Antibiotic treatment for drug-resistant tuberculosis found to be safe and effective in clinical trial

A clinical trial published in the New England Journal of Medicine showed that the oral antibiotic levofloxacin taken once-daily for six months substantially reduced the risk of developing drug-resistant tuberculosis (TB), and almost halved adults’ and children’s risk of developing multidrug-resistant TB.

“Multidrug-resistant TB is a major global public health problem, affecting over 400,000 people each year. It is associated with significantly poorer outcomes than drug-susceptible TB,” said Professor Gregory Fox, Director of the NHMRC Centre for Research Excellence in Tuberculosis who led the VQUIN trial at the University of Sydney’s Woolcock Institute of Medical Research in collaboration with the Vietnam Tuberculosis Program.  

“We now have a way of stopping people with early TB infection from becoming sick and spreading their infection to other people.”

The trial enrolled 2,041 family members of people with drug-resistant TB. These family members had early infection, which had not yet developed into the active form of drug-resistant TB. The study was conducted across 10 provinces in Vietnam, a country with a high rate of drug-resistant TB.

The trial found that levofloxacin reduced the risk of multidrug-resistant tuberculosis (MDR-TB) in adults and adolescents by 45 percent. The trial findings were combined with a second trial, TB-CHAMP, that took place in South Africa and involved the same treatment in children. Together, the two studies demonstrated that levofloxacin could stop the risk of MDR-TB among family and other household members, curtailing the global impact of this dangerous pathogen. The combined analysis was published on the same day in the companion journal NEJM Evidence.

Evidence to date has been limited on MDR-TB preventive treatment since no randomised controlled trials had ever been conducted.

“The VQUIN trial is a major step forward in the fight against drug-resistant TB. “This evidence changes the way we care for people at risk of drug-resistant TB in Australia and globally. The benefits to the families and communities at risk of MDR TB is substantial,” said Professor Fox, who is also research leader at the Woolcock Institute of Medical Research.

“MDR-TB is one of the most challenging diseases to cure, and children have always been the most neglected patients,” said Professor Ben Marais, a Chief Investigator from VQUIN TB-CHAMP from the University of Sydney. “By finding a way to protect vulnerable family members, we help the whole family recover from the effects of MDR-TB. There are not just health benefits, but also economic and mental health benefits.”

In the trial, 2,041 adults and children living with a person with MDR-TB in the household were given six months of levofloxacin and monitored for 30 months. The study found that there were 45 percent fewer cases of TB in the group given levofloxacin compared to the placebo group. A lower number of cases of TB occurred in the placebo group than expected. Overall, levofloxacin was found to be safe and well-tolerated in adults and children.

TB remains one of the top causes of death in children globally and is one of the top killers of children below five years of age. An estimated 400,000 people develop MDR-TB disease each year, which is complex to treat with current medications that have many side effects. The treatment is very costly for both families and health services.

In September 2024, the World Health Organisation issued new guidelines for MDR-TB preventive therapy. The guidelines were based on the findings of the VQUIN trial.

The trial also completed work on other important considerations such as acceptability of the drug regimen, feasibility, health economics, pharmacokinetics and antimicrobial resistance.

The teams from the VQUIN trial in Australia and TB CHAMP trial in South Africa collaborated before the trials were unblinded. They combined their data on efficacy and safety in traditional and novel Bayesian approaches. Jointly, they showed that across both trials, levofloxacin reduced the risk of developing TB by 60 percent. Novel Bayesian analysis showed similar results for each trial, individually.