Density fluctuations of Burkholderia and Achromobacter in cystic fibrosis sputum.

Change in sputum bacterial density has been used to measure efficacy in clinical trials of novel therapies for cystic fibrosis (CF); however, the baseline degree of day-to-day bacterial density change is not well understood. Recent data show that Pseudomonas density in CF sputum has the potential to vary considerably day-to-day even in the absence of antimicrobial treatment. Here we report daily variability of Burkholderia and Achromobacter density in 288 pairs of sputum samples obtained from eight adults with CF. Compared to similar previous analyses of Pseudomonas density, overall variability of day-to-day change for both Burkholderia and Achromobacter was relatively modest (SD=0.54 and 0.58 log10 16S rRNA gene copies/mL, respectively). Significant inter-person variability was observed among the Burkholderia cohort but not among the Achromobacter cohort (P = 0.001 and P = 0.07, respectively). Density changes for both Burkholderia and Achromobacter were inversely correlated with starting densities. This study provides context for the use of changes in sputum bacterial density as a response biomarker in clinical trials of CF therapeutics.