Relationship between Sputum Bacterial Load and Lung Function in Children with Cystic Fibrosis Receiving Tobramycin.

Abstract

Background: Chronic pulmonary infection with pathogens such as Pseudomonas aeruginosa is associated with lung function decline and increased mortality in people with cystic fibrosis (CF). The relationship between sputum bacterial load and the severity of pulmonary exacerbations remains unclear. This study aimed to explore the relationship between sputum bacterial load and clinical response to antibiotic treatment of pulmonary exacerbations in children with CF.

Methods: Multicentre prospective longitudinal study of children with CF receiving IV tobramycin for a pulmonary exacerbation and who had prior isolation of Gram-negative bacteria and able to expectorate sputum. Lung function (FEV₁) and sputum bacterial load were assessed. Bacterial load was performed using quantitative PCR on either intact (live) bacterial cells or all bacterial DNA (live+dead) and targeted either P. aeruginosa only or all bacteria.

Results: Twelve children (14 admissions) were enrolled and each provided ≥2 sputum samples; 11 children (13 admissions) also had ≥2 FEV₁ measurements. In 10 admissions where FEV₁ improved, five showed a reduction in all live bacteria, with a median reduction by 8.65×10⁶ copies/g (73% reduction). Live P. aeruginosa was detected in 8/10 children and in seven, a median reduction of 2.99×10⁷ copies/g (90% reduction) was observed. Improved FEV₁ correlated with greater reductions in live+dead P. aeruginosa (ρ = -0.63, p = 0.04).

Conclusion: A greater reduction in total sputum P. aeruginosa bacterial load (live+dead) was associated with improved lung function (FEV₁) in children with CF receiving tobramycin.