Nontuberculous Mycobacteria Infections in Children
Introduction to Nontuberculous Mycobacteria Infections in Children
Nontuberculous mycobacteria (NTM) infections are caused by a group of environmental mycobacteria distinct from Mycobacterium tuberculosis complex and Mycobacterium leprae. These organisms are ubiquitous in the environment and can cause a variety of clinical syndromes in children, ranging from localized skin and soft tissue infections to disseminated disease.
NTM infections in children present unique challenges in diagnosis and management due to their diverse clinical manifestations and the need for prolonged antimicrobial therapy. Understanding the epidemiology, clinical presentation, and treatment options is crucial for pediatricians and infectious disease specialists.
Epidemiology of NTM Infections in Children
The incidence of NTM infections in children varies globally and is influenced by several factors:
- Geographic location: Higher rates are observed in warmer, humid climates.
- Environmental exposure: Soil, water, and animals are common sources.
- Age: Peak incidence occurs between 1-5 years of age.
- Immunocompetence: Increased risk in immunocompromised children.
Common NTM species causing infections in children include:
- Mycobacterium avium complex (MAC)
- Mycobacterium abscessus
- Mycobacterium marinum
- Mycobacterium fortuitum
The prevalence of specific NTM species varies by geographic region and clinical syndrome.
Etiology of NTM Infections in Children
NTM infections are caused by environmental mycobacteria that are not members of the Mycobacterium tuberculosis complex. These organisms have the following characteristics:
- Acid-fast bacilli
- Environmental saprophytes found in soil and water
- Capable of forming biofilms
- Resistant to many common disinfectants
Transmission to humans typically occurs through:
- Inhalation of aerosolized organisms
- Ingestion of contaminated water or food
- Direct inoculation through skin breaks or surgical procedures
Risk factors for NTM infections in children include:
- Primary or acquired immunodeficiencies
- Chronic lung diseases (e.g., cystic fibrosis)
- Structural abnormalities (e.g., pectus excavatum)
- Recent surgical procedures or trauma
- Foreign body presence (e.g., central venous catheters)
Clinical Presentation of NTM Infections in Children
NTM infections in children can manifest in various forms, depending on the site of infection and the causative species. Common clinical presentations include:
1. Lymphadenitis
- Most common form in immunocompetent children
- Typically unilateral and cervical
- Presents as painless, enlarging lymph node(s)
- May progress to fluctuance and spontaneous drainage
2. Skin and Soft Tissue Infections
- Often follows trauma or surgical procedures
- Presents as nodules, abscesses, or chronic wounds
- M. marinum infections associated with aquatic exposure
3. Pulmonary Infections
- More common in children with underlying lung disease
- Symptoms include chronic cough, sputum production, and fatigue
- Radiographic findings may mimic tuberculosis
4. Disseminated Disease
- Occurs primarily in severely immunocompromised children
- Presents with fever, weight loss, lymphadenopathy, and organomegaly
- May involve multiple organ systems
5. Catheter-Related Infections
- Associated with long-term central venous catheters
- Presents with fever and exit site inflammation
Diagnosis of NTM Infections in Children
Diagnosing NTM infections in children requires a combination of clinical suspicion, appropriate specimen collection, and laboratory testing. The diagnostic approach includes:
1. Clinical Assessment
- Detailed history and physical examination
- Evaluation of risk factors and potential exposures
2. Imaging Studies
- Ultrasonography for lymphadenitis
- Chest radiography and CT for pulmonary infections
- MRI for deep tissue infections or CNS involvement
3. Microbiological Studies
- Acid-fast bacilli (AFB) smear microscopy
- Mycobacterial culture on appropriate media
- Species identification using molecular methods (e.g., PCR, DNA sequencing)
4. Histopathology
- Biopsy of affected tissues showing granulomatous inflammation
- Special stains for AFB (e.g., Ziehl-Neelsen, Fite)
5. Immunological Testing
- Interferon-gamma release assays (IGRAs) to exclude tuberculosis
- Evaluation for underlying immunodeficiencies
6. Drug Susceptibility Testing
- Essential for guiding antimicrobial therapy
- May be genotypic or phenotypic
It's important to note that diagnosis can be challenging due to the slow growth of NTM in culture and the need for specialized laboratory techniques. A high index of suspicion and close collaboration with microbiology and pathology departments are crucial for accurate diagnosis.
Treatment of NTM Infections in Children
Management of NTM infections in children often requires a multidisciplinary approach involving pediatric infectious disease specialists, surgeons, and pulmonologists. Treatment strategies depend on the site of infection, causative species, and underlying host factors.
1. General Principles
- Prolonged antimicrobial therapy (often 6-12 months or longer)
- Combination therapy to prevent resistance development
- Regular monitoring for drug toxicities and clinical response
2. Lymphadenitis
- Complete surgical excision is often curative for localized disease
- Antimicrobial therapy may be considered for extensive disease or recurrence
- Observation may be appropriate in select cases
3. Skin and Soft Tissue Infections
- Combination of surgical debridement and antimicrobial therapy
- Common agents: clarithromycin, azithromycin, ethambutol, rifampin
- Duration typically 3-6 months, guided by clinical response
4. Pulmonary Infections
- Multidrug regimen based on susceptibility testing
- For MAC: azithromycin/clarithromycin, ethambutol, rifampin
- For M. abscessus: combination of parenteral and oral agents
- Treatment duration often 12-18 months or longer
5. Disseminated Disease
- Aggressive multidrug therapy
- Management of underlying immunodeficiency
- Prolonged treatment course, often >12 months
6. Catheter-Related Infections
- Catheter removal when possible
- Antimicrobial therapy based on susceptibility testing
7. Adjunctive Therapies
- Interferon-gamma for patients with interferon pathway defects
- Inhaled amikacin for refractory pulmonary disease
- Therapeutic drug monitoring to optimize dosing
Treatment of NTM infections in children can be challenging due to the need for prolonged therapy, potential drug toxicities, and the risk of antimicrobial resistance. Close monitoring and adjustment of therapy based on clinical response are essential for optimal outcomes.
Prognosis of NTM Infections in Children
The prognosis of NTM infections in children varies depending on several factors:
Factors Influencing Prognosis
- Site and extent of infection
- Causative NTM species
- Underlying host factors (e.g., immune status, comorbidities)
- Timeliness of diagnosis and initiation of appropriate therapy
- Adherence to treatment regimens
Prognosis by Clinical Presentation
- Lymphadenitis:
- Excellent prognosis with complete surgical excision
- Spontaneous resolution may occur in some cases
- Recurrence rates are low with appropriate management
- Skin and Soft Tissue Infections:
- Generally good prognosis with combined surgical and medical management
- Chronic or recurrent infections may occur in some cases
- Pulmonary Infections:
- Variable prognosis depending on underlying lung disease
- Cure rates of 30-50% in children with cystic fibrosis
- Higher success rates in children without underlying lung disease
- Disseminated Disease:
- Generally poor prognosis without effective immune reconstitution
- Mortality rates can be high in severely immunocompromised patients
- Catheter-Related Infections:
- Good prognosis with catheter removal and appropriate antimicrobial therapy
- Recurrence possible if catheter cannot be removed
Long-Term Considerations
- Potential for chronic lung disease in pulmonary NTM infections
- Need for long-term follow-up to monitor for recurrence
- Importance of addressing underlying risk factors to prevent reinfection
Overall, with appropriate diagnosis and management, many children with NTM infections have favorable outcomes. However, some may experience chronic or recurrent disease, emphasizing the need for individualized treatment approaches and long-term follow-up.
Nontuberculous Mycobacteria Infections in Children
- What are nontuberculous mycobacteria (NTM)?
Environmental mycobacteria that can cause disease in humans but are distinct from M. tuberculosis complex - Which age group of children is most commonly affected by NTM infections?
Children under 5 years old - What is the most common clinical presentation of NTM infection in immunocompetent children?
Cervical lymphadenitis - Which NTM species is most frequently associated with lymphadenitis in children?
Mycobacterium avium complex (MAC) - What is the typical appearance of NTM lymphadenitis?
Unilateral, painless, gradually enlarging lymph node, often with violaceous skin discoloration - How are NTM typically acquired in the environment?
Through inhalation, ingestion, or direct inoculation from soil, water, or other environmental sources - What is Lady Windermere syndrome?
A form of NTM lung disease typically affecting elderly women, characterized by lingular and right middle lobe bronchiectasis - Which diagnostic test is considered the gold standard for NTM infection?
Culture and species identification from affected tissue or body fluid - What imaging technique is commonly used to evaluate NTM lymphadenitis?
Ultrasound - What is the typical duration of antibiotic treatment for NTM lymphadenitis?
3-6 months - Which surgical procedure is often recommended for localized NTM lymphadenitis?
Complete excision of the affected lymph node - What is hot tub lung?
A hypersensitivity pneumonitis caused by inhalation of NTM, particularly M. avium complex, from contaminated water sources - Which NTM species is most commonly associated with skin and soft tissue infections?
Mycobacterium marinum - What is fish tank granuloma?
A skin infection caused by M. marinum, typically acquired through contact with contaminated aquarium water - Which group of children are at higher risk for disseminated NTM infections?
Children with primary immunodeficiencies, particularly those affecting the IL-12/IFN-γ axis - What is the most common radiographic finding in pulmonary NTM disease?
Nodular bronchiectasis - Which NTM species is known for causing rapidly growing mycobacterial infections?
Mycobacterium abscessus - What is the role of interferon-gamma in NTM infections?
It plays a crucial role in host defense against mycobacterial infections, and defects in its pathway increase susceptibility to NTM - How does the treatment of NTM infections differ from tuberculosis treatment?
NTM infections often require longer treatment durations and combinations of antibiotics specific to the identified species - What is the significance of biofilm formation in NTM infections?
Biofilms contribute to antibiotic resistance and persistence of infection, particularly in device-associated infections - Which NTM species is most commonly associated with hypersensitivity pneumonitis?
Mycobacterium immunogenum - What is the role of macrolides in treating NTM infections?
Macrolides are often the cornerstone of treatment for many NTM infections due to their antimicrobial and immunomodulatory effects - How does cystic fibrosis predispose children to NTM infections?
The thick mucus in CF lungs provides an ideal environment for NTM growth and impairs clearance mechanisms - What is the significance of "rough" and "smooth" colony morphotypes in M. abscessus infections?
Rough morphotypes are associated with increased virulence and biofilm formation, while smooth morphotypes are generally less virulent - How does the American Thoracic Society define NTM pulmonary disease?
It requires clinical, radiographic, and microbiological criteria to be met, including multiple positive cultures - What is the role of molecular methods in diagnosing NTM infections?
They allow for rapid species identification and can detect genetic mutations associated with antibiotic resistance - Which NTM species is most commonly associated with cervical lymphadenitis in children?
Mycobacterium avium - What is the "tap water syndrome" in the context of NTM infections?
Refers to NTM infections acquired from contaminated household water sources, particularly in immunocompromised individuals - How does HIV infection impact the risk and presentation of NTM infections in children?
HIV-infected children are at higher risk for disseminated NTM infections, particularly with low CD4 counts - What is the role of susceptibility testing in managing NTM infections?
It guides the selection of appropriate antibiotics, as NTM species have variable susceptibility patterns
Further Reading
- Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases
- Nontuberculous Mycobacterial Disease in Children – Epidemiology, Diagnosis & Management at a Tertiary Center
- An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases
- The Epidemiology of Nontuberculous Mycobacterial Lung Disease in the United States
- Nontuberculous Mycobacterial Infections in Cystic Fibrosis
