Systemic quorum sensing signal molecules are biomarkers for current and future P. aeruginosa infection in cystic fibrosis patients: A longitudinal study

Rationale: Early diagnosis of pulmonary Pseudomonas aeruginosa in cystic fibrosis (CF) is necessary to permit timely eradication therapy, but is difficult in those who are unable to expectorate sputum. Specific P. aeruginosa quorum sensing signal molecules (QSSMs) are detectable in the systemic circulation of patients with CF, suggesting they have potential as biomarkers to aid diagnosis of infection. Methods: A prospective multicentre observational study of 176 adults and 68 children with CF. Cross-sectionally, comparisons were made between current infection with P. aeruginosa using QSSMs detected in sputum, plasma and urine, and routine hospital respiratory culture results. In longitudinal analysis, children with CF were reviewed annually for 3 years to determine if QSSMs are potential early biomarkers for future P. aeruginosa . Results: In children, plasma HHQ (2-heptyl-4-hydroxyquinoline) had a sensitivity of 86% and specificity of 86% and, in urine, the sensitivity was 79% and specificity was 71%, compared to conventional microbiological culture. In longitudinal analysis of 45 children without P. aeruginosa infection at baseline, plasma HHQ was significantly associated with subsequent positive culture during the following year (OR=1.04 (95% CI=1.01 to 1.06; p<0.01). Of the children who became P. aeruginosa culture positive in the first year, 71% (5/7) had detectable HHQ in plasma at baseline compared to 3% (1/38) of those who remained culture negative. Conclusions: Systemic QSSMs are sensitive and specific biomarkers for P. aeruginosa in patients with CF and have potential to direct earlier intervention with eradication therapy.