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

Abstract

Background: 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.

Research question: 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?

Study design and methods: 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 6 months 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.

Results: 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 6 months, 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 12 months, 12-month culture conversion was also associated with reduced death (adjusted HR, 0.51; 95% CI, 0.33-0.78).

Interpretation: 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.

Keywords: Mycobacterium abscessus; Mycobacterium avium complex; nontuberculous mycobacteria; treatment.