Impact of Time Between Diagnosis and Treatment for Nontuberculous Mycobacterial Pulmonary Disease on Culture Conversion and All-Cause Mortality

Abstract

Limited data are available regarding when to start treatment after a diagnosis of nontuberculous mycobacteria-pulmonary disease (NTM-PD) or regarding how achieving culture conversion affects NTM-PD outcomes. Does the time between diagnosis and antibiotic initiation influence culture conversion or all-cause mortality in NTM-PD, and is there any association between achieving culture conversion after antibiotics and reduced all-cause mortality? We evaluated 712 patients who received antibiotics for 6 or more months after diagnosis of NTM-PD between July 1997 and December 2013. Data on the waiting period, defined as the interval between diagnosis and treatment initiation, and on outcomes such as culture conversion by 6months or death were collected. Factors associated with outcomes were analyzed after adjusting for disease severity, using the BMI, age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES) system. Thirty-eight percent of study patients had mild disease, 48%had moderate disease, and 14%had severe disease. The median waiting period without antibiotics among all patients was 4.8 (interquartile range, 1.3-20.8) months. After treatment initiation, 479 (67%) patients achieved culture conversion within 6months, and 135 (19%) patients died. In univariable and multivariable models adjusted for BACES severity, no association between the waiting period and 6-month culture conversion or death was identified. However, 6-month culture conversion demonstrated a significant negative correlation with death (crude hazard ratio [HR], 0.46, 95%CI, 0.33-0.65; adjusted HR, 0.51, 95%CI, 0.35-0.74). In the subgroup treated for more than 12months, 12-month culture conversion was also associated with reduced death (adjusted HR, 0.51; 95%CI, 0.33-0.78). It may be reasonable to start antibiotics according to the "watchful waiting" strategy for NTM-PD, but given the survival benefits, achieving culture conversion is an important goal for patients in need of treatment.