Multidrug resistant tuberculosis (MDR TB) affects half a million people each year. Levofloxacin is advised for preventive treatment based on observational data, however evidence from large scale clinical trial is unavailable. TB CHAMP and V-QUIN, two phase 3 clinical trials have evaluated safety and efficacy of levofloxacin in preventing MDR TB in participants with household exposure to multidrug resistant M. tuberculosis. Levofloxacin was found to reduce the incidence of multidrug-resistance tuberculosis in both the studies but the reduction in incidence was not significant. A meta-analysis of the data from the TB CHAMP and V-QUIN trials has revealed that levofloxacin was associated with a 60% relative reduction in occurrence of tuberculosis in household MDR-TB contacts.
Mycobacterium tuberculosis resistant to isoniazid and rifampin affects nearly half a million people each year worldwide. It is responsible for multidrug-resistant (MDR) tuberculosis which challenges tuberculosis control programmes. Particularly, young children with household exposure to multidrug-resistant (MDR) tuberculosis runs higher risk of disease. About 2 million children under the age of 15 years are infected with MDR M. tuberculosis.
Levofloxacin, a third-generation fluoroquinolone antibiotic taken orally, which is part of standard treatment for rifampicin-resistant or MDR tuberculosis is advised based on observational data for preventive treatment following exposure to multidrug-resistant (MDR) tuberculosis, however evidence from large scale trials on its efficacy was unavailable.
Two large-scale phase 3 clinical trials – TB CHAMP and V-QUIN have investigated safety and efficacy of levofloxacin in preventive treatment of MDR TB after exposure to multidrug-resistant disease. The findings and conclusions of the two studies were published on 18 December 2024.
The TB CHAMP (Tuberculosis Child Multidrug-Resistant Preventive Therapy Trial) evaluated the efficacy and safety of preventive treatment with levofloxacin in children and adolescents with household exposure to multidrug-resistant tuberculosis. It was conducted on 922 children and adolescents with household exposure to multidrug-resistant tuberculosis during preceding 6 months (but with no evidence of tuberculosis) from 497 households at multiple sites in South Africa. The participants received levofloxacin or placebo daily for 24 weeks. 453 participants received levofloxacin and the rest 469 were given placebo. By week 48, tuberculosis developed in 5 participants (1.1%) in the levofloxacin group and in 12 participants (2.6%) in the placebo group. Thus, the preventive treatment with levofloxacin reduced the incidence of tuberculosis among the children and adolescents with household exposure to MDR TB but the reduction in incidence was not significantly lower than placebo.
The other study (called V-QUIN trial) assessed the efficacy and safety of a 6-month regimen of levofloxacin for the prevention of active tuberculosis among household contacts of persons with confirmed rifampicin resistant or multidrug-resistant (MDR) tuberculosis. This trial was conducted at multiple sites in Vietnam on 2041 participants who were household contacts of persons with rifampicin resistant or MDR tuberculosis. The participants had M. tuberculosis infection but no active disease and had started treatment within the previous 3 months. The participants were randomly assigned to receive 6 months of daily levofloxacin or placebo. 1023 participants received levofloxacin while 1018 Participants placebo. At 30 months, 6 participants (0.6%) in the levofloxacin group were bacteriologically confirmed to have developed tuberculosis while 11 participants (1.1%) in the placebo group were bacteriologically confirmed to have developed tuberculosis. Further, 1participant in the levofloxacin group and 2 in the placebo group were clinically diagnosed with tuberculosis. Thus, the incidence of disease was lower for levofloxacin group than for placebo, but the difference was insignificant.
Both the above-mentioned large-scale phase 3 trials investigated efficacy and safety of levofloxacin in preventing disease among participants with household exposure to multidrug-resistant tuberculosis. In the TB CHAMP, the participants had no evidence of tuberculosis, while in the V-QUIN trial, the participants had M. tuberculosis infection but no active disease. In both the scenarios, levofloxacin was found to reduce incidence of disease, but the reduction was insignificant.
However, a meta-analysis of the data from the TB CHAMP and V-QUIN trials has revealed that levofloxacin was associated with a 60% relative reduction in occurrence of tuberculosis in household MDR-TB contacts.
In September 2024, the WHO had recommended levofloxacin for MDR-TB preventive treatment based on a review of this trial evidence.
Delamanid is currently being evaluated in a clinical trial for preventive treatment of MDR TB. It is an antimicrobial agent that inhibits mycobacterial cell wall synthesis and is approved for treatment of multidrug resistant tuberculosis.
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References:
- Hesseling A.C. et al 2024. Levofloxacin Preventive Treatment in Children Exposed to MDR Tuberculosis. Published 18 December 2024. N Engl J Med 2024;391:2315-2326. Vol. 391 No. 24. https://www.nejm.org/doi/full/10.1056/NEJMoa2314318
- Fox G.J., et al 2024. Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam. Published 18 December 2024. N Engl J Med 2024; 391: 2304-2314. Vol. 391 No. 24. DOI: https://www.nejm.org/doi/full/10.1056/NEJMoa2314325
- Duong T., et al 2024. A Meta-Analysis of Levofloxacin for Contacts of Multidrug-Resistant Tuberculosis. Published 18 December 2024. NEJM Evidence. DOI: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2400190
- Dorman S.E. 2024. Levofloxacin Preventive Therapy for Persons Exposed to MDR Tuberculosis. Published 18 December 2024. N Engl J Med 2024; 391:2376-2378. Vol. 391 No. 24. https://www.nejm.org/doi/full/10.1056/NEJMe2413531
- MRC-UCL. TB-CHAMP trial finds first-ever safe and effective treatment to prevent multidrug-resistant TB in children. 19 December 2024. Available at https://www.mrcctu.ucl.ac.uk/news/news-stories/2024/december/tb-champ-trial-finds-first-ever-safe-and-effective-treatment-to-prevent-multidrug-resistant-tb-in-children/
- WHO. Summary of TB CHAMP and V-QUIN clinical trials. https://tbksp.who.int/en/node/2745
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