Pulmonary nontuberculous mycobacterial infections: antibiotic treatment and associated costs

Abstract

Recent studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease. In the absence of prevalence and cost data, the public health burden of pulmonary NTM disease is difficult to assess. The goal of this study was to assess costs associated with NTM disease treatment and to identify risk factors associated with increased costs. Records from subjects with pulmonary NTM disease enrolled in a natural history protocol were abstracted for presenting symptoms, comorbidities, microbiology, and treatment histories. Antibiotic frequency, duration, adverse reaction, and costs were noted, the total antibiotic burden and cost were calculated, and risk factors associated with high costs were analyzed. From Jan 2004 to Dec 2005, 33 subjects were enrolled; 27 met disease criteria and had sufficient data to assess antibiotic use. Mycobacterium avium complex was present in 89% and Mycobacterium abscessus was present in 21% of subjects. Subjects received a median of 5 (1-10) antibiotics. Adverse effects were common seen in up to 50% with common antibiotics and up to 100% with uncommonly used antibiotics. Median burden of treatment was 2638 (84-7689) drug-days and the median total cost per patient was $19,876 ($398-70,917). Subjects with high treatment costs had an adjusted 9.5 fold (95% CI 1.5-97.2) likelihood of having M. abscessus and a 4.2 fold (95% CI 0.6-59.3) increased likelihood of having more extensive disease. Pulmonary NTM represent an underappreciated disease burden in the US population, with an associated treatment cost comparable to that for other chronic diseases of infectious origin such as HIV/AIDS.

Figure 1

Figure 1a: CT findings. Normal = no nodular bronchiectasis or cavitary disease; these subjects received on average, 5 months of treatment before enrollment at the NIH. Mild = nodular bronchiectasis limited to less than 3 lobes with no cavitary disease. Moderate = nodular bronchiectasis involving 3 or more lobes and/or cavitary disease limited to one lobe. Severe = multilobar cavitary disease regardless of presence or extent of nodular bronchiectasis. For the purposes of this categorization, the lingula was considered a separate lobe. Figure 1b: Distribution of organism among persons with moderate\severe disease Figure 1c. : Distribution of organism among persons with mild\moderate disease

Figure 1

Figure 1a: CT findings. Normal = no nodular bronchiectasis or cavitary disease; these subjects received on average, 5 months of treatment before enrollment at the NIH. Mild = nodular bronchiectasis limited to less than 3 lobes with no cavitary disease. Moderate = nodular bronchiectasis involving 3 or more lobes and/or cavitary disease limited to one lobe. Severe = multilobar cavitary disease regardless of presence or extent of nodular bronchiectasis. For the purposes of this categorization, the lingula was considered a separate lobe. Figure 1b: Distribution of organism among persons with moderate\severe disease Figure 1c. : Distribution of organism among persons with mild\moderate disease

Figure 1

Figure 1a: CT findings. Normal = no nodular bronchiectasis or cavitary disease; these subjects received on average, 5 months of treatment before enrollment at the NIH. Mild = nodular bronchiectasis limited to less than 3 lobes with no cavitary disease. Moderate = nodular bronchiectasis involving 3 or more lobes and/or cavitary disease limited to one lobe. Severe = multilobar cavitary disease regardless of presence or extent of nodular bronchiectasis. For the purposes of this categorization, the lingula was considered a separate lobe. Figure 1b: Distribution of organism among persons with moderate\severe disease Figure 1c. : Distribution of organism among persons with mild\moderate disease

Figure 2

Burden of treatment and medication costs. Box and whisker plots where the plus signs and horizontal lines within the boxes represent the mean and median values, the top and bottom of boxes represent the 75th and 25^th percentiles, the vertical lines represent the 95^th and 5^th percentiles, and the circles represent outliers. Data are categorized for all subjects, those with Mycobacterium abscessus (MABS), and those with Mycobacterium avium complex (MAC) and represent: a. Total burden of treatment per patient in drug-days (sum of the number of days on each drug); b. Monthly burden of treatment (total burden divided by the number of months of follow-up); c. Total medication costs per patient; d. Monthly medication costs per patient.

Figure 3

Three examples of NTM treatment courses. Frequent interruptions, substitutions, and dosage changes made identification of discrete antibiotic courses difficult.