Burkholderia cepacia

Burkholderia cepacia previously known as Pseudomonas cepacia, is a nutritionally versatile, aerobic gram-negative organism, was first described in 1949 by Walter Burkholder of Cornell University, as the phytopathogen responsible for a bacterial rot of onions ¹. Burkholderia cepacia complex is a group of Gram-negative bacteria that comprise at least 20 closely related opportunistic pathogens ². Burkholderia cepacia is an organism of low virulence and is a frequent colonizer of fluids used in the hospital (eg, irrigation solutions, intravenous fluids). Burkholderia cepacia rarely causes infection in healthy hosts. Burkholderia cepacia has a particular predilection for the lung in patients with cystic fibrosis (CF) and has emerged as an important opportunistic human pathogen in hospitalized and immunocompromised patients ³. Burkholderia cepacia has emerged as a human pathogen causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. One highly transmissible strain has spread across North America and Britain, and another between hospitalized cystic fibrosis and non-cystic fibrosis patients. Ironically, Burkholderia cepacia is now being considered by agricultural microbiologists as an agent to promote crop growth. Burkholderia cepacia is inherently resistant to multiple antibiotics, can metabolize diverse substrates, and is found in soil and in moist environments.

Burkholderia cepacia symptoms

Cystic fibrosis patients

Cystic fibrosis is a recessively transmitted genetic disease that occurs in approximately 1 in 2,500 Caucasians (carrier frequency of 1 in 25). The condition is characterized by a generalized dysfunction of the exocrine glands, giving rise to a broad spectrum of clinical syndromes, especially malabsorption due to pancreatic insufficiency and chronic progressive lung disease giving rise to bronchiectasis. Burkholderia cepacia is associated with increased illness and death among cystic fibrosis patients. In the early 1980s, the organism emerged as a major threat, causing superinfection in as many as 40% of patients in some cystic fibrosis centers ⁴. While in some patients indolent pulmonary infection occurs with only gradual deterioration in lung function similar to that associated with Pseudomonas aeruginosa, approximately 35% of Burkholderia cepacia–infected patients contract accelerated pulmonary deterioration or fulminant, necrotizing pneumonia with rapidly fatal bacteremia ⁵, sometimes referred to as “cepacia syndrome” ⁶. Unlike infection with Pseudomonas aeruginosa, Burkholderia cepacia infection significantly increases death rates among cystic fibrosis patients ⁷ at all levels of lung function.

Over the last 20 years, cystic fibrosis survival rates have increased as a result of improved treatment, the median length of survival increasing from early childhood to more than 29 years. As a result, approximately one third of cystic fibrosis patients are adults. Pulmonary infection causes the most illness and ultimately more than 90% of cystic fibrosis related deaths. Burkholderia cepacia’s emergence as a pathogen coincided with social and medical grouping of cystic fibrosis patients in specialized units, clinics, and social groups. Studies subsequently demonstrated that social contact between cystic fibrosis patients was an important factor in transmission of Burkholderia cepacia ⁸.

The threat of Burkholderia cepacia infection led to severe control measures, affecting not only the treatment but also the social and family lives of cystic fibrosis patients. cystic fibrosis centers adopted stringent infection control policies, assuming that all Burkholderia cepacia isolates were highly transmissible ⁹. cystic fibrosis summer camps in North America were closed, and many lung transplant centers ceased to accept Burkholderia cepacia–infected cystic fibrosis patients as transplant candidates. Newly formed national and international associations for cystic fibrosis adults and cystic fibrosis families (providing conferences, holidays, and support groups) addressed the issue of Burkholderia cepacia transmission by abandoning many activities and adopting exclusion and segregation measures ⁹.

Numerous cystic fibrosis-associated Burkholderia cepacia epidemics have now been described, and the epidemic strains have been characterized ¹⁰. One particular highly transmissible strain, epidemically spread within and between cystic fibrosis centers on both sides of the Atlantic, carries the cblA gene ¹¹. This gene encodes for the major structural subunit of unique mucin binding cable pili ¹². These enormously long pili (radiating 2 to 4 microns) are peritrichously arranged and are intertwined to form cablelike structures that adhere to cystic fibrosis mucin ¹². This cblA+ strain has spread across Canada and has now been isolated in 50% of cystic fibrosis centers in the United Kingdom ¹³. Another strain of Burkholderia cepacia has spread among cystic fibrosis centers in four regions of France ¹⁴.

However, it has become clear that transmissibility varies markedly from strain to strain, and that most strains are not involved in epidemics but appear to be independently acquired and show no evidence of transmission. For example, in 8 years no cases of transmission were detected at the University of North Carolina cystic fibrosis center, despite clinical and social contact between patients and the absence of stringent infection control measures ¹⁵. Independent acquisition of Burkholderia cepacia with no evidence of transmission between cystic fibrosis patients was also reported from Denmark ¹⁶. Lack of transmission of some strains has also been observed between siblings with cystic fibrosis ¹⁷.

Patients without cystic fibrosis

Burkholderia cepacia was first reported as a human pathogen causing endocarditis in the 1950s. Since then the organism has caused numerous catheter-associated urinary tract infections, wound infections, and intravenous catheter–associated bacteremias. In 1971, it was reported as the causative organism of “foot rot” in U.S. troops on swamp training exercises in northern Florida; it was also isolated from troops serving in the Mekong Delta, Vietnam ¹⁸.

In the 1980s the number of nosocomial infections with Burkholderia cepacia increased markedly, with deaths particularly associated with lung infections ¹⁹.  Numerous small focal hospital outbreaks involving non-cystic fibrosis patients have usually been due to a contaminated common source, such as disinfectant preparations or intravenous solutions ²⁰. The organism’s unusually broad metabolic capabilities, which enable it to survive and proliferate in waterbased environments, probably account for its propensity to cause nosocomial outbreaks ²⁰. Because of its resistance to multiple antibiotics, once acquired, the organism can be difficult to treat.

Burkholderia cepacia is rarely found in the non-cystic fibrosis patient ²¹; however, when it is found the organism can spread to and from cystic fibrosis patients. Transmission between cystic fibrosis and non-cystic fibrosis patients has been associated with serious illness and death ²² and presents a greater nosocomial threat than previously recognized. In addition, although Burkholderia cepacia is not a common commensal organism, hospitalized patients without cystic fibrosis may harbor it and pose an infection threat to vulnerable cystic fibrosis patients. This possible source of infection may account for the known association between hospitalization and of Burkholderia cepacia infection ²³. Burkholderia cepacia may be underreported because selective media for Burkholderia cepacia, which greatly increase the yield ²⁴, are rarely used except in specimens from cystic fibrosis patients.

Burkholderia cepacia prevention

Effective infection-control measures can minimize or limit the spread of Burkholderia cepacia and other organisms in the ICU.

Recovered Burkholderia cepacia should be considered a nonpathogen unless proven otherwise.

If Burkholderia cepacia is recovered from several patients in the same area, sections of an ICU or ward can become the focus for further Burkholderia cepacia colonizations within the hospital setting.

Appropriate isolation procedures rather than antimicrobial therapy should be used to control the spread of B cepacia colonization among patients.

Burkholderia cepacia treatment

Because Burkholderia cepacia is almost always a colonizer, antimicrobial treatment is unnecessary and may be harmful unless infection is proven.

Patient-to-patient spread of Burkholderia cepacia may be minimized and/or prevented with effective infection-control measures.

Use Foley catheters only as long as necessary. If possible, avoid their use in compromised hosts predisposed to urinary tract infections (eg, patients with diabetes, SLE, multiple myeloma).

Preventing Burkholderia cepacia colonization of respiratory secretions in intubated patients who are in ICUs and on broad-spectrum antibiotics is difficult.

Burkholderia cepacia, as a non-aeruginosa pseudomonad, is usually resistant to aminoglycosides, antipseudomonal penicillins, and antipseudomonal third-generation cephalosporins and polymyxin B ²⁵.

Burkholderia cepacia is often susceptible to trimethoprim plus sulfamethoxazole (TMP-SMX), cefepime, meropenem, minocycline, and tigecycline and has varying susceptibility to fluoroquinolones.

References

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