Deriving Dosages for Levofloxacin Tuberculosis Preventive Treatment for Young People Exposed to Rifampicin-Resistant Tuberculosis
Abstract
Background: Tuberculosis (TB) is the leading single bacterial cause of death worldwide. In 2023, approximately 400 000 people developed multidrug- and rifampicin-resistant TB (MDR/RR-TB), which complicates treatment. TB preventive treatment (TPT) is a critical strategy to prevent the progression from TB infection to TB disease among those at risk. In February 2024, based on data from 2 randomized controlled trials, levofloxacin was strongly recommended by the World Health Organization (WHO) as a TPT option in people of all ages exposed to MDR/RR-TB. There are uncertainties about the optimal dosing of levofloxacin in children and adolescents when using dispersible and solid formulations. We used pharmacokinetic modeling and simulations to determine the best dosing strategy in people aged up to 19 years for both formulations of levofloxacin.
Methods: A previously developed population pharmacokinetic model of levofloxacin in children (0.2-16.8 years) was used and applied to new WHO harmonized weight bands. Simulations were conducted using demographic data from countries with the highest incidence of RR- or MDR-TB. Two currently available levofloxacin formulations (100 mg pediatric, dispersible tablets and 250 mg solid tablets) were considered.
Results: A dosing regimen by weight band was developed for levofloxacin when used as TPT in people aged 0-19 years exposed to MDR/RR-TB. Doses correspond to 8-33 mg/kg for the 100 mg dispersible tablets and 10-42 mg/kg for 250 mg solid…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 400 participants or records.
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