Comparison of different regimens with or without fluoroquinolone in isoniazid-resistant tuberculosis: A multicenter cohort study

Abstract

In 2018, the World Health Organization recommended a 6-month four-drug regimen (rifampicin, ethambutol, pyrazinamide, and levofloxacin) for the treatment of isoniazid-monoresistant tuberculosis. However, the regimen had very low certainty. This cohort study assessed the impact of fluoroquinolone use and initial baseline regimen on treatment effectiveness in isoniazid-monoresistant tuberculosis. This multicenter retrospective cohort study included 318 patients with isoniazid-monoresistant tuberculosis notified between 2011 and 2018 in Korea. Baseline regimens were classified into two groups, namely 6–9-month rifampicin, ethambutol, and pyrazinamide (6-9REZ) and a combination regimen of 2-month rifampicin, ethambutol, pyrazinamide and 7–10-month rifampicin and ethambutol (2REZ/7-10RE). Multivariable logistic regression was performed to assess factors associated with positive treatment outcomes. Of 318 enrolled patients, 234 (73.6%) were treated with the 6-9REZ and 103 (32.4%) with additional fluoroquinolone. In a multivariable logistic regression model comparing the 6-9REZ and 2REZ/7-10RE groups, there was no difference in the odds of positive outcomes (adjusted odds ratio = 1.08, 95% confidence interval = 0.65–1.82). Addition use of fluoroquinolone was not associated with positive treatment outcomes in the whole cohort (adjusted odds ratio = 1.41, 95% confidence interval = 0.87–2.27); however, its additional use was beneficial in the 2REZ/7-10RE subgroup (adjusted odds ratio = 3.58, 95% confidence interval = 1.32–9.75). Both initial baseline regimens, 6-9REZ and 2REZ/7-10RE, were similarly effective. Shortening of the pyrazinamide administration duration with additional fluoroquinolone use could be a safe alternative for patients with potential hepatotoxicity related to pyrazinamide.

Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China

“…On the contrary, a retrospective cohort study conducted in Europe presented no significant difference in the odds of an overall negative outcome between regimens with and without fluoroquinolone [21]. Another multicenter cohort study conducted in Korea compared two regimens, 6-9REZ and 2REZ/7-10RE; they also suggested that the additional use of fluoroquinolone was not associated with favorable outcomes in the whole cohort but benefited the 2REZ/7-10RE subgroup due to a shortened pyrazinamide administration [22]. There were only 20 cases treated with a regimen that included FQ in our study, and the FQ subgroup showed a faint advantage in positive treatment outcomes (p = 0.22).…”

Delphi Survey on the Current and Future Korean Guidelines for Isoniazid-Monoresistant Tuberculosis

“… 21 Another retrospective multicenter cohort study of 318 notified HR-TB case in Korea revealed that shortening duration of PZA administration with additional FQ could be a safe alternative for patients with potential hepatotoxicity related PZA. 22 In certain circumstances, particularly when PZA-related side effects are a concern, this alternative short-course PZA regimen may be a suitable option. ( Table 4 .…”