Quinolones Show Promise of Much Shorter Therapy; A Match with RFP Seen

TB researchers are excited about a new generation of quinolones, a family of antibiotics well known to TB clinicians. According to a study presented at a recent meeting of researchers at the National Institutes of Health, Indian researchers conducting a clinical trial in Chennai, India, added ofloxacin -- an older quinolone -- to induction regimens containing three other first-line agents. According to "Controlled Clinical Trials for the Treatment of Sputum Positive Pulmonary Tuberculosis with Regimens Containing Ofloxacin" (TRC Annual Report 1999-2000:24), following durations of treatment ranging from the usual six months to just three, the two-month culture conversion rates ranged from 92 percent to 98 percent.

"That's unprecedented," said William J. Burman, an infectious disease specialist at the Denver Medical Health Center. "Rifampin's king, and I don't know whether even a quinolone could dethrone it," Burman conjectured, but "if something like the Chennai trials could be repeated here, does that mean we could increase two-month conversion rates by 10 percent?" If that were the case, quinolones might lead to shorter therapy or could serve in regimens entailing markedly less frequent therapy.

Researchers at the Tuberculosis Trials Consortium (TBTC) want to team a quinolone with rifapentine (RFP), the drug with the long half-life approved in 1998 for TB treatment. The TBTC is the investigator-led collaboration funded by the CDC. Rick O'Brien, MD, head of the research and evaluation branch of the CDC's Division of TB Elimination, thinks it might be possible to use quinolone along with RFP to achieve a super-short induction phase of perhaps two weeks, followed by once-weekly therapy for six months.

Ofloxacin along with a quinolone known as levofloxacin are well-respected members of second-line drugs used to treat drug-resistant disease. There are plenty of safety data on levofloxacin; however, data are scanty for long-term use of most other quinolones. According to Burman, "We've tried telling the FDA and the drug companies how we use quinolone in TB treatment all the time for long-term treatment," he said, "but they say they're still worried about side effects, and that they need more data."

The first work of the TBTC will likely be a small Phase II safety and tolerability trial that looks at two-month conversion rates. The other challenge ahead is which quinolone to use. The final hurdle is money. "If we don't get more of it, we won't be doing any trials at all on quinolones this year," said Burman.

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