P3 ECBS study: exacerbation of chronic bronchial sepsis – utility of a novel rapid molecular diagnostic test (MBLA) to detect and quantify viable bacteria

<h3>Introduction and Objectives</h3> The significant overlap of clinical features of patients with bronchiectasis and those with COPD and frequent infections has led to the term ’chronic bronchial sepsis’ (CBS). Culture-dependent techniques lack sensitivity, are time-consuming and rarely helpful in acute exacerbations. We have developed a novel rapid sputum diagnostic test, the molecular bacterial load assay (MBLA), a ribosomal RNA-based qPCR assay able to provide both diagnostic and quantitative data on viable bacteria. After successful lab development, we sought to provide proof-of-concept data for the CBS-MBLA in clinical practice. <h3>Methods</h3> The Exacerbation of CBS (ECBS) study is a prospective observational study of patients with a history of CBS (confirmed bronchiectasis or COPD with positive sputum bacteriology) presenting to hospital with acute severe exacerbation. Sputum was processed alongside standard care. The CBS-MBLA identifies commonly identified bacteria in CBS: <i>P.aeruginosa, H.influenzae, S.pneumoniae, S.aureus, M.catarrhalis, K.pneumoniae</i>. The primary outcome was MBLA performance compared to sputum culture. Secondary outcomes included longitudinal assessment of bacterial loads over time and quality of life (QoL). <h3>Results</h3> 26 patients with 29 exacerbation-admissions were enrolled and tracked over 8-months with the following baseline features: median age 72 (49–89); 1.9 female:1 male; COPD 59%, bronchiectasis 41%; ever-smokers 68%; BMI 21.9kg/m² (13.8–36.7); CAT score 30 (5–40); inhaled steroids 26%; admission blood results CRP 52 g/l (1.6–210.3), neutrophils 8.8 x 10⁹(2.9–20.5). Compared to culture, CBS-MBLA showed higher diagnostic yields from day 1 sputum (14/27 (52%) vs 10/27 (37%)) and when all day 1–3 sputum was included (24/27 (89%) vs 12/29 (41%)). <i>H.influenzae</i> (17) and <i>P.aeruginosa</i> (12) were the most commonly identified bacteria by MBLA. Of 3 negative MBLA results, 1 cultured <i>S.pseudopneumoniae</i> and 2 remained culture-negative. MBLA-bacterial loads did not consistently fall during clinical recovery, either between different patient-pathways or within the same patient (figure 1). High QoL scores at presentation reduced significantly with treatment, however, the sample size precluded sufficient correlation with MBLA values. <h3>Conclusions</h3> We have shown proof-of-concept of the CBS-MBLA in clinical practice in acute exacerbations. We show 89% sensitivity despite antibiotic use and consistent performance on quantitative viable bacterial loads. CBS-MBLA offers significant potential value in clinical practice and in our understanding of CBS.