Newly Diagnosed TB Patients at Risk of Fluoroquinolone Resistance

Peggy Peck

May 22, 2003

May 22, 2003 (Seattle) — Just as infectious disease specialists are considering fluoroquinolones as first-line agents for treatment of tuberculosis (TB), a study from Johns Hopkins University School of Medicine suggests that newly diagnosed TB patients might have fluoroquinolone resistance as the result of the wide use of fluoroquinolones for bacterial infections.

Lead investigator Amy S. Ginsburg, MD, MPH, told Medscape that "typically TB is not the first diagnosis for patients, so often they were initially diagnosed with pneumonia or another community-acquired infection and receive a fluoroquinolone to treat it." Dr. Ginsburg said her small retrospective study found that 4% of newly diagnosed M. tuberculosis patients had decreased susceptibility to fluoroquinolones. Dr. Ginsburg presented the study here yesterday at the American Thoracic Society 99th International Conference.

The researchers reviewed all culture-confirmed TB cases diagnosed in adults at Johns Hopkins from January 1998 to March 2002. After excluding patients for whom data on antimicrobial use was not available, they identified 55 patients.

"A significant number of these patients — 19 — had received fluoroquinolone monotherapy prior to the initiation of TB treatment," she said. The average duration of fluoroquinolone monotherapy was 4 days with a range of 2 to 9 days of treatment. Two of these patients developed fluoroquinolone resistance. "None of the 36 patients who did not have prior fluoroquinolone therapy had diminished susceptibility to the agent," she said.

Both of the fluoroquinolone-resistant patients had AIDS, she said. One patient had a CD4+ cell count of 40 cells/mm 3 while the other patient's CD4+ cell count was 39 cells/mm 3. "This is interesting since HIV coinfection in TB is associated with isoniazid and rifampin resistance," said Dr. Ginsburg.

She noted that a multicenter trial of moxifloxacin as first-line therapy is currently underway, so determining the rate of fluoroquinolone resistance in the community is of concern.

Rick O'Brien, MD, from the department of TB prevention at the Centers for Disease Control and Prevention in Atlanta, Georgia, told Medscape that there is little doubt that "moxifloxacin is the hot drug in TB." He noted that the Johns Hopkins investigators also reported at ATS a mouse model treatment with moxifloxacin, which "achieved sterile cultures at three months.

"But Amy Ginsburg's paper is the downside of moxifloxacin. Fluoroquinolones are out there in the community and are being regularly prescribed for bacterial infections," Dr. O'Brien said. That widespread use may limit the potential of moxifloxacin. Dr. O'Brien was not involved in the study, but he was a featured speaker at the poster discussion session at which it was presented.

Although Dr. Ginsburg noted that her study is limited by both its size and the fact that it is a retrospective review, she said "the findings do suggest that clinicians should, at the minimum, not assume that patients are fluoroquinolone naive before initiating TB treatment with this agent."

The study was funded by the National Institute of Allergy and Infectious Diseases.

ATS 99th International Conference: Abstract P611. Presented May 21, 2003.

Reviewed by Gary D. Vogin, MD

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