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Drug-resistant Tuberculosis Responds Rapidly To Bedaquiline-based Second-line Therapy

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 Dec. 7 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 contribute 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.

The Study Data

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.

The researchers measured the number of bacteria in the patient sputum using an automated clinical test as well as sophisticated laboratory methods capable of detecting cryptic bacteria that typically go undetected by routine methods. They then looked at the rate of the decrease in bacteria over time with therapy.

"The laboratory work to measure the quantity of bacteria in sputum is incredibly laborious and requires bio-safety level 3 facilities, so it's not something you can do on a thousand people," said Dr. Fitzgerald, who is also the B.H. Kean Professor in Tropical Medicine and professor of medicine in microbiology and immunology at Weill Cornell Medicine.

"The rate of decline measured at two weeks was comparable in the two groups by all measures," said study statistician Dr. Myung Hee Lee, associate professor of clinical epidemiology in medicine and associate professor of statistics. Just two months after treatment, 77.8 percent of patients from both groups tested negative for the bacterium.

"Patients who have drug-resistant TB tend to have advanced disease, and most have previously been treated with first-line drugs," Dr. Zainabadi said. "Seeing them respond at the same rate as drug-sensitive patients to treatment is encouraging."

The comparable response observed in the study may mean treatment can be shortened in drug-resistant patients. However, he noted that resistance to one of the other drugs in the regimen, pyrazinamide, was associated with slower killing of the bacterium during the first two weeks of therapy. These patients may need to be monitored and treated for an extended time.

These study results also support two clinical studies from other institutions, not yet published in peer-reviewed journals, that evaluated patient outcomes, Dr. Zainabadi said.

Future Research

The Weill Cornell Medicine researchers want to build on prior studies in Scientific Reports and mBio investigating better tools for monitoring the disease, Dr. Zainabadi said. "What we're really missing is a clinical diagnostic that can accurately monitor how patients are responding to therapy, including how well regimens are killing TB, and when cure is achieved."

The researchers are also conducting studies using the newer drugs, including bedaquiline, as an alternative to the first-line regimen in people with drug-sensitive-TB, said Dr. Fitzgerald. Some patients can't tolerate the first-line treatment or are allergic to some of the drugs, he said.

"Overall research is moving in the direction of finding new drug regimens for TB and shorter and shorter treatments," Dr. Fitzgerald said. "We now have options for patients."

Molecular Insights May Inform New Treatments For Drug-resistant Tuberculosis

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Maine Residents On Alert As World's Deadliest Disease Strikes State: What To Know

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The Maine Center for Disease Control and Prevention (CDC) says tuberculosis (TB) cases are on the rise in the state. Three people in the Greater Portland area, all unrelated, have been infected with the world's deadliest disease.

The three people in the state that were infected got tuberculosis from different sources. Lindsay Hammes, spokesperson for the Maine CDC, said the three active cases are not genetically linked, which means that they were also not transmitted from one person to another.

Health officials currently are trying to identify and screen any people who may have come into contact with the infected individuals. They also stated that rumors of a tuberculosis outbreak at the Portland shelter for asylum seekers are not true.

Statement from the Maine CDC

"As the Maine CDC does for all TB cases, we are doing contact investigations and identifying individuals who may be at highest risk; for those individuals deemed at highest risk, the Maine CDC recommends screening by a medical professional," Hammes told News Center Maine. "Per our protocol, the Maine CDC also notified infection preventionists at hospitals about the potential for people coming to be screened. The Maine CDC's Public Health Nursing team also recently held a TB screening event in Portland."

While there is no current outbreak in the state – the cases in Maine do not meet the criteria needed to classify them as an outbreak, there have been a total of 28 cases of tuberculosis reported in Maine in 2025 through the end of July. In 2024, there were 10,347 reported cases of tuberculosis in the United States. That was the highest number of tuberculosis infections in the country since 2011 when there were 10,471 cases recorded.

Tuberculosis symptoms and treatment

The World Health Organization calls tuberculosis the "world's top infectious killer," causing the deaths of about 1.25 million people every year, the majority occurring in developing countries. This despite the fact that the disease can be prevented by vaccines and treated with antibiotics. The vaccine is not usually given in the U.S. Due to the low likelihood of Americans contracting the disease.

Common symptoms of tuberculosis include a prolonged cough, chest pain, weakness of fatigue, weight loss, fever, and night sweats. The longer it goes untreated, the higher the risk of spreading the infection to others. It is typically treated by a six-month course of four antibiotics, unless it is drug-resistant tuberculosis, which requires longer and more complex treatment. In some cases, however, the treatment can be shortened to only one or three months.

The concern over tuberculosis in Maine comes on the heels of a report about flesh-eating bacteria cases also being on the rise in the United States. In New York, an outbreak of Legionnaire's disease has been keeping health officials busy. And in California, some residents there have contracted the plague, putting health officials and residents on alert there as well.

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