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A new antibiotic appears effective against multidrug-resistant TB


A new antibiotic appears effective against deadly strains of tuberculosis resistant to nearly all currently available treatments for the infectious disease. The antibiotic, called linezolid, recently saved the lives of four women and one girl who were gravely ill with multidrug-resistant tuberculosis and who were hospitalized at Bellevue Hospital in New York City, according to a report by physicians at NYU School of Medicine. The patients, ranging in age from 10 to 54, were resistant to at least eight, and up to 14, anti-TB therapies.

"This group of patients were our most difficult to treat," says William Rom, M.D., Professor of Medicine and Environmental Medicine at NYU School of Medicine. "They were in a lot of trouble, and we had run out of treatment options."

Dr. Rom is also Chief of the Chest Service at Bellevue Hospital, an affiliate of NYU Medical Center. Bellevue’s Chest Service, which recently celebrated its 100th anniversary, is regarded as the birthplace of pulmonology. Chest Services originally were devoted to patients with TB, a disease that targets the lungs.

"Trying the linezolid was a real act of desperation," says Timothy Harkin, M.D., Assistant Professor of Medicine and Assistant Director of Bellevue’s Chest Service. "This certainly seems like a promising medication for multidrug-resistant TB and there is a continuing need for new antibiotics for this disease."

Drs. Harkin and Rom say that further studies are needed to confirm their case reports, and hope the drug will be tested in large clinical trials sponsored by the World Health Organization. The NYU physicians presented the cases to their colleagues on Wednesday, May 21, at an international conference held by the American Thoracic Society in Seattle.

Multidrug-resistant TB is pandemic and certain places in the world, such as Eastern Europe, Estonia, Latvia, and jails in Russia, are regarded as hot spots where the prevalence is alarmingly high. No new drugs that might be effective in treating resistant strains are in clinical trials, and many researchers are not optimistic that new therapies will be available anytime soon.

Tuberculosis is one of the world’s greatest killers, taking the lives of two million people each year. Some eight million new cases of TB arise each year and currently more than one-third of the world’s population is infected with the bacterium causing TB, according to the World Health Organization. The microbe can lie dormant for decades, and then suddenly activate and attack the lungs (producing a bloody cough), the spinal cord, kidney and other parts of the body.

Typically, TB is cured with six months of therapy with antibiotic pills. But drug-resistant strains of the bug require 18 to 24 months of treatment with powerful multidrug regimens along with medical support to manage the regimens’ side effects. The cost of treatment for drug-resistant TB exceeds $250,000, which is up to 20 times the cost of the standard six-month therapy. Drug resistant strains of the bug arise when patients do not finish the entire course of their therapy or are treated with the wrong combination of drugs.

Linezolid (brand name Zyvox) is a new class of antibiotics that was approved by the Food and Drug Administration to treat certain strains of bacteria resistant to standard antibiotics such as penicillin and methicillin, and to more powerful drugs like vancomycin. It is not approved to treat drug-resistant TB.

However, Bellevue Chest Service doctors decided to try linezolid when all other available therapies, including the most powerful drugs yet available for drug-resistant TB, failed to improve the health of the five patients at Bellevue. Linezolid had been shown in laboratory studies to have an effect against the TB microbe.

The patients took linezolid twice a day in pill form for nine to 33 months. Four patients also received interferon gamma (a type of immune system modulator) in an aerosolized form three times a week. Following the treatment, there was no sign of the TB microbe in sputum from the patients’ lungs. Moreover, the physicians said that the drug did not seem to be associated with many severe side effects. Two patients continue on treatment and are doing well. One patient relapsed two years after completing the treatment, but died of unrelated factors before she could be re-treated.

In the early 1990s, New York City was the epicenter of a TB resurgence in the United States, fueled partly by the HIV epidemic, a deteriorating public health infrastructure, and an increase in poverty and homelessness. Insufficient treatment led to an alarming rise in drug-resistant strains of the disease. At its peak in 1992, New York City reported 441 drug-resistant cases out of 3,811 new cases of TB in the city. Since that time, the number of cases has decreased dramatically after a concerted effort was made to ensure that all patients took their medications for the fully prescribed period of time through a method called directly observed therapy. In 2001, the latest year for which data is available, 24 patients had multidrug-resistant strains of TB out of 1,261 new cases of TB reported in New York City.

In addition to Drs. Rom, Harkin, the other NYU School of Medicine physicians who collaborated on the case reports are: Nicos Hadjiangelis, M.D., a pulmonary and critical care fellow, Eric Leibert, M.D., Assisant Professor of Clinical Medicine, and Rany Condos, M.D., Assistant Professor of Medicine.

Pamela McDonnell | EurekAlert!
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