Levofloxacin shows limited efficacy in preventing multidrug-resistant tuberculosis

1. In this randomized controlled trial, daily levofloxacin treatment in patients with multidrug-resistant (MDR) or rifampicin-resistant Mycobacterium tuberculosis did not significantly reduce the incidence of tuberculosis.

2. Levofloxacin treatment was not associated with a significantly increased risk of adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Nearly 40% of patients with rifampicin-resistant or MDR tuberculosis are not treated successfully, highlighting the critical need for preventive strategies. Current treatment standards involve using fluoroquinolones for rifampicin-resistant and MDR tuberculosis. It has been proposed that levofloxacin might also prevent active tuberculosis in close contact with patients with Mycobacterium tuberculosis. This study evaluated the efficacy and safety of a six-month regimen of levofloxacin for this purpose. After 30 months, the incidence of bacteriologically and clinically confirmed tuberculosis was lower in the levofloxacin group than in the placebo group; however, this difference remained statistically insignificant. This trend was consistent across subcategories of age, sex, education level, and coexisting conditions. There was no significant difference in the incidence of adverse events between the two groups. Furthermore, among those who did experience adverse events, those in the fluoroquinolone group were not more likely to experience grade 3 or 4 adverse effects. No cases of acquired fluoroquinolone resistance were observed throughout the study. Of importance, the study was limited by its imprecise estimate of effect, as the observed tuberculosis incidence in the control group (1.1%) was lower than the expected 3%. Despite this limitation, the findings underscore the limited efficacy of levofloxacin in preventing tuberculosis, even though it demonstrated an acceptable safety profile.

Click here to read the study in NEJM

Relevant Reading: Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis

In-Depth [randomized controlled trial]: This randomized controlled trial evaluated the efficacy and safety of daily levofloxacin over six months for preventing active tuberculosis infection among close contacts of individuals with rifampicin-resistant or MDR tuberculosis. Participants were eligible if they lived in one of 10 selected Vietnamese provinces, were household contacts of patients with bacteriologically confirmed rifampicin-resistant or MDR tuberculosis who had started treatment within the previous three months, and showed evidence of M. tuberculosis infection without active disease. Exceptions were made for individuals living with HIV or with a BMI less than 16, who were included regardless of evidence of infection. Pregnant participants could be randomized postpartum. After randomization, 1,023 participants were assigned to the levofloxacin group and 1,018 to the placebo group. The primary outcome was bacteriologically confirmed tuberculosis, identified through culture or a WHO-recommended molecular test. During the 30-month follow-up, confirmed tuberculosis occurred in six participants (0.6%) in the levofloxacin group and 11 participants (1.1%) in the placebo group, yielding an incidence rate ratio of 0.55 (95% CI, 0.15 to 2.40), which was not statistically significant. Clinically probable tuberculosis was observed in 1 participant in the levofloxacin group and 2 in the placebo group, resulting in an incidence rate ratio of 0.49 (95% CI, 0.04–5.46). There was no significant difference between the groups in the risk of adverse events (risk difference, -0.7; 95% CI, -3.5 to 2.2) or in grade 3 or 4 adverse events (risk difference, 1.0; 95% CI, -0.3 to 2.4). No deaths during the study were attributed to tuberculosis, and no cases of acquired fluoroquinolone resistance were reported. While levofloxacin demonstrated an acceptable safety profile, this study did not establish its efficacy in preventing MDR tuberculosis among close contacts.

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