Treatment of Nontuberculous Mycobacterial Pulmonary Disease: New Guideline

American Thoracic Society alongwith a number of infectious diseases societies (ERS, ESCMID, IDSA) has released guidelines onTreatment of Nontuberculous Mycobacterial Pulmonary Disease.

The guidelines have been published in the journal of Clinical Infectious Diseases.

The genus Mycobacterium consists of a diverse group of species and subspecies With the exception of Mycobacterium tuberculosis complex, Mycobacterium leprae complex, and Mycobacterium ulcerans the rest of the species are referred to as NTM, and they can be found throughout our environment. Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites.

This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM.

A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Main recommendations include-

Treatment of NTM Pulmonary Disease (Questions I–II)

I: Should patients with NTM pulmonary disease be treated with antimicrobial therapy or followed for evidence of progression ("watchful waiting")?

Recommendation

In patients who meet the diagnostic criteria for NTM pulmonary disease (Table 2), we suggest initiation of treatment rather than watchful waiting, especially in the context of positive acid-fast bacilli sputum smears and/or cavitary lung disease (conditional recommendation, very low certainty in estimates of effect).

II: Should patients with NTM pulmonary disease be treated empirically or based on in vitro drug susceptibility test results?

Recommendations

In patients with MAC pulmonary disease, we suggest susceptibility-based treatment for macrolides and amikacin over empiric therapy (conditional recommendation, very low certainty in estimates of effect).

In patients with M. kansasii pulmonary disease, we suggest susceptibility-based treatment for rifampicin over empiric therapy (conditional recommendation, very low certainty in estimates of effect).

In patients with M. xenopi pulmonary disease, the panel members felt there is insufficient evidence to make a recommendation for or against susceptibility-based treatment.

In patients with M. abscessus pulmonary disease we suggest susceptibility-based treatment for macrolides and amikacin over empiric therapy (conditional recommendation, very low certainty in estimates of effect). For macrolides, a 14-day incubation and/or sequencing of the erm(41) gene is required in order to evaluate for potential inducible macrolide resistance.

Mycobacterium avium Complex (Questions III–IX)

III: Should patients with macrolide-susceptible MAC pulmonary disease be treated with a 3-drug regimen with a macrolide or without a macrolide?

Recommendation

In patients with macrolide-susceptible MAC pulmonary disease, we recommend a 3-drug regimen that includes a macrolide over a 3-drug regimen without a macrolide (strong recommendation, very low certainty in estimates of effect).

IV: In patients with newly diagnosed macrolide-susceptible MAC pulmonary disease, should an azithromycin-based regimen or a clarithromycin-based regimen be used?

Recommendation

In patients with macrolide-susceptible MAC pulmonary disease we suggest azithromycin-based treatment regimens rather than clarithromycin-based regimens (conditional recommendation, very low certainty in estimates of effect).

V: Should patients with MAC pulmonary disease be treated with a parenteral amikacin or streptomycin-containing regimen or without a parenteral amikacin or streptomycin-containing regimen?

Recommendation

For patients with cavitary or advanced/severe bronchiectatic or macrolide-resistant MAC pulmonary disease, we suggest that parenteral amikacin or streptomycin be included in the initial treatment regimen (conditional recommendation, moderate certainty in estimates of effect).

VI: In patients with macrolide-susceptible MAC pulmonary disease, should a regimen with inhaled amikacin or a regimen without inhaled amikacin be used for treatment?

Recommendations

In patients with newly diagnosed MAC pulmonary disease, we suggest neither inhaled amikacin (parenteral formulation) nor amikacin liposome inhalation suspension (ALIS) be used as part of the initial treatment regimen (conditional recommendation, very low certainty in estimates of effect).

In patients with MAC pulmonary disease who have failed therapy after at least 6 months of guideline-based therapy, we recommend addition of ALIS to the treatment regimen rather than a standard oral regimen, only (strong recommendation, moderate certainty in estimates of effect).

VII: In patients with macrolide-susceptible MAC pulmonary disease, should a 3-drug or a 2-drug macrolide-containing regimen be used for treatment?

Recommendation

In patients with macrolide-susceptible MAC pulmonary disease, we suggest a treatment regimen with at least 3 drugs (including a macrolide and ethambutol) over a regimen with 2 drugs (a macrolide and ethambutol alone) (conditional recommendation, very low certainty in estimates of effect).

VIII: In patients with macrolide susceptible MAC pulmonary disease, should a daily or a 3-times weekly macrolide-based regimen be used for treatment?

Recommendations

In patients with noncavitary nodular/bronchiectatic macrolide-susceptible MAC pulmonary disease, we suggest a 3 times per week macrolide-based regimen rather than a daily macrolide-based regimen (conditional recommendation, very low certainty in estimates of effect).

In patients with cavitary or severe/advanced nondular bronchiectatic macrolide-susceptible MAC pulmonary disease we suggest a daily macrolide-based regimen rather than 3 times per week macrolide-based regimen (conditional recommendation, very low certainty in estimates of effect).

IX: In patients with macrolide-susceptible MAC pulmonary disease, should patients be treated with <12 months of treatment after culture negativity or ≥12 months of treatment after culture negativity?

Recommendation

We suggest that patients with macrolide-susceptible MAC pulmonary disease receive treatment for at least 12 months after culture conversion (conditional recommendation, very low certainty in estimates of effect).

Mycobacterium kansasii (Questions X–XIV)

X: In patients with rifampcin-susceptible M. kansasii pulmonary disease, should an isoniazid-containing regimen or a macrolide-containing regimen be used for treatment?

Recommendation

In patients with rifampicin-susceptible M. kansasii pulmonary disease, we suggest a regimen of rifampicin, ethambutol, and either isoniazid or macrolide (conditional recommendation, very low certainty in estimates of effect).

XI: In patients with rifampicin-susceptible M. kansasii pulmonary disease, should parenteral amikacin or streptomycin be included in the treatment regimen?

Recommendation

We suggest that neither parenteral amikacin nor streptomycin be used routinely for treating patients with M. kansasii pulmonary disease (strong recommendation, very low certainty in estimates of effect).

XII: In patients with rifampicin-susceptible M. kansasii pulmonary disease, should a treatment regimen that includes a fluoroquinolone or a regimen without a fluoroquinolone be used?

Recommendations

In patients with rifampicin-susceptible M. kansasii pulmonary disease, we suggest using a regimen of rifampicin, ethambutol, and either isoniazid or macrolide instead of a fluoroquinolone (conditional recommendation, very low certainty in estimates of effect).

In patients with rifampicin-resistant M. kansasii or intolerance to one of the first-line antibiotics we suggest a fluoroquinolone (eg, moxifloxacin) be used as part of a second-line regimen (conditional recommendation, very low certainty in estimates of effect).

XIII: In patients with rifampicin-susceptible M. kansasii pulmonary disease, should a 3 times per week or daily treatment regimen be used?

Recommendations

In patients with noncavitary nodular/bronchiectatic M. kansasii pulmonary disease treated with a rifampicin, ethambutol, and macrolide regimen, we suggest either daily or 3 times weekly treatment (conditional recommendation, very low certainty in estimates of effect)

In patients with cavitary M. kansasii pulmonary disease treated with a rifampicin, ethambutol, and macrolide-based regimen, we suggest daily treatment instead of 3 times weekly treatment (conditional recommendation, very low certainty in estimates of effect).

In all patients with M. kansasii pulmonary disease treated with an isoniazid, ethambutol, and rifampicin regimen, we suggest treatment be given daily instead of 3 times weekly (conditional recommendation, very low certainty in estimates of effect).

XIV: In patients with rifampicin susceptible M. kansasii pulmonary disease, should treatment be continued for <12 months or ≥12 months?

Recommendation

We suggest that patients with rifampin susceptible M. kansasii pulmonary disease be treated for at least 12 months (conditional recommendation, very low certainty in estimates of effect).

Mycobacterium xenopi (Questions XV–XVIII)

XV: In patients with M. xenopi pulmonary disease, should a treatment regimen that includes a fluoroquinolone or a regimen without a fluoroquinolone be used?

Recommendation

In patients with M. xenopi pulmonary disease, we suggest using a multidrug treatment regimen that includes moxifloxacin or macrolide (conditional recommendation, low certainty in estimates of effect).

XVI: In patients with M. xenopi pulmonary disease, should a 2-, 3-, or 4-drug regimen be used for treatment?

Recommendation

In patients with M. xenopi pulmonary disease, we suggest a daily regimen that includes at least 3 drugs: rifampicin, ethambutol, and either a macrolide and/or a fluoroquinolone (eg, moxifloxacin) (conditional recommendation, very low certainty in estimates of effect).

Remarks:

Given the high mortality associated with M. xenopi disease, the panel members felt the large risk of treatment failure with a 2-drug regimen warranted at least a 3-drug treatment regimen. However, the absence of universal access to moxifloxacin and the small amount of data for other fluoroquinolones has to be considered when choosing a regimen.

XVII: In patients with M. xenopi pulmonary disease, should parenteral amikacin or streptomycin be included in the treatment regimen?

In patients with cavitary or advanced/severe bronchiectatic M. xenopi pulmonary disease, we suggest adding parenteral amikacin to the treatment regimen and obtaining expert consultation (conditional recommendation, very low certainty in estimates of effect).

XVIII: In patients with M. xenopi pulmonary disease, should treatment be continued for <12 months or ≥12 months after culture conversion?

In patients with M. xenopi pulmonary disease, we suggest that treatment be continued for at least 12 months beyond culture conversion (conditional recommendation, very low certainty in estimates of effect).

Mycobacterium abscessus (Questions XIX–XXI)

XIX: In patients with M. abscessus pulmonary disease, should a macrolide-based regimen or a regimen without a macrolide be used for treatment?

Recommendations

In patients with M. abscessus pulmonary disease caused by strains without inducible or mutational resistance, we recommend a macrolide-containing multidrug treatment regimen (strong recommendation, very low certainty in estimates of effect).

In patients with M. abscessus pulmonary disease caused by strains with inducible or mutational macrolide resistance, we suggest a macrolide-containing regimen if the drug is being used for its immunomodulatory properties although the macrolide is not counted as an active drug in the multidrug regimen (conditional recommendation, very low certainty in estimates of effect).

XX: In patients with M. abscessus complex pulmonary disease, how many antibiotics should be included within multidrug regimens?

Recommendation

In patients with M. abscessus pulmonary disease, we suggest a multidrug regimen that includes at least 3 active drugs (guided by in vitro susceptibility) in the initial phase of treatment (conditional recommendation, very low certainty in estimates of effect).

XXI: In patients with M. abscessus pulmonary disease, should shorter or longer duration therapy be used for treatment?

Recommendation

In patients with M. abscessus pulmonary disease, we suggest that either a shorter or longer treatment regimen be used and expert consultation obtained (conditional recommendation for either the intervention or the comparison, very low certainty in estimates of effect).

Surgical Resection (Question XXII)

XXII: Should surgery plus medical therapy or medical therapy alone be used to treat NTM pulmonary disease?

Recommendation

In selected patients with NTM pulmonary disease, we suggest surgical resection as an adjuvant to medical therapy after expert consultation (conditional recommendation, very low certainty in estimates of effect).

For further reference log on to:

Clinical Infectious Diseases, ciaa241, https://doi.org/10.1093/cid/ciaa241