Background
- Mycobacteria that excludes tuberculosis and leprosy
Microbiology
- Acid-fast bacilli, free-living in the environment
- Direct microscopy with auremine rodhamine fluorochrome stain (better than Ziehl-Neelsen)
- Broadly divided into slow-growers and fast-growers
- Fast-growers produce colonies within 7 days on solid media
- Grows optimally at 28-30º C, with some preferring 35 ºC
- May grow in blood culture if mycobacteremic
- Slow-growers produce colonies after more than 7 days on solid media
- MAC, Mycobacterium xenopi, and Mycobacterium kansasii are the three most important
- Grows optimally at 35-37º C except Mycobacterium haemophilum (28-30 ºC) and Mycobacterium xenopi (42-45 ºC)
- Fast-growers produce colonies within 7 days on solid media
- Media includes blood or chocolate agar, MTBC media, etc
- Species-level identification requires molecular tests
Species
- More than 200 species of Mycobacterium spp. that are not in Mycobacterium tuberculosis complex or Mycobacterium leprae
- Often divided into rapid growers (visible in culture in less than 5-7 days) and slow growers (more than 7 days)
- Slow-growers are further classified by production of yellow-orange pigment
- Photochromagens produce pigment when exposed to light
- Scotochromogens produce pigment regardless of light
- Nonchromogens do not produce pigment
Pathophysiology
- Inhalation ± microaspiration, likely from water source
- Environmental organisms that are essentially unavoidable
- Response is cell-mediated with pulmonary macrophages, with assistance from CD4, IL-2, and IFN-γ
Epidemiology
- NTMs are distributed worldwide, present in soil, household water, vegetable matter, animals, and birds
- Also tap water (especially Mycobacterium gordonae, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium simiae, MAC, and Mycobacterium mucogenicum)
- 90% of patients with NTM infections have underlying pulmonary disease
- No person-to-person transmission
- In Ontario: Mycobacterium avium complex (25%), Mycobacterium xenopi (10%), Mycobacterium abscessus/Mycobacterium chelonae, Mycobacterium fortuitum
| Species | Distribution |
|---|---|
| Pulmonary Disease | |
| Mycobacterium abscessus | Worldwide; may be found concomitant with MAC |
| Mycobacterium avium complex | Worldwide; most common NTM pathogen in US |
| Mycobacterium kansasii | US, Europe, South Africa, and coal-mining regions |
| Mycobacterium malmoense | UK, northern Europe; uncommon in US |
| Mycobacterium xenopi | Europe, Canada; uncommon in US; associated with pseudoinfection |
| Lymphadenitis | |
| Mycobacterium avium complex | Worldwide; most common NTM pathogen in US |
| Mycobacterium malmoense | UK, northern Europe (especially Scandinavia) |
| Mycobacterium scrofulaceum | Worldwide; previously common, now rarely isolated in US |
| Disseminated Disease | |
| Mycobacterium avium complex | Worldwide; AIDS; most common NTM pathogen in US |
| Mycobacterium chelonae | US; non-AIDS immunosuppressed skin lesions |
| Mycobacterium haemophilum | AIDS; US, Australia; non-AIDS immunosuppressed |
| Mycobacterium kansasii | AIDS; US, South Africa |
| SSTI and MSK | |
| Mycobacterium abscessus | Penetrating injury |
| Mycobacterium chelonae | US, associated with keratitis and disseminated disease |
| Mycobacterium fortuitum | Penetrating injury, footbaths |
| Mycobacterium marinum | Worldwide, fresh- and saltwater |
| Mycobacterium ulcerans | Australia, tropics, Africa, Southeast Asia, not US |
| Contaminant | |
| Mycobacterium gordonae | Most common NTM contaminant |
| Mycobacterium haemophilum | |
| Mycobacterium mucogenicum | |
| Mycobacterium nonchromogenicum | |
| Mycobacterium terrae complex | |
Clinical Manifestations
| Syndrome | Species | Description |
|---|---|---|
| Pulmonary disease | MAC, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium abscessus | |
| Upper lobe cavitary | MAC, Mycobacterium kansasii | Male smokers, often alcohol use, usually early 50s |
| RML/lingular nodular bronchiectasis | MAC, Mycobacterium abscessus, Mycobacterium abscessus subsp. massiliense | Female nonsmokers, usually older than 60 |
| Localized alveolar/cavitary | Mycobacterium abscessus, MAC | Prior granulomatous disease (usually TB) with bronchiectasis |
| Reticulonodular or alveolar bilateral lower lobe | Mycobacterium fortuitum | Achalasia, chronic vomiting, exogenous lipoid pneumonia |
| Reticulonodular | MAC, Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense | Adolescents with CF, HIV-positive patients, prior bronchiectasis |
| Hypersensitivity pneumonitis | Mycobacterium immunogenum, Mycobacterium avium | Metal workers, indoor hot tubs |
| Cervical lymphadenitis | MAC | |
| SSTI | Mycobacterium fortuitum, Mycobacterium marinum, Mycobacterium chelonae, Mycobacterium ulcerans | |
| MSK | Mycobacterium marinum, MAC, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium abscessus, Mycobacterium chelonae | |
| Disseminated | HIV-positive: Mycobacterium avium and Mycobacterium kansasii;
HIV-negative: Mycobacterium abscessus and Mycobacterium chelonae |
|
| Catheter-related | Mycobacterium fortuitum, Mycobacterium abscessus, Mycobacterium chelonae |
Pulmonary Disease
- Risk factors include COPD and CF1
- Most common clinical manifestation of NTM
- Most commonly caused by MAC, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium abscessus
- Nonspecific chronic or subacute respiratory syndrome with prominent cough
Fibrocavitary Disease
- Usually preexisting lung disease (COPD etc), men
- Upper-lobe predominant, focal, cavitary
- DDx includes TB and lung cancer
Nodular Bronchiectatic Disease
- "Lady Windermere syndrome"
- RML/lingula with discrete nodules and bronchiectasis
- Usually no preexisting lung disease, non-smoker, women
Investigations
- Almost always needs CT; may repeat to monitor for progression
- 3 sputums for AFB; may treat Mycobacterium kansasii based on only a single colony but everything else needs 2-3 positives
- Rule out tuberculosis
Skin and Soft Tissue Infection
- From direct inoculation
- Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium marinum, Mycobacterium ulcerans
- Dx: tissue biopsy culture (best) or culture of discharge
Mycobacterium marinum
- "Fish tank granuloma"
- Incubation 2 to 3 weeks
- Small violet papular lesions on hands, which can ulcerate
- Can also cause sporotrichoid disease
Other Infections
Superficial Lymphadenitis
- Children, usually submandibular
- May be from eating dirt
Disseminated Disease
- Usually in AIDS or other significant cell-mediated immunosuppression
Mycobacterium chimaera Infection
- Outbreaks associated with heater units used in cardiac surgery
- Present with IE, sternal wound infections, mediastinitis, etc.
Diagnosis
- Sputum smear and culture for AFB
- Spontaneous, induced, or BAL
- PCR/NAAT can be done for TB and MAC, but only done on smear positive samples unless specifically requested
Diagnostic Criteria for Pulmonary Disease
- Diagnosis requires clinical, radiologic, and microbiologic criteria
- Clinical: pulmonary or systemic symptoms
- Radiologic: nodular or cavitary opacities on chest radiograph, or a high-resolution cCT scan that shows bronchiectasis with multiple small nodules
- Microbiologic:
- Positive cultures from at least 2 separate expectorate sputums, or
- One positive culture from bronchial wash or lavage
- Transbronchial or other lung biopsy with mycobacterial histologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM
- Exclusion of other diagnoses
Management
- Treatment decisions
- First is to decide whether or not to treat; must weigh the risks and benefits
- NTM can represent contamination, colonization, or infection/invasion
- The mycobacteria are inherently resistant to many bacteria, sometimes require IV therapy, multiple agents with toxicity, prolonged treatment
- Treatment often ineffective
- Recurrence is common; 50% of patients need a second course within 5 years of the first one
- Decide to start based on shared decision-making model, reviewing:
- Meets diagnostic criteria
- Comorbidities
- Toxicities
- Goals of care
- All rapid-growers are resistant to first-line TB treatment (RIPE), and have aspiration as an underlying risk factor
- Need susceptibilities for macrolides in MAC; needs to be specifically requested
Pulmonary Disease
Mycobacterium avium Complex
- MAC is the prototype
- Macrolide (azithromycin/clarithromycin) backbone, with 2 to 3 other agents depending on the disease type and severity
- Rifampin and clarithromycin interact, so prefer rifamycin
- Treat until 12 months after negative cultures
| Class | Nodular | Cavitary or Advanced |
|---|---|---|
| Macrolide | Clarithromycin 1000 tiw or azithromycin 500 tiw | Clarithromycin 500 bid or azithromycin 250 daily |
| Ethambutol | 25 mg/kg tiw | 15 mg/kg/day |
| Rifamycin | TMP 600 tiw | RMP 450-600 mg OD, or RFB 150-300 mg daily |
| Amikacin | — | Consider 10-15 mg/kg/day IV |
Mycobacterium kansasii
- Mycobacterium kansasii pulmonary disease: daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d)
- Patients should be treated until culture negative on therapy for 1 year
- Could consider treating based on a single positive colony, as it is rarely a colonizer
Mycobacterium abscessus
- There are no drug regimens of proven or predictable efficacy for treatment of Mycobacterium abscessus lung disease
- Multidrug regimens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression
- Surgical resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease
Non-Pulmonary Disease
Rapid Growers
- Includes Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum
- Antimicrobial selection is based on in vitro susceptibilities
- For Mycobacterium abscessus, a macrolide-based regimen is frequently used
- Surgical debridement may be necessary
Skin and Soft Tissue Infection
- 3 to 6 months for Mycobacterium marinum, 6 to 12 months for MAC
Cervical Lymphadenitis
- Mostly due to MAC
- Treated primarily by surgical excision, with a greater than 90% cure rate
- A macrolide-based regimen should be considered for patients with extensive MAC lymphadenitis or poor response to surgical therapy
Monitoring
- Depends on the antibiotics used
- Audiology for aminoglycosides
- Liver enzymes monthly for many others
References
- ^ Jennifer R. Honda, Vijaya Knight, Edward D. Chan. Pathogenesis and Risk Factors for Nontuberculous Mycobacterial Lung Disease. Clinics in Chest Medicine. 2015;36(1):1-11. doi:10.1016/j.ccm.2014.10.001.
