Case raises fears about spread of drug-resistant TB

A new report on a patient in Switzerland who nearly died after catching a highly drug-resistant strain of tuberculosis illustrates exactly what public health officials around the world fear most.

Although antibiotics have largely eradicated tuberculosis in the United States in recent decades, experts say evidence is mounting that the bacteria is becoming increasingly resistant to these medications.

Details of the Swiss case are reported in the Nov. 12 issue of the New England Journal of Medicine by lead investigator Sebastien Gagneux, head of tuberculosis research with the Swiss Tropical and Public Health Institute at the University of Basel, and colleagues.

Normally, Gagneux said, tuberculosis patients are treated for six months with a daily drug "cocktail" comprised of four different first-line medications.

The goal: to hem in tuberculosis (TB) while reducing the risk of drug resistance.

Even so, "antibiotic resistance is inevitable," he added. "Bacteria fights for its life, and does what it has to do, adapting to survive. And with time, overuse or inappropriate use of antibiotics also plays a role. And in the case of TB, this has been happening while pharmaceutical companies have essentially come out with no new antibiotic treatments for TB for more than 40 years."

The result: almost half a million patients are now infected with multidrug-resistant TB every year, according to the medical organization Doctors Without Borders. This means their illness is impervious to the two strongest first-line antibiotics typically used.

Even worse, the organization projects that roughly 10 percent of multidrug-resistant patients are actually infected with extensively drug-resistant TB, which renders many first- and second-choice antibiotics ineffective.

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Although American cases involving drug resistance remain rare, mounting concern about drug-resistant TB prompted the U.S. Food and Drug Administration to issue limited approval for the clinical use of an experimental antibiotic known as bedaquiline (Sirturo) in 2012. At the same time, another experimental medication called delamanid was given provisional approval by the European Medicines Agency. Both are still undergoing testing for safety and effectiveness, and they are intended for use only in cases when all other options fail.

Such was the case with the patient in Switzerland, who was diagnosed in 2010 with a strain of TB that was resistant to seven different first- and second-choice antibiotics.

Between 2011 and 2012, the patient was given bedaquiline, alongside four standard antibiotics, and by 2013 he was considered to be free of the disease, the researchers said.

However, five months after his treatment ended, the patient had a relapse, at which point his infection was deemed to be bedaquiline-resistant.

In 2014, he was then given delamanid. But again, resistance developed within a matter of months, the researchers said.

The patient then had surgery to remove the affected part of his lung, "and that is really what saved his life," said Gagneux.

"So really, this case suggests that we're dealing with a serious public health threat," he added. "It's rare. Most people won't get drug-resistant TB. But for those who do, the risk of drug failure is real. And frankly, it has been such a long time since we last saw new and proven drugs coming online that it's going to be quite difficult to play catch up."

Dr. Philip Tierno, a professor of microbiology and pathology at the NYU School of Medicine in New York City, agreed.

"Yes, this kind of drug resistance is very, very rare. But TB affects huge swaths of the world's population. Literally billions of people are infected. It blows the mind. Now, most will never have symptoms and will not pose an infection risk to others. But that still means millions will get sick," Tierno said.

"And the fear is that they increasingly get sick with strains of TB that are resistant to the drugs we have available before we have time to develop new drugs," he added. "That's a real problem. No question about that."

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