Burkholderia Cepacia Infections in Children

Introduction

Burkholderia cepacia complex (Bcc) is a group of at least 20 closely related species of gram-negative bacteria that can cause severe infections in children, particularly those with cystic fibrosis (CF) or other underlying health conditions. These opportunistic pathogens are known for their intrinsic antibiotic resistance and ability to cause both acute and chronic infections.

B. cepacia infections pose significant challenges in pediatric care due to their potential for rapid clinical deterioration, especially in CF patients, and the limited treatment options available. Understanding the complexities of these infections is crucial for healthcare providers managing pediatric patients at risk.

Epidemiology

Burkholderia cepacia complex infections are particularly prevalent in specific pediatric populations:

Cystic Fibrosis patients: Bcc colonizes 2-8% of CF patients, with rates varying by geographic region and care center.
Chronic Granulomatous Disease (CGD) patients: Bcc is a significant pathogen in this population.
Immunocompromised children: Those with primary immunodeficiencies or undergoing immunosuppressive therapy.
Hospitalized patients: Particularly those in intensive care units or with prolonged hospital stays.
Neonates: Rare cases of neonatal infections have been reported, often associated with contaminated medical equipment or solutions.

Transmission of Bcc can occur through:

Person-to-person contact: Especially among CF patients.
Environmental sources: Bcc can survive in water, soil, and on surfaces for extended periods.
Contaminated medical devices or products: Including nebulizers, medications, and disinfectants.

The prevalence of different Bcc species varies, with B. cenocepacia and B. multivorans being the most common in CF patients in many regions. However, the distribution can change over time and differ geographically.

Pathogenesis

Burkholderia cepacia complex employs various virulence factors to establish infection:

Adhesins: Facilitate attachment to host cells (e.g., pili, adhesive proteins).
Biofilm formation: Protects bacteria from host defenses and antibiotics.
Quorum sensing: Allows coordinated gene expression in bacterial populations.
Siderophores: Enhance iron acquisition in the host environment.
Type III and Type VI secretion systems: Inject effector proteins into host cells.
Lipopolysaccharide (LPS): Contributes to inflammatory response and antibiotic resistance.
Proteases and lipases: Cause tissue damage and aid in nutrient acquisition.

The pathogenesis of Bcc infections often involves:

Initial colonization of the respiratory tract, particularly in CF patients.
Evasion of host immune responses, including intracellular survival in macrophages.
Formation of biofilms, contributing to chronic infection.
Potential for rapid dissemination leading to "cepacia syndrome" in some CF patients.

In CF patients, Bcc can interact with Pseudomonas aeruginosa, potentially enhancing virulence and antibiotic resistance of both pathogens.

Clinical Manifestations

Burkholderia cepacia complex infections in children can present with a wide range of clinical manifestations:

Respiratory Tract Infections

Chronic colonization in CF: May lead to accelerated decline in lung function.
Pneumonia: Fever, increased cough, dyspnea, and sometimes hemoptysis.
"Cepacia syndrome": Rapid, severe deterioration with necrotizing pneumonia and septicemia, primarily in CF patients.

Bloodstream Infections

Can occur in both CF and non-CF patients, especially those with indwelling catheters.
Symptoms include fever, chills, and potential progression to septic shock.

Skin and Soft Tissue Infections

Cellulitis, abscesses, or wound infections, particularly in CGD patients.
May present with erythema, swelling, and purulent discharge.

Urinary Tract Infections

Less common, but can occur, especially in patients with urological abnormalities.
Symptoms may include fever, dysuria, and flank pain.

Other Manifestations

Osteomyelitis: Can occur in CGD patients or following trauma.
Central nervous system infections: Rare but severe, including meningitis or brain abscesses.
Otitis media: Particularly in children with anatomical abnormalities of the ear.

Chronic Granulomatous Disease-specific Manifestations

Lymphadenitis: Swollen, sometimes suppurative lymph nodes.
Liver abscesses: Can be difficult to treat and may require surgical intervention.

Diagnosis

Accurate diagnosis of Burkholderia cepacia complex infections is crucial for appropriate management:

Clinical Suspicion

Based on patient risk factors (e.g., CF, CGD) and clinical presentation.
Consider Bcc in CF patients with unexplained clinical deterioration.

Microbiological Culture

Gold standard for diagnosis.
Specimens may include sputum, blood, wound swabs, or other relevant clinical samples.
Selective media (e.g., B. cepacia selective agar) may be required for isolation from polymicrobial samples.

Species Identification

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.
Molecular methods: PCR and sequencing of specific genes (e.g., recA, 16S rRNA).

Antimicrobial Susceptibility Testing

Essential due to high levels of intrinsic and acquired resistance.
May require specialized methods (e.g., broth microdilution) for accurate results.

Molecular Diagnostics

PCR-based methods can provide rapid identification and species differentiation.
Useful for epidemiological investigations and detecting antibiotic resistance genes.

Imaging Studies

Chest X-ray or CT scan for suspected pneumonia or pulmonary exacerbations in CF.
CT or MRI for suspected deep-seated infections (e.g., brain abscesses, osteomyelitis).

Biomarkers

Elevated inflammatory markers (e.g., CRP, ESR) may indicate active infection.
Not specific to Bcc but can help monitor response to treatment.

Treatment

Treatment of Burkholderia cepacia complex infections in children is challenging due to intrinsic antibiotic resistance:

Antibiotic Therapy

Empiric therapy: Often includes combination therapy with two or more antibiotics.
Targeted therapy: Based on antimicrobial susceptibility testing results.
Common antibiotics used (often in combination):
- Trimethoprim-sulfamethoxazole (TMP-SMX): Often a first-line agent
- Ceftazidime or meropenem
- Minocycline or doxycycline
- Chloramphenicol
- Tobramycin (inhaled for respiratory infections in CF)

Duration of Therapy

Typically 2-4 weeks for acute infections.
May be extended for chronic or deep-seated infections.
In CF patients, long-term suppressive therapy may be considered.

Supportive Care

Respiratory support: Oxygen therapy, airway clearance techniques, mechanical ventilation if needed.
Nutritional support: Particularly important in CF patients.
Management of underlying conditions (e.g., optimizing CF care, managing immunosuppression in CGD).

Source Control

Removal of infected catheters or other foreign bodies when possible.
Drainage of abscesses or other collections.

Monitoring and Follow-up

Regular assessment of clinical response and potential adverse effects of antibiotics.
Repeat cultures to ensure eradication of infection or monitor chronic colonization.

Special Considerations

CF patients: May require aggressive combination therapy and consideration for lung transplantation in severe cases.
CGD patients: Prophylactic antibiotics (usually TMP-SMX) are often used to prevent Bcc and other infections.
Multidrug-resistant infections: May necessitate use of less conventional antibiotics or combination therapies.

Prevention

Preventing Burkholderia cepacia complex infections in children involves several strategies:

Infection Control Measures

Hand hygiene: Proper hand washing and use of alcohol-based hand sanitizers.
Contact precautions: For patients known to be colonized or infected with Bcc.
Segregation policies: In CF clinics, separating Bcc-positive patients from Bcc-negative patients.
Environmental cleaning: Regular disinfection of high-touch surfaces and medical equipment.

Device and Equipment Management

Proper cleaning and disinfection of respiratory equipment (e.g., nebulizers).
Use of sterile water for respiratory treatments.
Avoiding sharing of personal items among CF patients.

Surveillance

Regular screening of CF patients for Bcc colonization.
Molecular typing of Bcc isolates to detect potential outbreaks.

Patient Education

Teaching proper hygiene practices to patients and families.
Educating about the importance of infection control measures, especially in CF patients.

Antimicrobial Stewardship

Judicious use of antibiotics to prevent the emergence of resistant strains.
Implementation of hospital-wide antibiotic stewardship programs.

Prophylaxis

In CGD patients, use of prophylactic antibiotics (usually TMP-SMX) to prevent Bcc infections.

Research and Development

Ongoing research into potential vaccines or immunotherapies against Bcc.
Development of new antimicrobial agents or treatment strategies.

Objective QnA: Burkholderia Cepacia Infections in Children

What is Burkholderia cepacia?
A group of closely related bacterial species known as the Burkholderia cepacia complex (Bcc)
Which group of children is most at risk for B. cepacia infections?
Children with cystic fibrosis (CF)
Can B. cepacia infect children without cystic fibrosis?
Yes, especially immunocompromised children or those with chronic granulomatous disease
What are the main modes of transmission for B. cepacia in healthcare settings?
Person-to-person transmission, contaminated medical equipment, and contaminated medications or disinfectants
Why is B. cepacia particularly concerning for children with cystic fibrosis?
It can cause rapid decline in lung function and is associated with increased morbidity and mortality
What is "cepacia syndrome"?
A rapid, severe deterioration in lung function accompanied by bacteremia and sepsis in CF patients infected with B. cepacia
How is B. cepacia typically diagnosed?
Through culture of respiratory specimens on selective media, followed by species identification
What is the role of PCR in diagnosing B. cepacia infections?
PCR can provide rapid and specific identification of B. cepacia complex species
Why is B. cepacia difficult to treat?
It is inherently resistant to many antibiotics and can develop resistance during treatment
What is the recommended approach to antibiotic treatment for B. cepacia infections?
Combination therapy based on susceptibility testing, often including multiple antibiotics
Can B. cepacia form biofilms?
Yes, B. cepacia can form biofilms, contributing to antibiotic resistance and persistent infections
What is the significance of B. cepacia in non-CF bronchiectasis?
It can colonize and infect patients with non-CF bronchiectasis, potentially leading to lung function decline
Can B. cepacia cause bloodstream infections in children?
Yes, especially in immunocompromised children or those with indwelling vascular devices
What is the role of environmental sampling in B. cepacia outbreaks?
It helps identify potential sources of infection and guide infection control measures
How does B. cepacia affect lung transplantation in CF patients?
Pre-transplant B. cepacia infection is associated with poorer post-transplant outcomes
Can B. cepacia cause skin and soft tissue infections in children?
Yes, particularly in immunocompromised children or following traumatic injuries
What is the significance of different B. cepacia complex species in CF patients?
Some species, like B. cenocepacia, are associated with worse clinical outcomes
How does B. cepacia evade the host immune response?
By surviving intracellularly, forming biofilms, and producing various virulence factors
What is the role of nebulized antibiotics in treating B. cepacia infections in CF patients?
Nebulized antibiotics can help suppress B. cepacia and improve lung function
Can B. cepacia cause meningitis in children?
Rarely, B. cepacia can cause meningitis, especially in immunocompromised children
What is the significance of B. cepacia in chronic granulomatous disease (CGD)?
B. cepacia is a significant pathogen in CGD patients, causing severe pneumonia and sepsis
How does colonization with B. cepacia affect the CF lung microbiome?
B. cepacia can alter the lung microbiome diversity and interact with other pathogens
What is the role of quorum sensing in B. cepacia virulence?
Quorum sensing regulates virulence factor production and biofilm formation
Can B. cepacia cause urinary tract infections in children?
Yes, although it is an uncommon cause of UTIs in children
What is the significance of B. cepacia in neonatal infections?
B. cepacia can cause severe infections in neonates, particularly in the NICU setting
How does B. cepacia affect wound healing?
It can impair wound healing and cause chronic wound infections
What is the role of epidemiological typing in B. cepacia infections?
It helps identify transmission patterns and outbreak sources in healthcare settings
Can B. cepacia cause osteomyelitis in children?
Rarely, B. cepacia can cause osteomyelitis, especially following traumatic injuries
What is the significance of B. cepacia in contaminated medications?
Contaminated medications have been sources of outbreaks, particularly in vulnerable populations
How does climate change potentially affect the distribution of B. cepacia?
Changes in soil ecology and water systems may alter the environmental prevalence of B. cepacia
What is the role of inhaled aztreonam in treating B. cepacia infections in CF patients?
Inhaled aztreonam can improve lung function and reduce exacerbations in some CF patients with B. cepacia
Can B. cepacia cause endocarditis in children?
Rarely, B. cepacia can cause endocarditis, particularly in children with indwelling vascular devices
What is the significance of genomic islands in B. cepacia virulence?
Genomic islands contain virulence genes that contribute to pathogenicity and host adaptation
How does B. cepacia affect neutrophil function?
It can modulate neutrophil function, potentially contributing to excessive inflammation in CF lungs