Time to Positive Culture Detection Predicts Mycobacterium avium Pulmonary Disease Severity and Treatment Initiation

RATIONALE Additional biomarkers are needed to guide initiation of treatment for Mycobacterium avium pulmonary disease (Mav-PD). Time to positive sputum culture detection (TTP) may offer potential prognostic and monitoring value. OBJECTIVE To determine whether TTP is associated with infection severity and early treatment response in Mav-PD? METHODS We undertook a retrospective cohort study of patients with ≥2 sputum cultures positive for M. avium, an 'index' sputum M. avium isolate during 2015-2019, a CT scan within 6 months, and no treatment for ≥6 months prior to index sputum. TTP was estimated from the date of laboratory receipt of the specimen to the date of culture positivity confirmation. TTP was tested for association with markers of infection severity (Mav-PD, bronchiectasis, cavitary disease, treatment initiation by 3 and 6 months, AFB smear) and treatment response using Mann-Whitney U, Spearman's Correlation Coefficient, and Wilcoxon signed-rank tests. We explored a threshold TTP that could identify significant M. avium disease. RESULTS We included 125 patients with mean (SD) age 68.5 (12.5) years and 65% fulfilled disease criteria. Median TTP was 12 days (IQR 10-15; range 6-44). TTP and AFB smear grade were negatively correlated (ρ -0.58, p<0.001). TTP was associated with NTM disease (p=0.03), AFB smear positivity (p<0.001), and treatment initiation by three (p=0.01) and six (p=0.03) months. A threshold TTP of ≤10 days was associated with Mav-PD (80.6% vs 58.4%; ð (95%CI) 22.1 (5.6-38.6)%,p=0.02), AFB smear positivity (83.3% vs 20.2%, ð (95%CI) 63.1(48.3-77.9)%, p<0.001), treatment by three (38.9% vs 13.5%; ð (95%CI) 25.4 (8.0-42.8)%, p=0.003) and six (47.2% vs 19.1%; ð (95%CI) 28.1 (9.9-46.4)%,p=0.003) months. After three and six months of treatment, the median (IQR) change in TTP was +8 (1-undefined; p<0.001) and +7 (0-undefined; p=0.001) days respectively. CONCLUSION TTP is associated with bacterial burden and infection severity and increases in response to treatment. A threshold of ≤10 days may be useful in predicting significant Mav-PD. As a readily available biomarker, further exploration of TTP is imperative.