Levofloxacin does not prevent infection in children exposed to MDR tuberculosis

1. In this randomized controlled trial, among children and adolescents with household exposure to an adult with multidrug-resistant tuberculosis, it was found that levofloxacin did not result in a significantly lower incidence of infection compared with placebo.

2. Preventive treatment with levofloxacin was not associated with any safety concerns, with the levofloxacin and placebo groups having similarly low proportions of participants with serious adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Each year, approximately half a million people worldwide develop tuberculosis. Current approaches to controlling MDR tuberculosis primarily focus on diagnosing the disease in symptomatic persons and initiating effective treatment, but studies suggest that contact management and delivery of preventive treatment to healthy persons at high risk for disease progression would be more effective. Young children, particularly those under five years of age, are an important population for tuberculosis preventive treatment, as they are at higher risk of faster disease progression and more severe forms of tuberculosis following exposure. Observational data suggest that tuberculosis preventive treatment regimens containing fluoroquinolones are associated with a low risk of tuberculosis. The present trial assessed the efficacy and safety of levofloxacin compared with placebo for tuberculosis prevention among children and adolescents with household exposure to an adult with MDR tuberculosis. Tuberculosis did occur in a smaller percentage of participants in the levofloxacin group compared with the placebo group, but this difference was not significant. Regarding safety, the proportion of participants with serious adverse events was similar between the two groups. The study was limited in its generalizability, with over 90% of participants being under five years of age; as such, the findings may not apply to older children and adolescents, who may have more non-household exposure to tuberculosis. Nevertheless, these findings demonstrate that levofloxacin does not effectively prevent tuberculosis in children with household exposure to an adult with MDR tuberculosis.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This double-blind, cluster-randomized trial compared the efficacy of levofloxacin for tuberculosis prevention with that of a placebo among children and adolescents with household exposure to an adult with MDR tuberculosis. Children under five years of age, regardless of interferon-γ release assay result or HIV status, and children 5-17 with a positive interferon-γ release assay or HIV infection who had been exposed to an index patient within the last six months and had no evidence of tuberculosis were eligible. The primary efficacy outcome was the incidence of tuberculosis by week 48. The primary safety outcome was any grade three or higher adverse event related to the trial regimen. A total of 922 participants were included in the study, with 453 assigned to the levofloxacin group and 469 assigned to the placebo group. Incident tuberculosis by week 48 occurred in 1.1% of participants in the levofloxacin group (1.2 cases per 100 person-years; 95% Confidence Interval [CI], 0.5 to 2.9), compared with 2.6% in the placebo group (2.9 cases per 100 person-years; 95% CI, 1.6 to 5.2), yielding a hazard ratio of 0.44 (95% CI, 0.15 to 1.25; P=0.12). By week 72, incident tuberculosis occurred in 1.3% of participants in the levofloxacin group and 2.8% of participants in the placebo group (hazard ratio, 0.49; 95% CI, 0.18 to 1.30). 0.9% of participants in the levofloxacin group had a grade three or higher adverse event related to the trial regimen, compared with 1.7% of participants in the placebo group (hazard ratio, 0.52; 95% CI, 0.16 to 1.71; P=0.29). Two deaths occurred, neither of which was related to the trial regimen or tuberculosis. In both groups, 86% of participants received at least 80% of the assigned doses, and poor adherence was not associated with an increased incidence of tuberculosis. In summary, while tuberculosis occurred in a smaller percentage of participants in the levofloxacin group compared to the placebo group, this difference was not significant.

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.