No significant benefit of Levofloxacin in Prevention of MDR Tuberculosis in Children, finds study
Researchers have identified that preventive therapy with levofloxacin led to a reduced incidence of tuberculosis over placebo in children with exposure to multidrug-resistant (MDR) tuberculosis. A recent study was published in The New England Journal of Medicine by Anneke and colleagues.
MDR tuberculosis is an important global health issue, with close to 2 million children aged below 15 years infected across the world and about 30,000 developing MDR tuberculosis each year. This research aimed to bridge the gap by determining if levofloxacin could decrease the occurrence of tuberculosis in exposed children effectively and determining its safety profile.
A total of 922 children from 497 families were enrolled in the study. Children aged below five years were eligible irrespective of their interferon-γ release assay status or HIV infection, whereas children aged 5 to 17 years were eligible if they tested positive for interferon-γ release assay or HIV disease. Families were assigned randomly to receive either levofloxacin or a placebo for 24 weeks, whereas children received once-daily doses of the assigned regimen.
The main efficacy outcome was the occurrence of tuberculosis by week 48, including death due to tuberculosis. The main safety outcome was the development of grade 3 or greater adverse events during treatment that were at least possibly related to the study drug.
Key Findings
• Of the 922 children enrolled, 453 were given levofloxacin and 469 were given placebo. Most (91%) were less than five years old. Adherence to treatment was good, with 86% of participants in both groups receiving 80% or more of the doses assigned.
• Tuberculosis occurred in 5 participants (1.1%) by week 48 in the levofloxacin group and in 12 participants (2.6%) in the placebo group. The hazard ratio (HR) for developing tuberculosis in the levofloxacin group was 0.44 (95% CI, 0.15 to 1.25).
• At least possibly related treatment adverse events of grade 3 or greater occurred in 4 patients in the levofloxacin group and 8 patients in the placebo group (HR, 0.52; 95% CI, 0.16 to 1.71). One child in the levofloxacin group also developed grade 2 tendonitis.
• The findings were consistent across different sensitivity analyses, which supported the primary analysis results.
The study authors indicated that other approaches or further studies might be needed to determine effective preventive interventions for MDR tuberculosis in children.
Reference:
Hesseling, A. C., Purchase, S. E., Martinson, N. A., Fairlie, L., Schaaf, H. S., Brigden, J., Staples, S., Gibb, D. M., Garcia-Prats, A., Conradie, F., McGowan, C., Layton, C., Batist, E., Demers, A.-M., Nyamathe, S., Frigati, L., Turner, R., Duong, T., & Seddon, J. A. (2024). Levofloxacin preventive treatment in children exposed to MDR tuberculosis. The New England Journal of Medicine, 391(24), 2315–2326.https://doi.org/10.1056/nejmoa2314318
