Real-world experience of adverse reactions-necessitated rifampicin-sparing treatment for drug-susceptible pulmonary tuberculosis

Abstract

Rifampicin is an important agent for tuberculosis treatment; however, it is often discontinued because of adverse reactions. The treatment regimen then can be administered as that for rifampicin-resistant tuberculosis, which can be toxic. We retrospectively reviewed 114 patients with drug-susceptible pulmonary tuberculosis who discontinued rifampicin due to adverse reactions during an 18 year period at a tertiary referral center, of which 92 (80.7%) exhibited favorable response. Hepatotoxicity was the leading cause of intolerance. Patients with a favorable response were younger and less likely to have comorbidities. The majority of patients were administered four medications during the intensive phase and three to four during the consolidative phase. For those with a favorable response, the median duration of treatment was 10.2 months and the most common intensive regimen was a combination of isoniazid, ethambutol, pyrazinamide, and fluoroquinolone (25%). The most common consolidation regimen was a combination of isoniazid, ethambutol, and fluoroquinolone (22.8%). Among the patients with a favorable response, two (2.2%) experienced recurrence after a follow-up of 3.4 (interquartile range 1.8-6.8) years. For patients with drug-susceptible pulmonary tuberculosis who do not tolerate rifampicin owing to its toxicity, a shorter regimen may be a useful alternative.

Figure 1

Flowchart of the patient selection process. ^aBecause some patients cannot expectorate further sputum after treatment, those who achieved clinical improvement and completed treatment according to the attending physician were included in the favorable response group. ^bIncludes patients who cannot continue treatment owing to underlying conditions (n = 9) and those who are lost to follow-up (n = 3). ^cThe duration of follow-up was a median of 3.4 (interquartile range 1.8–6.8) years. Abbreviation: MDR, multidrug-resistant.

Figure 2

Duration of use of each anti-tuberculosis medication for the 92 patients with favorable outcomes. Box and whisker plots of 92 patients who show a favorable response upon initial treatment. The central line in each box represents the median. The box indicates the 25th and 7th percentiles, and whiskers indicate the range of the data. Gray dots indicate data for each patient. Abbreviations: PAS, p-aminosalicylic acid.

Figure 3

Duration of treatment and follow-ups after diagnosis of pulmonary tuberculosis for the 92 patients with favorable outcomes. The dark gray shade refers to the duration of treatment for pulmonary tuberculosis, whereas the light gray shade refers to the duration of the follow-up. The median duration of follow-up after treatment completion is 3.4 (interquartile range 1.8–6.8) years. Abbreviations: Tb, tuberculosis.