Levofloxacin Lowers Tuberculosis Incidence in Trial, But Results Not Statistically Significant: Study

Prevention of drug-resistant tuberculosis remains a global health priority, yet there is a lack of trials evaluating the effectiveness of treating Mycobacterium tuberculosis infection in contact with individuals with MDR-TB. Levofloxacin, a broad-spectrum antibiotic commonly used for various bacterial infections, has not been extensively studied for its potential in preventing MDR-TB, despite its widespread use in treating other types of infections.

This gap in research prompted Greg J. Fox, Faculty of Medicine and Health, University of Sydney, Medical Foundation Bldg. K25A, Camperdown, Australia, and colleagues to investigate whether levofloxacin could play a role in preventing TB transmission, especially among those at high risk of contracting drug-resistant strains.

For this purpose, the researchers conducted a double-blind, randomized, controlled trial to compare 6 months of daily levofloxacin (weight-based doses) with a placebo for treating M. tuberculosis infection. The trial included household contacts of individuals with bacteriologically confirmed rifampicin-resistant or multidrug-resistant (MDR) tuberculosis in Vietnam. Eligible participants were of any age and had either a positive tuberculin skin test or immunologic impairment.

The primary endpoint was the occurrence of bacteriologically confirmed tuberculosis within 30 months, while secondary endpoints included grade 3 or 4 adverse events, death from any cause, and the development of acquired drug resistance.

The following were the key findings of the study:

• 3948 individuals were screened for eligibility, with 61 (1.5%) having coprevalent tuberculosis and 2041 proceeding to randomization.
• Of the 2041 participants, 97.7% completed 30 months of follow-up, had a primary endpoint event or died.
• Confirmed tuberculosis occurred in 0.6% of participants in the levofloxacin group and 1.1% in the placebo group, with an incidence rate ratio of 0.55, but the difference was not significant.
• Grade 3 or 4 adverse events were similar between the two groups, with a risk difference of 1.0 percentage points.
• Adverse events of any grade were in 31.9% of participants in the levofloxacin group and 13.0% in the placebo group, with a risk difference of 18.9 percentage points.
• There was no acquired fluoroquinolone resistance.

The researchers concluded that, although the incidence of tuberculosis was lower in participants receiving levofloxacin for treating M. tuberculosis infection than those on placebo, the difference was not statistically significant. Levofloxacin was not linked to a notably higher incidence of grade 3 or 4 adverse events, though lower-grade adverse events were more frequently reported in the levofloxacin group.

The researchers suggested that these findings should be considered alongside data from other settings to gain further insights into the potential role of levofloxacin in tuberculosis prevention.

Reference:

Fox GJ, Nhung NV, Cam Binh N, Hoa NB, Garden FL, Benedetti A, Ngoc Yen P, Cuong NK, MacLean EL, Yapa HM, Dowdy DW, Lan NH, Guevara-Rattray E, Duc Cuong P, Solomon O, Behr MA, Marais BJ, Graham SM, Menzies D, Thu Anh N, Marks GB. Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam. N Engl J Med. 2024 Dec 19;391(24):2304-2314. doi: 10.1056/NEJMoa2314325. PMID: 39693541.