Patients who have drug-resistant tuberculosis (TB) have a similar microbiological response to bedaquiline-based second-line medications as patients with drug-sensitive TB taking first-line regimens, according to researchers at Weill Cornell Medicine in New York and GHESKIO Centers in Haiti.
Second-line medications are those that are given when one or more of the drugs given first for the disease are not effective. The research could have implications for shortening the duration of treatment for drug-resistant TB, which currently requires medications for up to 2 years, while those with drug-sensitive TB complete treatment in about 6 months.
The study, published in The Journal of Infectious Diseases, “is thought to be the first to address the knowledge gap surrounding the microbiological response of patients receiving these two therapies,” said the paper's lead author Dr. Kayvan Zainabadi, assistant professor of molecular microbiology at Weill Cornell Medicine.
“We found that the new drugs we use to treat the drug-resistant form of the disease are as effective as our first-line medicines,” said study co-author Dr. Daniel W. Fitzgerald, director of the Center for Global Health at Weill Cornell Medicine. “Historically, they were much worse.”
Evolving treatments for a devastating disease
Mycobacterium tuberculosis, the bacterium that causes TB, infects the lungs, causing cough, fever, and often death. Worldwide, 10.6 million people developed the condition in 2022, resulting in about 1.3 million deaths, according to the World Health Organization (WHO), making it the top infectious disease killer worldwide. Approximately four percent of new TB infections are drug-resistant, which disproportionately contributes to 12 percent of deaths from the disease.
In 2012, the United States Food and Drug Administration approved bedaquiline, the first new TB drug in four decades, leading the WHO to update treatment guidelines for drug-resistant TB in 2018. The new guidelines allowed for bedaquiline, an oral drug, to replace the more toxic injectable antibiotics such as streptomycin. These new regimens are also much easier to implement in the resource-limited settings where TB is common.
Together, these factors improve the chances of patients completing treatment, which is important because not doing so results in more drug resistance, Dr. Zainabadi said.
Due to differing drug availabilities across the world, there is no single standard bedaquiline-based second-line regimen for drug-resistant TB. Rather, the WHO recommends using a combination therapy consisting of different classes of antibiotics based on availability and local drug resistance patterns. How these new oral, bedaquiline-based second-line treatments compare to first-line therapies in their ability to kill the bacteria is not well understood and prompted the research team to conduct their research.
For this study, the researchers assessed 31 subjects with drug-sensitive TB who took first-line treatment (rifampin, isoniazid, ethambutol, and pyrazinamide) and 23 subjects with drug-resistant TB who took second-line treatment (bedaquiline, pyrazinamide, levofloxacin, linezolid, and clofazimine). Patients were enrolled through Weill Cornell Medicine's partner in Haiti, the Haitian Study Group on Opportunistic Infections and Kaposi's Sarcoma, or GHESKIO.
Source: Weill Cornell Medical College