Non-tuberculous mycobacteria
From IDWiki
- 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 35º C
- May grow in blood culture if mycobacteremic
- Slow-growers produce colonies after more than 7 days on solid media
- MAC, M. xenopi, and M. kansasii are the three most important
- Grows optimally at 35-37º C except M. haemophilum (28-30º C) and M. xenopi (42-45º C)
- Fast-growers produce colonies within 7 days on solid media
- Media includes blood or chocolate agar, MTBC media, etc
- Species-level identifiation requires molecular tests
Species
- More than 200 species of Mycobacterium spp. that are not in M. tuberculosis complex or M. leprae
| Species | Notes |
|---|---|
| Rapid-growers | Visible in culture in <7 days |
| M. fortuitum complex | |
| M. fortuitum | |
| M. peregrinum | |
| M. porcinum | |
| M. chelonae | |
| M. abscessus | |
| M. abscessus subsp. abscessus | |
| M. abscessus subsp. bolletii | |
| M. abscessus subsp. massiliense | |
| M. smegmatis | |
| M. mucogenicum | |
| Slow-growers | Visible in culture in >7 days |
| Photochromogens | Develop pigments in light. |
| M. kansasii | Always assumed to be pathogenic, never colonizer. |
| M. marinum | Intermediate-grower (7-10 days). |
| Scotochromogens | Develop pigments in darkness. |
| M. gordonae | Intermediate-grower (7-10 days). Common tap-water contaminant. |
| M. scrofulaceum | |
| Nonchromogens | |
| M. avium complex | In HIV, rarely pulmonary and almost always disseminated. |
| M. avium | Most common subspecies. |
| M. intracellulare | |
| M. chimaera | |
| M. terrae complex | |
| M. ulcerans | |
| M. xenopi | Grows optimally at 42-45º C. |
| M. simiae | |
| M. malmoense | |
| M. szulgai | |
| M. asiaticum | |
| M. haemophilum | Grows optimally at 28-30º C. |
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 M. gordonae, M. kansasii, M. xenopi, M. simiae, MAC, and M. mucogenicum)
- 90% of patients with NTM infections have underlying pulmonary disease
- In Ontario: M. avium complex (25%), M. xenopi (10%), M. abscessus/M. chelonae, M. fortuitum
| Presentation and Species | Distribution |
|---|---|
| Pulmonary disease | |
| M. abscessus | Worldwide; may be found concomitant with MAC |
| M. avium complex | Worldwide; most common NTM pathogen in US |
| M. kansasii | US, Europe, South Africa, and coal-mining regions |
| M. malmoense | UK, northern Europe; uncommon in US |
| M. xenopi | Europe, Canada; uncommon in US; associated with pseudoinfection |
| Lymphadenitis | |
| M. avium complex | Worldwide; most common NTM pathogen in US |
| M. malmoense | UK, northern Europe (especially Scandinavia) |
| M. scrofulaceum | Worldwide; previously common, now rarely isolated in US |
| Disseminated disease | |
| M. avium complex | Worldwide; AIDS; most common NTM pathogen in US |
| M. chelonae | US; non-AIDS immunosuppressed skin lesions |
| M. haemophilum | AIDS; US, Australia; non-AIDS immunosuppressed |
| M. kansasii | AIDS; US, South Africa |
| SSTI and MSK | |
| M. abscessus | Penetrating injury |
| M. chelonae | US, associated with keratitis and disseminated disease |
| M. fortuitum | Penetrating injury, footbaths |
| M. marinum | Worldwide, fresh- and saltwater |
| M. ulcerans | Australia, tropics, Africa, Southeast Asia, not US |
| Contaminant | |
| M. gordonae | Most common NTM contaminant |
| M. haemophilum | |
| M. mucogenicum | |
| M. nonchromogenicum | |
| M. terrae complex | |
Clinical Presentation
| Syndrome | Species | Description |
|---|---|---|
| Pulmonary disease | MAC, M. kansasii, M. xenopi, M. abscessus | |
| Upper lobe cavitary | MAC, M. kansasii | Male smokers, often alcohol use, usually early 50s |
| RML/lingular nodular bronchiectasis | MAC, M. abscessus, M. absessus subsp. massiliense | Female nonsmokers, usually older than 60 |
| Localized alveolar/cavitary | M. abscessus, MAC | Prior granulomatous dz (usually TB) with bronchiectasis |
| Reticulonodular or alveolar bilateral lower lobe | M. fortuitum | Achalasia, chronic vomiting, exogenous lipoid pneumonia |
| Reticulonodular | MAC, M. abscessus subsp. abscessus, M. abscessus subsp. massiliense | Adolescents with CF, HIV-positive patients, prior bronchiectasis |
| Hypersensitivity pneumonitis | M. immunogenum, M. avium | Metal workers, indoor hot tubs |
| Cervical lymphadenitis | MAC | |
| SSTI | M. fortuitum, M. marinum, M. chelonae, M. ulcerans | |
| MSK | M. marinum, MAC, M. kansasii, M. fortuitum, M. abscessus, M. chelonae | |
| Disseminated | HIV-positive: M. avium and M. kansasii, HIV-negative: M. abscessus and M. chelonae | |
| Catheter-related | M. fortuitum, M. abscessus, M. chelonae |
Pulmonary disease
- Risk factors include COPD and CF
- Most common clinical manifestation of NTM
- Most commonly caused by MAC, M. kansasii, M. xenopi, and M. 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 M. kansasii based on only a single colony but everything else needs 2-3 positives
- Rule out TB
Diagnosis
- Requires both clinical and microbiological evidence of disease
- Clinical diagnosis
- Pulmonary symptoms, or
- Presence of nodules or cavities as seen on chest radiograph, or
- HRCT scan with multifocal bronchiectasis with multiple small nodules, and
- Exclusion of other diagnoses
- Microbiologic diagnosis
- At least 2 (of 3) expectorated sputa (or at least 1 bronchial wash or lavage) with positive cultures for NTM
- Transbronchial or other lung biopsy showing the presence of granulomatous inflammation or AFB with 1 or more sputum or bronchial washings that are culture positive for NTM.
Skin and soft tissue infections (SSTI)
- From direct inoculation
- M. abscessus, M. fortuitum, M. chelonae, M. marinum, M. ulcerans
- Dx: tissue biopsy culture (best) or culture of discharge
M. 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
M. 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
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
MAC pulmonary infection
- MAC is the prototype
- Macrolide (azithro/clarithro) 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 | Clari 1000 tiw or azi 500 tiw | Clari 500 bid or azi 250 OD |
| 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 |
M. kansasii pulmonary disease
- M. 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
M. abscessus pulmonary disease
- There are no drug regimens of proven or predictable efficacy for treatment of M. 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
- Nonpulmonary disease caused by RGM (M. abscessus, M. chelonae, M. fortuitum):
- Based on in vitro susceptibilities
- For M. abscessus, a macrolide-based regimen is frequently used
- Surgical debridement may be necessary
M. marinum SSTI
- 3 to 6 months for M. marinum, 6 to 12 months for MAC
NTM 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
