Burkholderia

Burkholderia species are gram-negative bacilli with 2 clinically relevant pathogens: B. pseudomallei (causing melioidosis) and B. cepacia complex (causing opportunistic infections). Melioidosis is commonly seen in Asia and Australia. Infection is transmitted by contact with contaminated soil or water (via skin wounds). The disease affects multiple systems, and can present with pneumonia, encephalomyelitis, and skin abscesses. Diagnosis is by culture of specimen (depending on the organ involved). Treatment requires an initial intensive antibiotic therapy followed by prolonged eradication therapy. Burkholderia cepacia complex (BCC) generally affects immunocompromised individuals such as those with cystic fibrosis (CF). It can be transmitted from person to person or through contaminated devices. While BCC is a rare infection, it is important to diagnose, as BCC is multi-drug resistant and infection is a relative contraindication to lung transplantation.

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Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

Image by Lecturio.

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
Image: “” by . License:

Burkholderia pseudomallei colonies on a blood agar plate

Image: “Burkholderia pseudomallei 01” by CDC. License: Public Domain

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
B. cepacia complex infection

B. cepacia complex infection:
Chest X-ray of a patient showing right-sided pneumonia. Tracheal aspirate and blood cultures grew B. cepacia.

Image: “Cepacia Syndrome in a Non-Cystic Fibrosis Patient” by Hauser N, Orsini J. License: CC BY 3.0

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.

References

  1. Currie, B., Anstey, N. (2021). Melioidosis: Epidemiology, clinical manifestations and diagnosis. UpToDate. Retrieved May 28, 2021, from https://www.uptodate.com/contents/melioidosis-epidemiology-clinical-manifestations-and-diagnosis
  2. Currie, B., Anstey, N. (2021). Melioidosis: Treatment and prevention. UpToDate. Retrieved May 28, 2021, from https://www.uptodate.com/contents/melioidosis-treatment-and-prevention
  3. Currie, B., Ward, L., Cheng, A. (2010). The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl Trop Dis. 4:e900.
  4. Mahmood, S., Ahmed, S. (2018). Burkholderia cepacia. Medscape. Retrieved May 29, 2021, from https://emedicine.medscape.com/article/237122-overview
  5. Riedel, S., et al. (Eds.). (2019). Pseudomonas, acinetobacter, burkholderia, and stenotrophomonas. In Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed.) https://accessmedicine.mhmedical.com/content.aspx?bookid=2629&sectionid=217771138 
  6. Torok, E., Moran, E., Cooke, F. (2009). Oxford Handbook of Infectious Diseases and Microbiology. Oxford University Press. 
  7. Zaas, A., Palmer, S., Messina, J. (2021). Bacterial infections following lung transplantation. UpToDate. Retrieved May 28, 2021, from https://www.uptodate.com/contents/bacterial-infections-following-lung-transplantation

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