Burkholderia

Classification

Characteristics

Basic features

Burkholderia:

• Gram-negative bacillus
• Obligately aerobic
• Motile (with polar flagella)
• Non-lactose fermenting
• Oxidase positive
• Culture: grows in standard bacteriologic media

Clinically significant species:

• Burkholderia pseudomallei:
  • Widely distributed in soil and fresh surface water in endemic regions 
  • Cause of melioidosis
• Burkholderia cepacia complex (BCC): group of bacteria that grows in water, soil, plants, animals, and decaying vegetable materials

Burkholderia pseudomallei

Etiology and epidemiology

• Associated with melioidosis (also known as Whitmore disease)
• Endemic areas:
  • Southeast Asia
  • Northern Australia
  • South Asia (including India)
  • China
• Rare in the United States
• Seasonal peak in wet (rainy) seasons

Pathophysiology

Transmission:

• Contact with contaminated water or soil, especially through skin wounds (predominant mode)
• Inhalation of bacteria in dust and aerosols
• Ingestion of bacteria in contaminated foods or water
• Animal-to-human and human-to-human transmissions are rare.

Host risk factors include:

• Diabetes
• Alcohol abuse
• Liver disease
• Renal disease
• Thalassemia
• Kava consumption
• Immunosuppressive condition (e.g., cancer)
• Chronic lung disease including cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD)

Clinical presentation

• Incubation period: 
  • 1–21 days
  • Influenced by a dose of inoculation, host risk factors, mode of transmission
• Most patients are asymptomatic.
• Presentation can be:
  •  Acute:
    • Majority of cases
    • Symptoms for < 2 months
  • Chronic: symptoms for > 2 months

Symptoms can present in various systems:

• Bacteremia or sepsis
• Focal abscess in organs (i.e., liver, kidney, spleen)
• Respiratory:
  • Fever
  • Cough
  • Chest pain
  • Respiratory distress
  • Chronic symptoms: productive cough, hemoptysis, night sweats (similar to tuberculosis)
• Dermatologic:
  • Skin changes (ulceration, abscess) that fail to resolve with antibiotic treatment
  • Rarely develops cellulitis
• Genitourinary:
  • Fever with dysuria
  • Urinary retention
  • Tender prostate
• Joints:
  • Septic arthritis
  • Osteomyelitis
• Neurologic (encephalomyelitis):
  • Cerebellar signs
  • Cranial nerve palsies
  • Upper motor neuron weakness

Diagnosis

Diagnostic tests:

• Culture of specimens that can include:
  • Blood
  • Sputum 
  • Urine
  • Swabs from rectum, skin wound/ulcer/abscess, throat
• Gram stain of specimen(s):
  • Gram-negative bacilli
  • Bipolar staining with a “safety pin” appearance
• Serology: limited use
• Antigen and DNA detection: Most are not yet commercially available.

Additional tests:

• Chest X-ray findings vary:
  • Infiltrates
  • Pleural effusion
  • Lobar consolidation
  • Cavitation and abscesses with fluid level
  • Chronic findings: fibrosis with nodular, cavitating, or streaky infiltrates
• CT scan or MRI:
  • Evaluate abdominal multifocal infections
  • Check prostate

Management

Resistant to: 

• Penicillin/ampicillin
• 1st- and 2nd-generation cephalosporins
• Gentamicin
• Tobramycin
• Streptomycin 

Initial regimen(s) depends on severity of illness and system(s) affected: 

• Stable (non-critical) without CNS infection: ceftazidime
• Critically ill: 
  • Imipenem
  • Meropenem
• CNS infection: meropenem (higher dose)
• Adjunctive antibiotic: trimethoprim-sulfamethoxazole (TMP-SMX)
• Additional management:
  • Abscess drainage
  • Supportive care (e.g., fluid management)
  • Recombinant human granulocyte-colony stimulating factor (G-CSF) for those in septic shock

Eradication treatment:

• After the initial phase of intensive treatment, additional antibiotic intake is recommended to reduce relapse.
• In general, duration is at least 3–6 months (depending on type of infection).
• Some require > 6 months (i.e., arterial infection, often a mycotic aneurysm).
• Options:
  • Oral TMP-SMX with folic acid
  • Oral doxycycline (alternative)

Prevention:

• Avoid skin exposure to soil and water, especially in the wet season.
• High-risk individuals (e.g., patients with CF) should avoid travel in endemic areas during the wet season.
• In a bioterrorism event or accidental laboratory exposure, post-exposure prophylaxis (PEP) with TMP-SMX is recommended.

Burkholderia cepacia Complex

Etiology and epidemiology

BCC:

• A group of different species that make up the complex
• Opportunistic human pathogen
• Species commonly isolated in the sputum of patients with CF:
  • B. multivorans
  • B. cenocepacia 

Epidemiology:

• Rare infection and not commonly found in an ambulatory setting
• In the United States, reports of infection and contamination include: 
  • In 2004: nosocomial infections from B. cepacia due to contaminated sublingual probes
  • In 2004: recall of over-the-counter nasal spray due to contamination
  • In 2005: pneumonia from contaminated mouthwash

Pathophysiology

Transmission:

• Device and/or medicine contamination
• Contamination of water and environmental sources
• Contact with contaminated surfaces
• Person-to-person contact

Medical devices that can be contaminated and produce infection:

• Pressure monitoring devices 
• Indwelling Foley catheters, urometers, irrigation fluids
• IVs, central catheters, IV fluids
• Respiratory equipment (respirator tubing condensate, ultrasonic nebulizers, inhalation medications)

Host risk factors:

• Generally with low virulence and presents minimal risk for healthy people
• Those at risk:
  • Individuals with weakened immune systems 
  • Individuals with CF or chronic lung disease (COPD, bronchiectasis, chronic granulomatous disease)

Clinical presentation

Most infected people have no symptoms. Those with symptoms can have:

• Low-grade fever
• Pneumonia
• Chronic lung infection in CF:
  • Decreases survival
  • Related to recurrent, severe infections
• Other manifestations depend on organ system involved.

Diagnosis

• Culture of body fluids (in organ affected)
  • Selective media containing colistin (e.g., B. cepacia selective agar): recommended for sputum of patients with CF
  • Growth is slow, and may take 3 days.
• Additional testing (e.g., imaging) done depending on system involved

Management

• Known for being multi-drug resistant
• Antibiotic options (multiple agents used):
  • Co-trimoxazole
  • Ceftazidime
  • Minocycline
  • Carbapenems
•  Screen all patients with CF for B. cenocepacia prior to transplantation, as colonization is a relative contraindication for lung transplantation.