New antibiotic appears effective against MDR-TB

A new antibiotic appears effective against strains of tuberculosis resistant to nearly all currently available treatments. The antibiotic, linezolid (Zyvox), recently saved the lives of four women and one girl who were gravely ill with multidrug-resistant tuberculosis at New York City’s Bellevue Hospital, according to a report by physicians from New York University School of Medicine. The patients, aged 10 to 54, were resistant to at least eight, and up to 14, TB therapies.

“They were in a lot of trouble, and we had run out of treatment options,” said William Rom MD, professor of medicine and environmental medicine at NYU School of Medicine. “Trying the linezolid was a real act of desperation,” said Timothy Harkin MD, 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,” he said.

Harkin and Rom said further studies were needed to confirm their case reports, and they hoped the drug will be tested in large clinical trials sponsored by the World Health Organisation. The NYU physicians presented the cases to colleagues at the 99th International Conference of the American Thoracic Society in Seattle.

Linezolid is a new class of antibiotic that was approved by the US Food and Drug Administration to treat certain strains of bacteria resistant to standard penicillin and methicillin and to more powerful drugs like vancomycin. It is not approved to treat drug-resistant TB. However, Bellevue 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.

Patients took linezolid twice a day in pill form for 9-33 months. Four patients also received interferon gamma in an aerosolised form three times a week. Following treatment, there was no sign of TB in sputum from the patients’ lungs. Moreover, 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 treatment, but died of unrelated causes before she could be retreated.

W Rom, T Harkin. Linezolid: A promising new agent for multi-drug resistant tuberculosis treatment. 99th International Conference of the American Thoracic Society in Seattle, Abstract P621. Presented 21 May 2003

Comment

Multi-drug resistant TB (MDR-TB) is tuberculosis resistant to isoniazid and rifampicin – the two most effective first-line anti-TB drugs – and often to additional other drugs. There are, however, at least three other first-line agents, and nine second-line agents licensed against tuberculosis, but MDR-TB remains a difficult disease to treat and is associated with high morbidity and mortality.

This early report suggests that linezolid, an oxizoladone, effective against methicillin-resistant Staphlococcus aureus (MRSA), may have in vivo activity against MDR-TB. The in vitro anti-TB activity of oxazolidones has been under investigation since the 1980s.

In this report, all five patients achieved sputum culture conversion in a mean of 40 days. However, linezolid is not without side-effects. One of the major concerns with this drug has been myelosuppression (an FDA warning was issued in March 2001), and even in this small series one patient developed neutropenia requiring temporary drug discontinuation. Linezolid cost around a $100 a day, and although further clinical studies are warranted, it may not be the ideal anti-TB drug in resource-poor settings, where the threat from MDR-TB is the greatest.