Small Study Suggests Linezolid Effective for Multidrug-Resistant TB

Peggy Peck

May 22, 2003

May 22, 2003 (Seattle) — Linezolid, the oxazolidinone approved for treating methicillin-resistant Staphylococcus aureus pneumonia and vancomycin-resistant Enterococcus faecium, shows promise for treatment of multidrug resistant tuberculosis (MDR-TB), according to researchers at New York University School of Medicine.

Nicos Hadjiangelis, MD, fellow in pulmonary and critical care medicine at NYU School of Medicine/Bellevue Chest Service in New York City, told Medscape that "five of five patients treated with linezolid achieved culture conversion in an average of 40 days." One patient converted in "just 7 days," he said. He presented results of the retrospective analysis of the small series here yesterday at the American Thoracic Society (ATS) 99th International Conference.

Rick O'Brien, MD, of the department of TB prevention at the Centers for Disease Control and Prevention in Atlanta, Georgia, said he is pleased to see some centers investigating linezolid since "we've been looking at oxazolidinones since the late 1980s, when we recognized that they had some activity in TB." The drug's reported adverse effects include bone marrow suppression; the US Food and Drug Administration issued a myelosuppression warning for linezolid in March 2001. "That is one problem...and I think that even in this small study, one patient had the drug stopped because of toxicity," said Dr. O'Brien, who was not involved in the NYU study.

Dr. Hadjiangelis said one patient developed neutropenia, which resolved when the drug was stopped. "That patient was then restarted on the drug and was successfully treated," he said.

All patients were resistant to isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin and either ciprofloxacin or capreomycin or both, he said. Three patients had prior pneumonectomies and an HIV-positive patient had undergone pericardiectomy, while a hepatitis C-infected patient had received a liver transplant.

The patients, all of whom were female aged 10 to 54 years, received linezolid, 600 mg orally twice a day for 4 to 33 months and aerosol interferon-gamma therapy (4 of 5 patients) three times a week in addition to their failing drug regimen. "There are no data on therapeutic dose for TB, so we used the same dose that is used for treatment of pneumonia," Dr. Hadjiangelis said.

Otto Braendli, MD, director of the tuberculosis center at Faltigberg Hospital in Zurich, Switzerland, questioned the twice-daily regimen. He noted that he has had success with "just a single pill a day. In TB, the 'bug' does not grow so fast, so once-a-day treatment is effective and less expensive."

Twice-daily treatment with linezolid adds about $100 a day to treatment costs, according to Richard Wunderick, MD, director of research at Methodist University Hospital and clinical associate professor of medicine at the University of Tennessee, both in Memphis. Earlier at the ATS meeting, Dr. Wunderick presented findings from a study that compared linezolid to vancomycin for MRSA pneumonia. While Dr. O'Brien agreed that linezolid adds cost to treatment, he said that "once a day or twice a day probably does not make a difference in response."

Two of the five patients have completed 24 months of linezolid treatment and "are still in remission," two more are still taking linezolid and remain in remission, and the fifth patient died "but [the] death was from an unrelated condition," Dr. Hadjiangelis said.

Dr. O'Brien said that a large prospective study is needed, but "in the meantime, it is encouraging to receive reports from small series, like this one."

ATS 99th International Conference: Abstract P621. Presented May 21, 2003.

Reviewed by Gary D. Vogin, MD