Upping tuberculosis drug dose defeats disease faster

Increasing Rifampicin dosage shortens treatment period without side effects

Increasing the daily dosage of a key tuberculosis antibiotic can contain the disease better and does not have any side effects.

Higher daily doses of rifampin, a cornerstone of tuberculosis treatment, killed more TB bacteria in sputum cultures.

The findings of the randomized controlled trial that proved this, were published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

In “Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis: A Randomized Controlled Trial,” Gustavo E. Velásquez, MD, MPH, associate physician in the Division of Infectious Diseases at Brigham and Women’s Hospital in Boston, and co-authors report on a phase 2 trial conducted in Lima, Peru. The trial involved 180 adults with new, drug-susceptible TB.

The trial found that each five mg/kg/day increase in rifampin increased the elimination rate of TB bacteria from sputum

India has the largest number of TB patients in the world. According to the Global TB report 2017, the total burden of TB in India is estimated to be 28,00,000, a quarter of the world’s TB cases.

Previous studies had looked at whether intermittent delivery of higher doses of rifampin were effective in killing the TB bacterium. They found that intermittent higher doses were more toxic than lower doses.

The authors of the current trial said that the findings were particularly encouraging because they suggest that at a high enough dose of daily rifampin, a treatment period of less than the standard six months may be possible.

“Six months of treatment with four drugs–often delivered with support and supervision–represents a substantial burden on the health care system, as well as on the patient,” Dr. Velásquez said. “Patients who cannot complete the full regimen may not be cured, which permits ongoing transmission and the development of drug-resistant TB.”

The authors wrote that optimization of rifampin dosing is a priority because it has the most potent sterilizing effect of the four first-line agents, is available throughout the world, and costs only pennies per capsule.

The trial found that each five mg/kg/day increase in rifampin increased the elimination rate of TB bacteria from sputum.