Sydney researchers have discovered that Levofloxacin significantly lowers the chances of contracting drug-resistant tuberculosis. This finding brings new optimism against a disease that affects over 400,000 individuals each year.
A clinical trial reported in the New England Journal of Medicine revealed that taking the oral antibiotic levofloxacin once a day for six months greatly decreased the risk of developing drug-resistant tuberculosis (TB) and nearly halved the risk for both adults and children of developing multidrug-resistant TB.
“Multidrug-resistant TB is a significant global health challenge, impacting more than 400,000 individuals yearly. It leads to considerably worse health outcomes compared to drug-susceptible TB,” explained Professor Gregory Fox, Director of the NHMRC Centre for Research Excellence in Tuberculosis, who led the VQUIN trial at the Woolcock Institute of Medical Research at the University of Sydney, in partnership with the Vietnam Tuberculosis Program.
“We have now discovered a method to prevent individuals with early TB infection from becoming ill and transmitting the infection to others.”
The trial involved 2,041 family members of individuals with drug-resistant TB, all of whom had early-stage infections that had not yet progressed to the active state of drug-resistant TB. The research was conducted across ten provinces in Vietnam, a country with a notably high incidence of drug-resistant TB.
The trial established that levofloxacin decreased the risk of multidrug-resistant tuberculosis (MDR-TB) in adults and teens by 45 percent. The results of this trial were combined with a second trial, TB-CHAMP, conducted in South Africa, which included the same treatment for children. Together, the findings from both studies illustrated that levofloxacin could mitigate the risk of MDR-TB among family members and other household contacts, helping to lessen the global impact of this serious pathogen. The combined results were published simultaneously in the partner journal NEJM Evidence.
Up to now, there has been limited information available on preventive treatments for MDR-TB, as no randomized controlled trials had been undertaken before.
“The VQUIN trial represents a significant advancement in the battle against drug-resistant TB. This evidence transforms how we manage individuals at risk of drug-resistant TB in Australia and worldwide. The advantages for families and communities vulnerable to MDR TB are considerable,” remarked Professor Fox, who is also a research leader at the Woolcock Institute of Medical Research.
“MDR-TB is one of the toughest diseases to treat, and children have traditionally been the most overlooked patients,” stated Professor Ben Marais, a Chief Investigator from VQUIN TB-CHAMP from the University of Sydney. “By discovering a way to safeguard at-risk family members, we assist the entire family in overcoming the effects of MDR-TB. This yields not only health benefits but also economic and mental well-being advantages.”
During the trial, the 2,041 adults and children living with a person diagnosed with MDR-TB were given a regimen of levofloxacin for six months and monitored for a duration of 30 months. The findings indicated a 45 percent reduction in TB cases among the group that received levofloxacin compared to those who received a placebo. Interestingly, the placebo group exhibited fewer TB cases than expected. Overall, levofloxacin was proven to be safe and well-tolerated among both adults and children.
TB remains one of the leading causes of death in children worldwide and ranks as one of the top threats to children under five. Each year, an estimated 400,000 people contract MDR-TB disease, which is complicated to treat with existing medications, known to produce multiple side effects. The treatment can be very expensive for both families and healthcare services.
In September 2024, the World Health Organization released new guidelines for MDR-TB preventive treatment, which were informed by the results of the VQUIN trial.
The trial also examined other vital factors, including the acceptability of the treatment regimen, feasibility, health economics, pharmacokinetics, and antimicrobial resistance.
The teams from the VQUIN trial in Australia and the TB CHAMP trial in South Africa worked together prior to unveiling the trial results. They merged their data on efficacy and safety using both traditional and innovative Bayesian methods. Collectively, they evidenced that across both trials, levofloxacin lowered the risk of developing TB by 60 percent. Innovative Bayesian analysis indicated comparable results for each trial separately.
