

Treatment of Nontuberculous Mycobacterial Pulmonary Disease
Introduction
Introduction
- 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.
- The Panel recommends that clinical, radiographic, and microbiologic data be collected to monitor response to therapy, expectations be set for the patient's progress and patient cooperation be enlisted in identifying adverse drug reactions. (See full text guideline for further details)
Diagnosis
Diagnosis
Table 1. Clinical, Radiographic and Microbiologic Criteria for Diagnosis NTM Pulmonary Diseasea
Clinical | Pulmonary or Systemic Symptoms | Both clinical and radiologic criteria required |
Radiologic | Nodular or cavitary opacities on chest radiograph, or a high-resolution computed tomography scan that shows bronchiectasis with multiple small nodules | |
and | Appropriate exclusion of other diagnoses | |
Microbiologicb |
|
When 2 positive cultures are obtained, the isolates should be the same bNTM species (or subspecies in the case of M. abscessus) in order to meet disease criteria.
Treatment
Treatment
Treatment of NTM Pulmonary Disease
Mycobacterium avium Complex (MAC) (Table 2)
Mycobacterium kansasii (Table 2)
Mycobacterium xenopi (Table 2)
Mycobacterium abscessus
Surgical Resection
Table 2. Recommended Treatment Regimens for Mycobacterium avium complex, M. kansasii, and M. xenopi Pulmonary Disease
Organism | No. of Drugs | Preferred Drug Regimena | Dosing Frequency |
---|---|---|---|
M. aviums | |||
Nodular-bronchiectatic | 3 | Azithromycin (clarithromycin) Rifampicin (rifabutin) Ethambutol | 3 times weekly |
Cavitary | ≥3 | Azithromycin (clarithromycin) Rifampicin (rifabutin) Ethambutol Amikacin IVb (streptomycin) | Daily (3 times weekly may be used with IV aminoglycosides) |
Refractoryc | ≥4 | Azithromycin (clarithromycin) Rifampicin (rifabutin) Ethambutol Amikacin liposome inhalation suspension or Amikacin IVb (streptomycin) | Daily (3 times weekly may be used with IV aminoglycosides) |
M. kansasii | |||
3 | Azithromycin (clarithromycin) Rifampicin (rifabutin) Ethambutol | Daily | |
3 | Azithromycin (clarithromycin) Rifampicin (rifabutin) Ethambutol | 3 times weekly | |
3 | Isoniazid Rifampicin (rifabutin) Ethambutol | Daily | |
M. xenopi | |||
≥3 | Azithromycin (clarithromycin) and/or moxifloxacin Rifampicin (rifabutin) Ethambutol Amikacinb | Daily (3 times weekly may be used with IV aminoglycosides) |
b Consider for cavitary, extensive nodular/bronchiectatic disease or macrolide-resistant MAC. Amikacin or streptomycin may be given 3 times a week.
c Refractory disease is defined as remaining sputum culture positive after 6 months of guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been shown to improve culture conversion when added to guideline-based therapy in treatment refractory patients with MAC pulmonary disease.
Table 3. Dosing Guidelines for Drugs Used in the Management of NTM Pulmonary Disease
Drug | Daily Dosing | Thrice Weekly Dosing | Hepatic Impairment | Renal Impairment |
---|---|---|---|---|
Oral | ||||
Azithromycin | 250–500 mg per day | 500 mg per day | N/A | N/A |
Ciprofloxacin | 500–750 mg twice per day | N/A | N/A | 250–500 mg dosed at intervals according to CrCl |
Clarithromycin | 500 mg twice per day | 500 mg twice per day | N/A | Reduce dose by 50% if CrCl <30 mL/min |
Clofaziminea | 100–200 mg per day | N/A | Caution in severe hepatic impairment | N/A |
Doxycycline | 100 mg once to twice a day | N/A | N/A | N/A |
Ethambutol | 15 mg/kg per day | 25 mg/kg per day | N/A | Increase dosing interval (eg, 15–25 mg/kg, 3 times per week) |
Isoniazid | 5 mg/kg up to 300 mg per day | N/A | Caution | N/A |
Linezolid | 600 mg once or twice per dayb | N/A | N/A | N/A |
Moxifloxacin | 400 mg per day | N/A | N/A | N/A |
Rifabutin | 150–300 mg per day (150 mg per day with clarithromycin) | 300 mg per day | Caution | Reduce dose by 50% if CrCl <30 mL/min |
Rifampicin (rifampin) | 10 mg/kg (450 mg or 600 mg) per day | 600 mg per day | Caution | N/A |
Trimethoprim/ sulfamethoxazole | 800 mg/160 mg tab twice daily | N/A | Caution | Reduce dose by 50% if CrCl 5–30 mL/min |
Parenteral | ||||
Amikacin (IV) | 10–15 mg/kg per dayc, adjusted according to drug level monitoringd | 15–25 mg/kg per dayc, adjusted according to drug level monitoringd | N/A | Reduce dose or increase dosing interval (eg, 15 mg/kg, 2–3 times per week) |
Cefoxitin (IV) | 2–4 g 2–3 times daily (maximum daily dose is 12 g/day) | N/A | N/A | Reduce dose or increase dosing interval |
Imipenem (IV) | 500–1000 mg, 2–3 times per day | N/A | N/A | Reduce dose or increase dosing interval |
Streptomycin (IV or IM) | 10–15 mg/kg per day, adjusted according to drug level monitoring | 15–25 mg/kg per day, adjusted according to drug level monitoring | N/A | Reduce dose or increase dosing interval (eg, 15 mg/kg, 2–3 times per week) |
Tigecycline (IV) | 25–50 mg once or twice per dayb | N/A | 25 mg once or twice daily per day in severe hepatic impairment | N/A |
Inhalation | ||||
Amikacin liposome inhalation suspension | 590 mg per day | N/A | N/A | N/A |
Amikacin, parenteral formulation | 250–500 mg per day | N/A | N/A | N/A |
b Most experts recommend once daily dosing of linezolid and tigecycline due to the high rate of drug-related adverse reactions associated with twice daily dosing.
c The use of the described regimens for 15 weeks was associated with permanent ototoxicity in approximately one third of patients, and the risk was associated with age and cumulative dose. Given the high rates of ototoxicity, risks and benefits should be carefully considered in light of the goals of therapy. Clinicians should consider lower dose ranges and probably rely on intermittent dosing when more prolonged therapy is employed.
d Drug level monitoring: Trough <5 mg/L; Peak with daily dosing 35–45 μg/mL; Peak with intermittent dosing 65–80 μg/mL.
Table 4. Common Adverse Drug Reactions and Monitoring Recommendationsa
Drug | Adverse Reactions | Monitoring |
---|---|---|
Azithromycin/ clarithromycin | Gastrointestinal | Clinical monitoring |
Tinnitus/hearing loss | Audiogram | |
Hepatotoxicity | Liver function tests | |
Prolonged QTc | ECG (QTc) | |
Clofazimine | Tanning of skin and dryness | Clinical monitoring |
Hepatotoxicity | Liver function tests | |
Prolonged QTc | ECG (QTc) | |
Doxycycline | GI upset | Clinical monitoring |
Photosensitivity | Clinical monitoring | |
Tinnitus/vertigo | Clinical monitoring | |
Ethambutol | Ocular toxicity | Visual acuity and color discrimination |
Neuropathy | Clinical monitoring | |
Isoniazid | Hepatitis | Liver function tests |
Peripheral neuropathy | Clinical monitoring | |
Linezolid | Peripheral neuropathy | Clinical monitoring |
Optic neuritis | Visual acuity and color discrimination | |
Cytopenias | Complete blood count | |
Moxifloxacin | Prolonged QTc | ECG (QTc) |
Hepatotoxicity | Liver function tests | |
Tendinopathy | Clinical monitoring | |
Trimethoprim/ sulfamethoxazole | GI upset | Clinical monitoring |
Cytopenias | Complete blood count | |
Hypersensitivity | Clinical monitoring | |
Photosensitivity | Clinical monitoring | |
Rifabutin | Uveitis | Visual acuity |
Rifabutin/ Rifampicin (rifampin) | Hepatotoxicity | Liver function test |
Cytopenias | Complete blood count | |
Hypersensitivity | Clinical monitoring | |
Orange discoloration of secretions | ||
Amikacin, streptomycin, tobramycin | Vestibular toxicity | Clinical monitoring |
Ototoxicity | Audiograms | |
Nephrotoxicity | BUN, creatinine | |
Electrolyte disturbances | Calcium, magnesium, potassium | |
Amikacin liposome inhalation suspension | Dysphonia | Clinical monitoring |
Vestibular toxicity | Clinical monitoring | |
Ototoxicity | Audiograms | |
Nephrotoxicity | BUN, creatinine | |
Cough | Clinical monitoring | |
Dyspnea | Clinical monitoring | |
Cefoxitin | Cytopenias | Complete blood count |
Hypersensitivity | Clinical monitoring | |
Imipenem | Rashes | Clinical monitoring |
Cytopenias | Complete blood count | |
Nephrotoxicity | BUN/Creatinine | |
Tigecycline | Nausea/vomiting | Clinical monitoring |
Hepatitis/pancreatitis | Liver function tests, amylase/lipase |
Monitoring frequency should be individualized based on treatment regimen, age, comorbidities, concurrent drugs, overlapping drug toxicities, and resources.
Recommendation Grading
Abbreviations
- AFB: Acid-fast Bacilli
- BUN: Blood Urea Nitrogen
- CrCl: Creatinine Clearance
- ECG: Electrocardiogram
- GI: Gastrointestinal
- IM: Intramuscular
- IV: Intravenous
- N/A: Not Applicable
- NTM: Nontuberculous Mycobacteria
- QTc: Corrected QT
Source Citation
Charles L Daley, Jonathan M Iaccarino, Jr, Christoph Lange, Emmanuelle Cambau, Richard J Wallace, Claire Andrejak, Erik C Böttger, Jan Brozek, David E Griffith, Lorenzo Guglielmetti, Gwen A Huitt, Shandra L Knight, Philip Leitman, Theodore K Marras, Kenneth N Olivier, Miguel Santin, Jason E Stout, Enrico Tortoli, Jakko van Ingen, Dirk Wagner, Kevin L Winthrop, Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline: Executive Summary, Clinical Infectious Diseases, , ciaa241, https://doi.org/10.1093/cid/ciaa241