensive use of additional agents before referral to a specialist may compromise the patient's chance for an optimal therapeutic response; therefore, prompt referral is important.[30]

Primary options

azithromycin: 500-600 mg orally once daily

or

clarithromycin: 500 mg orally (immediate-release) twice daily

-- AND --

ethambutol: 15 mg/kg orally once daily

Plus – add third or fourth drug to combination regimen

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ONGOING
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disseminated MAC
|
advanced immunosuppression
Plus – 

add third or fourth drug to combination regimen

Treatment recommended for ALL patients in selected patient group

A third or fourth drug may be added in patients with advanced immunosuppression (CD4 count <50 cells/microliter) or high mycobacterial load, or in the absence of effective antiretroviral therapy (ART). Options for a third or fourth drug may include rifabutin, a fluoroquinolone (e.g., levofloxacin or moxifloxacin), or an injectable aminoglycoside (e.g., amikacin or streptomycin).[8]

Aminoglycosides are associated with ototoxicity and nephrotoxicity, and monitoring of serum drug levels and renal function is recommended.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. These include, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[42]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Primary options

rifabutin: 300 mg orally once daily

OR

levofloxacin: 500 mg orally once daily

OR

moxifloxacin: 400 mg orally once daily

OR

amikacin: 10-15 mg/kg intravenously once daily, adjust dose according to serum amikacin level

OR

streptomycin: 10-15 mg/kg intravenously/intramuscularly once daily, adjust dose according to serum streptomycin level

Consider – antiretroviral therapy

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ONGOING
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disseminated MAC
|
advanced immunosuppression
Consider – 

antiretroviral therapy

Treatment recommended for SOME patients in selected patient group

Initiate or continue antiretroviral therapy (ART) in HIV-infected patients.[8]​ See HIV infection.

MAC lymphadenitis

1st line – surgical excision

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ONGOING
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MAC lymphadenitis
|
localized disease
1st line – 

surgical excision

Complete lymph node excision results in complete resolution of disease reported in 80% to 96% of patients.[43]

1st line – combination antimycobacterial therapy

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ONGOING
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MAC lymphadenitis
|
extensive disease; poor surgical response
1st line – 

combination antimycobacterial therapy

If extensive disease, or poor response to surgical therapy, antimycobacterial therapy (e.g., clarithromycin plus rifampin plus ethambutol) can be initiated.[30]

Macrolides such as clarithromycin have rarely been associated with altered cardiac conduction (e.g., QT interval prolongation, arrhythmias including torsades de pointes).

Treatment of macrolide-resistant Mycobacterium avium complex disease should only be done in consultation with a specialist, as management of these patients is complex. Guidelines suggest that extensive use of additional agents before referral to a specialist may compromise the patient's chance for an optimal therapeutic response; therefore, prompt referral is important.[30]

Primary options

clarithromycin: 500 mg orally (immediate-release) twice daily

and

rifampin: 600 mg orally once daily

and

ethambutol: 15 mg/kg orally once daily

MAC hypersensitivity pneumonitis

1st line – corticosteroid

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ONGOING
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MAC hypersensitivity pneumonitis
1st line – 

corticosteroid

Use of corticosteroids may shorten recovery time and improve gas exchange. Prednisone tapered over 4-8 weeks is the treatment of choice.

Primary options

prednisone: 1-2 mg/kg/day orally

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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