Discussion

Burkholderia cepacia complex (Bcc) and Cystic Fibrosis (CF)

Burkholderia cepacia complex (Bcc) is a gram negative bacillus, first described in the 1950s as the causative agent of onion soft rot.[1] It was first reported in sputum from cystic fibrosis (CF) patients in the 1970s.[2,3] In the 1980s, several CF centres documented a dramatic increase in the prevalence of Bcc in their institution.[4,5] Of note, there was significant centre-to-centre variation, with larger centres reporting increased incidence of infection.[6]

Early reports described three potential disease courses of patients infected with Bcc.[4,5] The first was chronic, asymptomatic carriage of Bcc. The second was progressive deterioration, with rapidly declining forced expiratory volume in one second (FEV1). The final was a rapid, fatal, fulminant pulmonary infection, termed Cepacia Syndrome. Perhaps most concerning, case-control studies documented a dramatic increase in overall mortality once Bcc was isolated from a patient (34% over 3.5 years as compared to 20% of controls).[7]

Although Bcc is a ubiquitous environmental pathogen, there was broad geographic variation in the number of cases, which led to investigation into possible modes of acquisition. Increased risk of infection was linked to increasing severity of CF or increasing age.[8,9] Having a sibling infected with Bcc, or having a recent hospitalization, dramatically increased a patient’s risk of acquiring Bcc.[9] Numerous epidemiologic and ribotyping studies went on to demonstrate person-to-person transmission of Bcc.[10,11,12,13,14] This has led to recommendations for segregation of patients infected with Bcc, in both hospital and outpatient settings.[9]

However, over the last decade, it has become apparent that bacterial isolates identified as B. cepacia actually included bacteria with marked genetic diversity.[15.16] Thus, the Bcc organisms have been reclassified into separate species.[15,17] In Canada, B. cenocepacia (genomovar III) accounts for 80% of patients infected with Bcc.[16] One particular strain of this organism, ET-12, has been responsible for epidemics in both Canada and the UK.[18]

Genomovar	Binomial Designation
I	B. cepacia
II	B. multivorans
III	B. cenocepacia
IV	B. stabilis
V	B. vietnamiensis
VI	B. dolosa
VII	B. ambifaria
VIII	B. anthina
IX	B. pyrrocinia

From the early stages of lung transplantation, it was noted that there was a wide variation in survival among CF patients between transplant centres.[15] The reason for this discrepancy became clear upon reviewing the Toronto transplant experience. A recent study by this group documented a one-year survival of 67% in the patients infected with Bcc, as compared to 92% in the non-Bcc patients.[19] These data led to some centres excluding patients infected with Bcc from lung transplantation.[20] However, over the same time period, groups from the UK and US documented no significant difference in survival among patients with Bcc from the rest of their patient population.[21,22,23]

It became suspected that variations in Bcc genomovar were underlying the survival differential.[24] Groups from the US and France have recent published their experience with lung transplantation in Bcc-infected patients.[17,25] Both groups documented a dramatic decrease in survival among B. cenocepacia-infected patients as compared to patients infected with other Bcc. The Toronto program is now using a modified protocol of immunosuppression and antimicrobial coverage post-transplant for patients infected with B. cenocepacia, with the goal of modifying outcomes.[19] As our knowledge of Bcc and lung transplantation advance, it remains to be seen how the interplay between patient and organism will affect long-term outcomes.

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