Newer Fluoroquinolones May Improve Outcome in Extensively Drug-Resistant TB

Alice Goodman

November 06, 2009

November 6, 2009 (Philadelphia, Pennsylvania) — There are few treatment options for extensively drug-resistant (XDR) tuberculosis (TB), but later-generation fluoroquinolones might be effective, according to one of the first studies to demonstrate a positive association for any treatment and improved XDR-TB. The study was reported at a late-breaker poster session here at the Infectious Diseases Society of America 47th Annual Meeting.

"Finding treatment regimens for XDR-TB remains a major challenge. Second-line drugs are less effective, more toxic, and more expensive than first-line therapies. By definition, XDR-TB strains are resistant to the more potent injectable agents and fluoroquinolones," explained Karen R. Jacobson, MD, from Massachusetts General Hospital in Boston.

XDR-TB is defined as resistance to isoniazid and rifampin, plus 2 of the most effective second-line TB therapies: a fluoroquinolone and an injectable agent (amikacin, capreomycin, or kanamycin).

Dr. Jacobson and colleagues conducted a meta-analysis of 13 observational studies with a total of 571 patients with XDR-TB. The studies were culled from a literature search of PubMed and EMBASE through May 2009 for all studies reporting outcomes of XDR-TB treatment.

An overall favorable effect was observed, with 43.7% of patients cured or able to complete treatment. The estimated proportion of patients who died in these trials was 20.8%.

Significantly more favorable treatment outcomes were reported in studies in which patients were treated with a later-generation fluoroquinolone, such as levofloxacin, moxifloxacin, and sparfloxacin (= .001). This effect size was a 4% increase in favorable outcomes for every additional 10% of patients treated with 1 of these 3 later-generation fluoroquinolones. Studies that included younger patients had a higher proportion of favorable outcomes (P = .004).

Current guidelines for the treatment of XDR are based on expert opinion. To strengthen the evidence for XDR-TB treatment, Dr. Jacobson called for continued testing for second-generation drug resistance, systematic reporting of treatment interventions and outcomes, and pooling of smaller cohorts.

Incorporate Later-Generation Fluoroquinolones

"This meta-analysis found that later-generation fluoroquinolones improved outcomes in XDR-TB, which by definition includes resistance to fluoroquinolones," said Brad Spellberg, MD, from Harbor UCLA Medical Center in Torrance, California. "The message seems to be that if resistance is based on treatment with an earlier-generation fluoroquinolone, a later-generation one can help."

"XDR-TB is a horrible disease. It is uniformly fatal in sub-Saharan Africa. In advanced countries, the treatment failure rate is about 50%," Dr. Spellberg said.

"For public health institutions that care for patients with this disease, a later-generation fluoroquinolone should be included as a treatment option for XDR-TB, regardless of sensitivity results from the patient's cultures," he stated.

Dr. Jacobson has disclosed no relevant financial relationships. Dr. Spellberg's reports financial ties with Merck, Astellas, Novartis, Pfizer, Arpida, Role, Theravance, Advanced Life Sciences, Novo Nordisk, and Basilea.

Infectious Diseases Society of America (IDSA) 47th Annual Meeting: Late-Breaking Poster LB-27. Presented October 31, 2009.