**13.** *Burkholderia cepacia* **complex**

Long mistaken for a *Pseudomonas*, *Burkholderia* species were identified more accurately in the 1980s and 1990s as diagnostic techniques improved. Now recognised as perhaps the most virulent pathogens in CF, they present a major treatment challenge. The *Burkholderia Cepacia Complex* (BCC) is comprised of at least 17 distinct species of gram-negative bacteria. Termed Genomovars, these species vary in prevalence and apparent virulence. The most common BCC strains identified are *B.Cenocepacia* and *B.Multivorans*. Evidence from 2002 revealed a four-fold mortality risk in patients colonised with epidemic *B.Cenocepacia*, associated with a more rapid rate of lung function decline versus others (FEV1 -1.9% vs. -0.3% per annum) [66]. Further data from 2004 showed *B.Cenocepacia* was associated with a statistically significant higher rate of lung function decline (-140 ml/year vs. -32 ml/year (p=0.01)) and reduction in BMI when compared to PA and *B.Multivorans* [67]. Whilst evidence is mounting that specific BCC genomovars have a hierarchy of virulence with *B.Cenocepacia* associated with the highest morbidity, it is worth noting that progressive disease can be caused by a multitude of strains. "*Cepacia Syndrome*", a constellation of sepsis, fevers, and leucocytosis and fulminant decline most often resulting in death, has been described with genomovars other than *B.Cenocepacia* [68]. The true determinant of virulence may best be assessed by identification of specific epidemic strains within distinct genomovars. Moreover, strains associated with poor outcomes in the native lungs of CF sufferers may not cause the worst outcomes in post-transplant patients. A 2008 study assessing mortality in CF patients on transplant waiting list and posttransplant revealed a higher waiting-list five year mortality in *B.Multivorans* and non-epidemic strain *B.Cenocepacia* carriers than those with epidemic strains of *B.Cenocepacia*. Furthermore, 5 year post-transplant mortality was highest in the non-epidemic *B.Cenocepacia* cohort and carriers of *Burkholderia Gladioli*, an organism not included in the *BCC* group, and generally considered less relevant as a CF pathogen [69]. Clearly a deeper understanding of the relevance and prognostic implications of specific BCC colonisation is needed. Despite the significant risk posed by *Burkholderia* species in the CF population, evidence for eradication protocols and recommended antibiotic regimens is lacking, which is concerning as it possibly has the most significant effect upon prognosis of all bacterial colonisers [70].
