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Factors Predictive of Early Discontinuation of Preventive Treatment in Children With Household Exposure to Multidrug-resistant Tuberculosis

2025/07/18 by Trinh Duong, Joanna Brigden, Susan E. Purchase +10 · 1 voice
Medicine · Immunology and Microbiology · #Tuberculosis Research and Epidemiology #Pharmaceutical studies and practices #Antibiotic Use and Resistance

paper · doi:10.1093/ofid/ofaf425

openalex publication_date 2025/07/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

Abstract Background The World Health Organization recommended levofloxacin for tuberculosis (TB) preventive treatment for child and adult contacts of multidrug-resistant TB. Method TB-CHAMP (ISRCTN92634082) was a double-blind community-based multisite randomized placebo-controlled trial assessing levofloxacin as preventive treatment in children with household exposure to adults with microbiologically confirmed multidrug-resistant TB in South Africa. Households were randomized 1:1 to 24 weeks of daily levofloxacin (adult scored 250-mg tablets) versus placebo. Treatment adherence was ascertained through pill counts and treatment cards. Competing risk methods were used to assess factors associated with early treatment discontinuation for nonclinical reasons before achieving ≥80% of allocated doses (adequate treatment). Results Among 911 of 922 children included in analysis, 90% were younger than 5 years of age. Overall, 765 (84%) of children achieved adequate treatment, 135 (15%) discontinued treatment early, and 11 (1%) had not achieved adequate treatment by the end-of-treatment period. Sixty-four (7%) children stopped for clinical reasons and 71 (8%) for nonclinical reasons, with similar proportions across treatment groups. Baseline factors associated with early treatment discontinuation for nonclinical reasons were previous receipt of herbal/traditional medicine (subhazard ratio 3.08; 95% confidence interval, 1.69–5.59; P < .001), and caregivers reporting difficulties administering medication (subhazard ratio 2.73; 1.11–6.71; P = .029). Children with poor treatment adherence by week 4 were more likely to subsequently stop treatment early for nonclinical reasons (subhazard ratio 2.72; 1.06–6.97; P = .037). Conclusions Adherence to the 250-mg levofloxacin formulation was good among young children on preventive TB therapy. Adherence support for children and caregivers, and addressing early signs of poor adherence, may enhance treatment completion.

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