CONTENTS
- Basics
- Epidemiology
- Clinical manifestations
- Diagnosis
- Treatment
- Treatment overview
- Antibiotic regimens for various species:
- Slow-growing:
- Rapidly-growing
- Questions & discussion
abbreviations used in the pulmonary section: 3
- ABPA: Allergic bronchopulmonary aspergillosis 📖
- AE-ILD: Acute exacerbation of ILD 📖
- AEP: Acute eosinophilic pneumonia 📖
- AFB: Acid Fast Bacilli
- AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
- ANA: Antinuclear antibody 📖
- ANCA: Antineutrophil cytoplasmic antibodies 📖
- ARDS: Acute respiratory distress syndrome 📖
- ASS: Antisynthetase Syndrome 📖
- BAL: Bronchoalveolar lavage 📖
- BiPAP: Bilevel positive airway pressure 📖
- CEP: Chronic eosinophilic pneumonia 📖
- CF: Cystic fibrosis 📖
- COP: Cryptogenic organizing pneumonia 📖
- CPAP: Continuous positive airway pressure 📖
- CPFE: Combined pulmonary fibrosis and emphysema 📖
- CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
- CTEPH: Chronic thromboembolic pulmonary hypertension 📖
- DAD: Diffuse alveolar damage 📖
- DAH: Diffuse alveolar hemorrhage 📖
- DIP: Desquamative interstitial pneumonia 📖
- DLCO: Diffusing capacity for carbon monoxide 📖
- DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
- EGPA: Eosinophilic granulomatosis with polyangiitis 📖
- FEV1: Forced expiratory volume in 1 second 📖
- FVC: Forced vital capacity 📖
- GGO: Ground glass opacity 📖
- GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
- HFNC: High flow nasal cannula 📖
- HP: Hypersensitivity pneumonitis 📖
- IPAF: Interstitial pneumonia with autoimmune features 📖
- IPF: Idiopathic pulmonary fibrosis 📖
- IVIG: Intravenous immunoglobulin 📖
- LAM: Lymphangioleiomyomatosis 📖
- LIP: Lymphocytic interstitial pneumonia 📖
- MAC: Mycobacterium Avium complex 📖
- MCTD: Mixed connective tissue disease 📖
- NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
- NSIP: Nonspecific interstitial pneumonia 📖
- NTM: Non-tuberculous mycobacteria 📖
- OP: Organizing pneumonia 📖
- PAP: Pulmonary alveolar proteinosis 📖
- PE: Pulmonary embolism 📖
- PFT: Pulmonary function test 📖
- PLCH: Pulmonary Langerhans Cell Histiocytosis 📖
- PPFE: Pleuroparenchymal fibroelastosis 📖
- PPF: Progressive pulmonary fibrosis 📖
- PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
- RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
- RP-ILD: Rapidly progressive interstitial lung disease 📖
- TNF: tumor necrosis factor
- UIP: Usual Interstitial Pneumonia 📖
- Nontuberculous mycobacteria (NTM) refers to hundreds of species of mycobacteria.
- NTM are often not very virulent organisms. In many clinical contexts, NTM may be more likely to be colonizing organisms than to be the cause of clinical disease. Thus, the diagnosis of NTM disease is challenging, requiring a synthesis of clinical symptomatology, radiologic data, and microbiologic data.
- Mycobacterium avium complex (MAC) refers to a dozen species, most notably M. avium, M. intracellulare, and M. chimaera. These species have similar clinical behavior and treatment, so the precise species isn't clinically important.
basics
- NTM species are commonly found in soil and municipal water systems, but they are usually harmless for most people.
- Acquisition of NTM commonly occurs following aerosolization of water (e.g., showering, hot tub exposure). (Murray 2022) Unlike M. tuberculosis, NTM don't exist in a latent state within patients.
- Due to falling rates of M. tuberculosis, NTM is the primary cause of mycobacterial infection in developed countries. (Fishman 2023)
risk factors for disease
- The epidemiology of different forms of NTM disease are often unique. These are discussed further below.
basics
- This mimics reactivation tuberculosis.
- Fibrocavitary disease is usually due to MAC (Mycobacterium avium complex) or M. kansasii, but may also be caused by M. xenopi or M. abscessus. (36213301)
epidemiology
- Often affects men who are middle-aged or elderly.
- Risk factors:
- Underlying structural lung disease (e.g., COPD, silicosis, bronchiectasis, interstitial lung disease).
- Alcoholism, smoking history.
- Chronic cardiovascular or liver disease.
- HIV is a risk factor for infection with M. kansasii. (Murray 2022)
clinical presentation
- Overall, this resembles postprimary tuberculosis.
- Chronic productive cough is the most common symptom, occasionally with hemoptysis.
- Constitutional symptoms are usually less prominent than in tuberculosis (fever is uncommon).
radiology of fibrocavitary NTM
basic features
- (1) Cavitation:
- Present in most patients (~90%), bilateral in ~20%.
- Scarring may cause volume loss.
- (2) Tree-in-bud opacities may be seen, due to endobronchial spread.
- Pleural thickening may be seen. (34627854)
features suggesting NTM, rather than M. tuberculosis
- (1) NTM infection more frequently involves the apical and anterior segments of upper lobes (whereas M. tuberculosis typically involves the apical and especially posterior segments of the upper lobes).
- (2) Compared to tuberculosis, there is a greater amount of cavitation relative to the total lung involvement (with little parenchymal infiltrate).
- (3) Cavities usually have a thinner wall than M. tuberculosis.
- (4) There is a lower frequency of pleural effusion (~10%, compared to 15% with M. tuberculosis).
- (5) There is more pleural thickening. (34627854)
- (6) Less bronchogenic spread, but more contiguous spread. (37890914)
- (Further discussion of the radiology of postprimary M. tuberculosis is here: 📖)
epidemiology
- Typically involves women >50 years old.
- Usually, there is no prior history of smoking or structural lung disease.
- Patients are often thin. They may have subtle thoracic abnormalities that impede secretion clearance (e.g., mild scoliosis, pectus excavatum).
- Causative organism:
- Usually due to Mycobacterium avium complex (MAC).
- Less often this is due to M. abscessus.
- Some reports describe causation by Mycobacterium kansasii.
clinical presentation
- Cough may be variably productive.
- Constitutional symptoms:
- Fatigue and malaise may occur, but aren't common.
- Fever usually doesn't occur.
- Clinical progression may occur over a very slow timeframe (years).
radiology
dominant features
- (1) Tree-in-bud nodules:
- The initial finding is generally tree-in-bud nodules.
- The lingula and right middle lobe are most often involved, but any lobe can be involved. (Shepard 2019)
- Nodules usually grow up to ~1.5 cm in size. (Shepard 2019)
- (2) Cylindrical bronchiectasis:
- Over time, bronchiectasis may develop.
- Bronchiectasis rarely progresses to the most severe (cystic) form.
other features
- Small nodules in distant areas of the lung may occur due to endobronchial spread. Sometimes, random nodules occur up to ~2 cm, which may occasionally cavitate. (Walker 2019)
- Mediastinal lymphadenopathy is occasionally seen.
- Mosaic attenuation can occur.
basics
- NTM may be found in the sputum of ~10% of cystic fibrosis patients.
- The most common isolates are MAC (Mycobacterium avium complex) and Mycobacterium abscessus.
- In many patients, NTM doesn't seem to be associated with adverse clinical events. Sorting out whether the NTM is causing disease may be very challenging.
- Annual screening for NTM using expectorated sputum is recommended by the 2016 Cystic Fibrosis Foundation guidelines. (37890921)
potential indications that NTM is pathogenic
- Clinical deterioration despite aggressive optimization of cystic fibrosis management (e.g., antibiotic therapy for conventional bacteria, management of allergic bronchopulmonary aspergillosis, treatment of sinus disease, aggressive airway clearance, etc.). (37890914)
- CT scan:
- Prominent tree-in-bud opacities may suggest infection.
- Cavitation is more worrisome for progressive disease.
- High bacterial load, for example:
- Acid-fast bacilli are visible on sputum smear.
- Consistent isolation of NTM in sputum on several occasions.
- More virulent species of NTM.
management
- Azithromycin monotherapy should be avoided, to avoid the induction of drug resistance. Chronic therapy with outpatient azithromycin may be beneficial for cystic fibrosis, but this must be avoided in patients with NTM infection or colonization.
- Airway clearance should be utilized as for other patients with cystic fibrosis (e.g., vest therapy, nebulized hypertonic saline, expiratory flutter valve).
- Anti-NTM antimicrobials are generally similar to those for other patients, but there are some differences:
- Daily therapy may be preferable to thrice weekly therapy, given concerns regarding drug absorption and lung penetration.
- Rifamycins interact with ivacaftor and tezacaftor, so these may need to be avoided.
- Higher doses of some antibiotics may be needed, due to altered pharmacokinetics in patients with cystic fibrosis. (37890921)
- Surgical therapy for NTM infection: Given impaired pulmonary function, resection surgery for therapy of NTM infection should be considered only under extraordinary circumstances. (37890921)
- Transplantation:
- Some NTM infections may be considered a contraindication to transplantation (especially M. abscessus), although successful transplantation outcomes have been reported.
- If treatment of NTM infection is successful with culture conversion, this may improve candidacy for lung transplantation. (37890921)
- Relationship between NTM and bronchiectasis?
- NTM infection is usually a result of bronchiectasis, rather than the cause of bronchiectasis. (30586519)
- However, there are definitely situations where NTM may cause bronchiectasis, for example:
- Lady Windermere syndrome (discussed above: 📖).
- Mycobacterium kansasii may have a tendency to cause more invasive disease, with resulting bronchiectasis.
- NTM often complicates bronchiectasis that is due to a prior infection from tuberculosis or Mycobacterium kansasii. In the context of prior M. tuberculosis infection, the differential diagnosis may be NTM superinfection vs. relapse of prior M. tuberculosis infection.
epidemiology
- Disseminated MAC is usually seen in severe AIDS (with CD4 count <50-70/uL). (ERS handbook 3rd ed.)
- Disseminated MAC may rarely also be seen in other contexts:
- Leukemia/lymphoma.
- Transplantation.
- Cytokine dysfunction (interferon gamma, tumor necrosis factor, or IL-12).
- As an intravascular infection involving catheters or prosthetic devices. (Murray 2022)
clinical presentation
- Constitutional symptoms (fever, weight loss, night sweats).
- Diarrhea, anorexia, and abdominal pain. Abdominal CT scan may show hepatomegaly, splenomegaly, and/or lymphadenopathy.
- Adrenal insufficiency may occur.
- Pulmonary disease occurs in only 5% of patients (although pneumonia and thoracic lymphadenopathy may be seen). (Murray 2022)
thoracic radiology
- Chest X-ray is typically normal.
- CT scan may show:
- Endobronchial lesions (appearing as submucosal “pearls”).
- Lymphadenopathy, which may display peripheral enhancement and central low-density central necrosis 📖 (similar to M. tuberculosis). (Murray 2022)
- Nodules, including a miliary pattern.
- Focal consolidation with cavitation. (Shepard 2019)
laboratory studies & specific diagnosis
- Anemia and elevated alkaline phosphatase level may be seen.
- MAC may be detected via blood culture with surprisingly high sensitivity (~90%). Multiple cultures should be obtained, ideally using a mycobacterial blood culture medium (this needs to be ordered specifically as “blood AFB culture”). Cultures turn positive on average in two weeks.
- Culture may also be obtained from bone marrow, liver biopsy, or lymph node biopsy. (Murray 2022)
management
- Treatment has many similarities to pulmonary MAC infection. Management is generally directed by an infectious disease specialist, given the relatively minimal pulmonary involvement from these infections and the frequent coinfection with HIV.
- Steroid replacement may occasionally be required for management of adrenal insufficiency.
epidemiology
- Hypersensitivity may be caused by exposure to NTM, especially via hot tubs that may be growing MAC (Mycobacterium avium complex).
- Patients are typically young and without prior lung disease.
clinical presentation
- Severity varies from mild symptoms to respiratory failure requiring intubation.
- CT scan may show features of acute hypersensitivity pneumonitis (e.g., centrilobular nodules and ground-glass opacities). More on the radiology of acute hypersensitivity pneumonitis: 📖
- MAC may be isolated from lung specimens.
management
- As with hypersensitivity pneumonitis, the most important therapy is avoidance of any additional exposure.
- Steroid may hasten recovery in severe cases, but overall its use in hypersensitivity pneumonia is unclear. (More on the treatment of hypersensitivity pneumonia: 📖)
The question is always: invasive disease vs. colonization vs. contamination. NTM are frequently present in the environment, so environmental contamination may be more likely, as compared to other types of bacteria.
interpretation of a single positive culture
- A single sputum culture (especially with a small number of organisms) is generally insufficient to diagnose NTM infection.
- A positive AFB smear implies a greater bacterial load than merely a positive culture, so this may be more suggestive of active disease. (ERS handbook 3rd ed.)
- The species identity may help (discussed further below).
multiple cultures are generally needed
- Ideally three or more sputum specimens should be sent for AFB culture and smear, obtained early in the morning on different days over at least a week. (34627854, 2020 guidelines)
- Isolation of AFB from at least two separate samples is often regarded as a “positive” result.
bronchoscopy versus sputum culture
- Overall, culture yield from bronchoscopy seems to be equivalent to culture yield from sputum. (11402614, 2020 guidelines) However, it is conceivable that bronchoscopy is overly sensitive (thereby tending to detect NTM in situations where they are not truly pathogenic). (37890914)
- Role of bronchoscopy?
- (a) Bronchoscopy should be utilized only among patients who are both unable to produce sputum and also unable to undergo induced sputum.
- (b) Exclusion of alternative diagnoses is probably the greatest benefit of bronchoscopy. In most cases bronchoscopy is unnecessary, but it may be helpful in complex cases that involve several competing diagnoses.
- Diagnostic criteria (shown below) require the presence of two positive sputum cultures, or a single positive culture from bronchoscopy. This criterion doesn't reflect that bronchoscopy is superior to sputum culture, but rather that patients ideally shouldn't be subjected to repeat bronchoscopy. (Murray 2022)
- If bronchoscopy is performed, care should be taken to avoid any contamination with tap water (which may contain mycobacteria). Pseudo-outbreaks have occurred due to bronchoscope contamination with M. abscessus, M. simiae, and M. immunogenum. (Murray 2022)
relative pathogenicity of various species
less likely to be pathogenic
- Species that are generally nonpathogenic and usually represent contaminants: (37890914)
- M. gordonae is relatively nonpathogenic and almost invariably represents contamination.
- M. terrae complex.
- M. mucogenicum.
- Species known to be in tap water that may cause infection, but may reflect contamination: (37890914)
- M. simiae.
- M. lentiflavum.
- Other species that are less likely to be pathogenic: (35236564)
- M. fortuitum.
- M. chelonae.
more likely to be pathogenic
- M. kansasii isn't generally a contaminant or a colonizer, so it should almost always be considered to be a pathogen. (Murray 2022) Unlike other NTM, M. kansasii isn't frequently found in nature (although it may be found in the tap water of some cities). M. kansasii is perhaps the most virulent NTM species. (Murray 2022)
caveats about these diagnostic criteria:
- ⚠️ Diagnostic criteria in general are never intended for rigid application, but rather as a general guide.
- ⚠️ Diagnostic criteria have not been prospectively validated. (Absence of a gold-standard to define infection renders validation impossible. The ideal way to rigorously validate the criteria would be to apply them to hundreds of patients prospectively, withhold therapy from all patients, and determine which patients deteriorated over the next decade – which is clearly unethical and logistically impossible).
- ⚠️ Criteria were based on data from more common, pathogenic species of NTM. It's dubious where these criteria are applicable to all species of NTM. (37890914)
- ⚠️ Meeting diagnostic criteria does not indicate that treatment is necessarily indicated.
- ⚠️ If the diagnosis is unclear, patients should undergo ongoing longitudinal follow-up to ensure that clinically relevant disease isn't being missed. NTM is generally a chronic disease process, so there is usually sufficient time to clarify the diagnosis.
ATS/ERS/IDSA criteria for NTM infection
- (1) Symptoms (pulmonary and/or systemic).
- (2) Radiology: at least one of the following:
- Nodular or cavitary opacities on chest radiograph.
- CT scan showing bronchiectasis with multiple small nodules.
- (3) Microbiology: at least one of the following:
- Positive culture from at least two separate expectorated sputum samples:
- Two cultures must yield the same organism.
- Ideally, cultures should be separated by >1 week (to prove persistence over time).
- Positive culture result from at least one bronchial wash or lavage.
- Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or acid-fast bacilli) plus positive culture for NTM. The positive culture may be from the biopsy, sputum, or bronchial washings.
- Positive culture from at least two separate expectorated sputum samples:
- (4) Exclusion of other diagnoses. (2020 guidelines)
Meeting the above criteria doesn't necessarily indicate that treatment is beneficial. Below are important factors to consider in determining whether to pursue treatment.
specific NTM species
- How virulent is the species? (discussed above 📖)
- How likely is the species to respond to therapy?
prognostic features predicting disease progression favor treatment:
- Cavitary lung disease should generally be treated. (35236564)
- Degree of culture positivity:
- Individual patient's disease course:
- Progressive deterioration over time favors treatment (whereas stability doesn't).
- Sustained inability to spontaneously clear cultures over time supports a decision to treat (whereas some patients will spontaneously clear NTM on their own).
- Low body mass index, low albumin (<3.5 g/dL). (36213301)
- Alternatively: advanced age or comorbidities that limit life expectancy would argue against treatment (because the patient may be unlikely to live long enough to experience disease progression). (Murray 2022)
patient-centered considerations
- Severity of symptoms.
- Ability to tolerate therapy.
- Patient's preferences and dedication to therapy (adhering to treatment is often difficult).
airway clearance and bronchiectasis therapy
- Airway clearance therapy is a fundamental therapy, even for patients who are not undergoing antibiotic therapy. Various techniques may include: (Fishman 2023)
- Hypertonic saline nebulized therapy.
- Expiratory flutter valve devices
- High-frequency chest wall oscillation vests.
- Aerobic exercise. (36213301)
antibiotic therapy
- Complex multidrug antibiotic regimens are required.
- Regimens for the more common NTM species are explored further below:
surgery
- Indications to consider surgery:
- Failure of response to medical therapy.
- Focal disease.
- Sufficient lung tissue to tolerate resection.
- Refractory hemoptysis (despite interventional radiology embolization of bronchial arteries).
- Patients are at risk for a variety of complications. If necessary, surgery should ideally be performed at a large-volume center with experience in performing resective surgery for NTM. (Murray 2022)
basics
- Susceptibility-based treatment for macrolides (23S rRNA gene) and amikacin (16S rRNA) is recommended over empiric therapy. (2020 guidelines) Culture conversion after six months is markedly lower if there is resistance to clarithromycin (25% vs. 84%). (34627854) Other resistance assays may not correlate with clinical outcomes, so they are less relevant. (Murray 2022)
- Patients should generally receive a minimum of three drugs (e.g., azithromycin, ethambutol, rifampin). If a macrolide is utilized, the addition of two additional medications (e.g., rifamycin plus ethambutol; or clofazimine plus ethambutol) has been shown to prevent the emergence of macrolide resistance during therapy. (2020 guidelines)
various treatment regimens
(1) macrolide
- A macrolide should be utilized for any patient with macrolide sensitivity.
- Azithromycin is preferred over clarithromycin given better tolerance, fewer drug-drug interactions (especially with rifampin), lower pill burden, single daily dosing, and equal efficacy. However, occasional patients may be unable to tolerate azithromycin, yet able to tolerate erythromycin. (2020 guidelines)
- Dose:
- Nodular/bronchiectatic disease: Azithromycin 500 mg three times/week (preferred over clarithromycin 1,000 mg).
- Cavitary disease, severe/advanced disease, or previously treated: Azithromycin 250 mg daily (preferred over clarithromycin 500-1,000 mg).
(2) ethambutol
- Ethambutol may be the most important agent to prevent the development of macrolide resistance.
- Dose:
- Nodular/bronchiectatic disease: Ethambutol 25 mg/kg three times/week.
- Cavitary disease, advanced disease, or previously treated: Ethambutol 15 mg/kg daily.
(3) rifampin
- Rifabutin may be useful in some cases instead of rifampin, to avoid drug-drug interactions. (31685155)
- Dose:
- Nodular/bronchiectatic disease: Rifampin 600 mg three times/week.
- Cavitary disease, advanced disease, or previously treated:
- Rifampin 450-600 mg daily (target ~10 mg/kg; 450 if <50 kg weight).
- Rifabutin 150-300 mg daily.
(4) intravenous amikacin
- Indications:
- (1) Cavitary disease, advanced or previously treated: augment with four-drug therapy for the first 2-3 months.
- (2) Macrolide resistant MAC: aminoglycoside may be needed for six or more months.
- Dose: 15 mg/kg IV/IM, three times per week.
(5) amikacin liposomal inhalation suspension (ALIS)
- This may be added for treatment-resistant disease (failure to clear sputum after 6 months). The CONVERT trial demonstrated that addition of ALIS increased culture conversion from 10% to 30% among patients who failed to convert after six months. (30216086) Unfortunately, respiratory side effects are common (including cough, dysphonia, dyspnea, and hemoptysis) and nephrotoxicity or ototoxicity can occur. (35236564)
- Note that the breakpoint for amikacin liposomal inhalation suspension (≧ 128 ug/mL) is higher than the breakpoint for parenteral amikacin (≧ 64 ug/mL). Therefore, some patients who are deemed “resistant” to intravenous amikacin could remain sensitive to inhaled amikacin. (2020 guidelines)
- Dose: inhaled suspension 590 mg once daily. If ALIS isn't available, the use of inhaled parenteral amikacin is a reasonable alternative. (2020 guidelines)
response to treatment & duration of therapy
- Ideally cultures will clear by ~6 months. Inhaled liposomal amikacin may be beneficial if cultures don't clear by six months (as discussed above). (30216086)
- Treatment should continue until patients have consistent negative sputum cultures for 12 months. (2020 guidelines) Generally this requires a minimum of ~18-24 months total therapy.
general
- M.kansasii is the most virulent species of NTM, with many parallels to M. tuberculosis. Unlike most NTM, M. kansasii isolation usually reflects invasive infection (more on this above 📖).
- Patients should be screened for HIV, given its association with M. kansasii. Among patients with HIV, M. kansasii is usually associated with CD4 <100/uL and may cause nearly any radiographic abnormality. (Murray 2022)
- M. kansasii is usually susceptible to a wide array of agents (e.g., macrolides, rifamycins, fluoroquinolones, ethambutol, isoniazid, trimethoprim-sulfamethoxazole, and aminoglycosides). (Murray 2022) However, there is intrinsic resistance against pyrazinamide.
- M. kansasii is the most treatable species of NTM. Almost all appropriately treated patients will achieve sputum clearance. Subsequently, there is a low relapse rate (~5%). (Fishman 2023, 2020 guidelines)
- Rifampicin and clarithromycin are the key drugs to test for sensitivity. (2020 guidelines)
typical regimen
- (1) Rifampin (600 mg/day):
- Testing for rifamycin resistance is recommended (rpo β gene). (2020 guidelines)
- For patients who are sensitive to rifamycins, a rifamycin-based treatment regimen is usually very effective. (2020 guidelines)
- If resistant to rifamycins, moxifloxacin may be used instead. (Fishman 2023)
- (2) Ethambutol (15 mg/kg daily for 18 months).
- (3) Isoniazid (300 mg/day) or a macrolide.
- Rifampin-ethambutol-isoniazid has demonstrated excellent outcomes and is widely used. (2020 guidelines)
duration of therapy
- Sputum clearance is usually achieved by 4 months; if this fails to occur then expert consultation should be sought. (Fishman 2023, 2020 guidelines)
- Therapy can generally be stopped after one year. (2020 guidelines)
basics
- M. xenopi is a thermophilic bacteria that survives in hot water systems. Its ability to withstand common disinfectants may lead to contamination of medical devices (e.g., bronchoscopes), leading to false-positive culture results (“pseudo-epidemics”).
- Radiographic findings vary, but may include upper lobe cavitation suggestive of tuberculosis. (Murray 2022) M. xenopi is associated with chronic pulmonary aspergillosis.
- Clinical infection with M. xenopi is associated with a high mortality (5-year mortality of ~50%). (2020 guidelines) However, it's unclear to what extent the M. xenopi infection itself causes this mortality (versus the infection being a marker of an unwell host).
treatment basics
- Overall treatment efficacy is limited (with sustained clearance in perhaps only a third of patients). (Murray 2022)
- Efficacy of susceptibility-based treatment is unclear. (2020 guidelines)
- Treatment should be continued at least one year after sputum clearance.
usual regimen
- Rifampin 450-600 mg (10 mg/kg) PO daily.
- Ethambutol 15 mg/kg PO daily.
- Azithromycin 250-500 mg PO daily (or moxifloxacin 400 mg PO daily).
- Plus amikacin 15-25 mg/kg IV three times weekly – if cavitary or extensive disease.
basics
- M. abscessus complex is the second most common NTM group causing human disease (after MAC). This group includes three subspecies (M. abscessus, M. bolletii, M. massiliense). (Fishman 2023)
epidemiology
- M. abscessus mostly affects older women, causing nodular bronchiectasis (similar to Mycobacterium avium complex).
- Patients with cystic fibrosis may experience a more aggressive disease course.
treatment basics
- Infection may be incurable, even with complex medication regimens.
- Susceptibility-based treatment is recommended for treatment with macrolides and amikacin. (2020 guidelines)
- The most important resistance mechanism is an inducible erm gene named erm(41), which confers resistance to macrolides. Since resistance is inducible, it won't be identified by in vitro antibiotic susceptibilities unless testing is performed after incubation with macrolides for two weeks. Genetic testing for the erm(41) gene alone is insufficient, since this may incorrectly classify the isolate as susceptible. (35236564)
- Mycobacterium abscessus subspecies bolletii and subspecies abscessus often have an inducible erm gene. (37133589)
- Mycobacterium abscessus subspecies massiliense has a nonfunctional erm(41) gene, so they may be susceptible to macrolides. (2020 guidelines)
- Amikacin resistance is caused by a specific mutation (A1408G) in the 16S rRNA (rrs) gene.
- The most important resistance mechanism is an inducible erm gene named erm(41), which confers resistance to macrolides. Since resistance is inducible, it won't be identified by in vitro antibiotic susceptibilities unless testing is performed after incubation with macrolides for two weeks. Genetic testing for the erm(41) gene alone is insufficient, since this may incorrectly classify the isolate as susceptible. (35236564)
regimen
- Antibiotic selection is very complex. Treatment often involves 2-4 months of induction therapy with at least three medications (guided by susceptibility testing), followed by oral agents to which the isolate is susceptible.
- A macrolide should be utilized in the absence of macrolide resistance.
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Books:
- Shah, P. L., Herth, F. J., Lee, G., & Criner, G. J. (2018). Essentials of Clinical pulmonology. In CRC Press eBooks. https://doi.org/10.1201/9781315113807
- Shepard, JO. (2019). Thoracic Imaging The Requisites (Requisites in Radiology) (3rd ed.). Elsevier.
- Walker C & Chung JH (2019). Muller’s Imaging of the Chest: Expert Radiology Series. Elsevier.
- Palange, P., & Rohde, G. (2019). ERS Handbook of Respiratory Medicine. European Respiratory Society.
- Rosado-De-Christenson, M. L., Facr, M. L. R. M., & Martínez-Jiménez, S. (2021). Diagnostic imaging: chest. Elsevier.
- Murray & Nadel: Broaddus, V. C., Ernst, J. D., MD, King, T. E., Jr, Lazarus, S. C., Sarmiento, K. F., Schnapp, L. M., Stapleton, R. D., & Gotway, M. B. (2021). Murray & Nadel’s Textbook of Respiratory Medicine, 2-Volume set. Elsevier.
- Fishman's: Grippi, M., Antin-Ozerkis, D. E., Cruz, C. D. S., Kotloff, R., Kotton, C. N., & Pack, A. (2023). Fishman’s Pulmonary Diseases and Disorders, Sixth Edition (6th ed.). McGraw Hill / Medical.
- Teneback CC and Garcia B. Bronchiectasis. Humana Press, 2022.