Outcome of Burkholderia cepacia colonisation in an adult cystic fibrosis centre

Abstract

Background: Colonisation with Burkholderia cepacia is a poor prognostic indicator in subjects with cystic fibrosis (CF), but outcome prediction is impossible since patients are colonised by different strains with differing pathogenicity. The clinical course of a large cohort of CF patients colonised with UK epidemic (ET12) B cepacia was followed for 5 years and compared with that of the remaining patients in the clinic. Methods: Pulmonary function, nutritional state, and lung pathogen colonisation were recorded for 5 years before December 1997 or death for all 107 patients who had attended the Liverpool adult CF clinic since 1993. For each patient a time line from study entry to date of death or 1997 was constructed. In 1993 potential risk factors including age and sex were subjected to Cox proportional hazards analysis using the end point of mortality as the outcome variable. The analysis was supplemented by time varying covariables that described the change in FEV 1 , BMI, and colonisation status across time, and the excess risk associated with B cepacia colonisation was calculated. Subsequently, in those patients who died between 1993 and 1997, predictive factors for death were compared within groups using complete 5 year data. Results: Thirty seven patients had been colonised by epidemic B cepacia and these patients had four times the mortality of the remainder (p<0.01). In 1993 univariate predictors of mortality were age (alive 19.6 (0.64) v dead 23.8 (1.44); p<0.005) and baseline FEV 1 (alive 68.6 (2.5)% predicted v dead 43.2 (4.8)%; p<0.001) with a trend for BMI (p=0.07). However, following time varying covariate Cox proportional hazards analysis, only lower FEV 1 (hazards ratio 1.1, 95% confidence limits 1.06 to 1.14; p<0.001) and colonisation with B cepacia (hazards ratio 7.92, confidence limits 2.65 to 23.69; p<0.001) were identified as significant factors for death. Surviving B cepacia patients had similar initial lung function to the remaining surviving patients but had an accelerated loss of lung function over the study period (colonised -1.9% predicted per year v non-colonised -0.3% predicted per year; p<0.05). Deceased patients colonised with B cepacia had better spirometric results than the remaining deceased patients 5 years before death (p<0.05) but lost lung function at a greater rate than non-colonised patients (colonised -6.2% predicted per year v non-colonised -1.9% predicted per year; p<0.05). Conclusions: This study confirms the excess mortality associated with epidemic B cepacia colonisation and shows that those with poor spirometric values are at the greatest risk.

Regulation and Functional Significance of Autophagy in Respiratory Cell Biology and Disease

“…B. cepacia is a common pathogen in patients with CF (56), and previous studies have shown that intracellular persistence of the organism in CF macrophages is responsible for the infectious burden (57). In this study, the authors found that B. cepacia infection resulted in down-regulation of several autophagy genes in WT and DF508 macrophages, including Atg5, Atg12, and Atg8 (LC3B), with a more pronounced effect in the latter.…”

Assessing Differences in Mortality Rates and Risk Factors Between Hispanic and Non-Hispanic Patients With Cystic Fibrosis in California

“…Clinical and biologic factors assessed included age and year of diagnosis, 18 sex, 19,20 CF transmembrane conductance regulator (CFTR) genotype, 19,21 infections with Pseudomonas aeruginosa or Burkholderia cepacia, 22,23 and CF-related diabetes (CFRD). 24 CFTR genotype severity was categorized into one of five functional classes proposed by Welsh et al 25 The mutations were further classified into three groups: "high" or "low" disease risk according to the scheme proposed by McKone et al 21 and "unclassified" disease risk for mutations with unknown functional class.…”

“…Infection with P aeruginosa or B cepacia was characterized as dichotomous (never/ever) and by age at first acquisition; earlier age at acquisition is associated with worse prognosis. 23,26,27 Diagnosis of CFRD was characterized as dichotomous (never/ever) and age at diagnosis. 24 Social factors assessed included public insurance status, median household income, 8,19 and access to subspecialty care.…”

Comparative Assessment of Genotyping Methods for Epidemiologic Study of Burkholderia cepacia Genomovar III

“…Recent work has demonstrated that the majority of infected CF patients harbor either B. cepacia genomovar III or Burkholderia multivorans (genomovar II) (1,25,38). Furthermore, limited data suggest that B. cepacia genomovar III (or perhaps certain specific strains within genomovar III) may be relatively more virulent than other species in this complex (3,12,19).The broad-spectrum antimicrobial resistance, absence of a vaccine, and virulence of certain strains have made prevention of B. cepacia complex infection an important goal in CF patient care (21, 22). However, much still remains unknown regarding the epidemiology of infection in CF.…”