Effect of Intermittency on Treatment Outcomes in Pulmonary Tuberculosis: An Updated Systematic Review and Metaanalysis

Background: Intermittent regimens offer operational advantages in tuberculosis treatment, but their efficacy has been questioned. We updated a systematic review and metaanalysis to examine the efficacy of different intermittent dosing schedules in first-line pulmonary tuberculosis therapy.

Methods: An updated search included randomized control trials (RCTs) that reported on first-line pulmonary tuberculosis therapy between June 2008 and March 2016. We pooled proportions of failure, relapse, and acquired drug resistance (ADR) for 4 dosing schedules: daily throughout, thrice weekly throughout, daily (intensive phase) then thrice weekly (continuation phase), and daily (intensive phase) then twice weekly (continuation phase). Metaregression was performed using a negative binomial regression model.

Results: After screening 5874 citations, 7 RCTs with 10 arms were added for a total of 56 RCTs with 110 arms. The pooled proportion of relapse was significantly higher in arms with thrice weekly therapy throughout (6.8; 95% confidence interval [CI], 3.8-9.9) and twice weekly therapy in the continuation phase (7.3; 95% CI, 3.5-11.1) when compared with daily therapy (2.5; 95% CI, 1.8-3.2; P < .01). Metaregression revealed higher rates of relapse (2.2; 95% CI, 1.2-4.0), failure (3.7; 95% CI, 1.1-12.6), and ADR (10.0; 95% CI, 2.1-46.7) in arms with thrice weekly throughout and higher rates of failure (3.0; 95% CI, 1.0-8.8) with twice weekly in the continuation phase when compared with daily therapy.

Conclusion: Thrice weekly dosing throughout therapy, and twice weekly dosing in the continuation phase appear to have worse microbiological treatment outcomes when compared with daily therapy.