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Moxifloxacin Instead of Isoniazid for Pulmonary TB?

In a multinational trial, rates of culture negativity after 2 months of therapy were similar between the two drugs.

Moxifloxacin has a long serum half-life, causes few problematic drug interactions, and requires no dosage adjustment for renal or hepatic insufficiency. In a mouse model of TB, substitution of moxifloxacin for isoniazid (INH) reduced the time to lung sterilization and allowed therapy to be shortened to 4 months. Could moxifloxacin be substituted for INH in the treatment of active pulmonary TB in humans?

To find out, Tuberculosis Trials Consortium researchers conducted a double-blind trial involving adults during their first 2 months of combination therapy for active pulmonary TB. A total of 328 participants were randomized to receive either moxifloxacin (400 mg) or INH (300 mg) 5 days per week for 8 weeks, in addition to rifampin, pyrazinamide, ethambutol, and pyridoxine. Sixty-five percent of the participants were enrolled at African sites; the rest were in North America, Brazil, or Spain.

The primary efficacy endpoint — culture negativity after 8 weeks of treatment — was achieved for 60% of moxifloxacin-group patients and 55% of INH-group patients (P=0.37). Discontinuation rates were similar between groups (15% and 11%, respectively; P=0.25). Nausea, however, was more common in moxifloxacin-group patients (P=0.03).

Comment: In contrast to the mouse model, and to a previous study in which moxifloxacin was substituted for ethambutol (JW Infect Dis Apr 15 2009), this study does not show an advantage for moxifloxacin. The findings do suggest, however, that moxifloxacin might be a suitable alternative for patients who are intolerant of INH or are infected with INH-resistant Mycobacterium tuberculosis.

— Neil M. Ampel, MD

Published in Journal Watch Infectious Diseases August 19, 2009

Citation(s):

Dorman SE et al. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. Am J Respir Crit Care Med 2009 Aug 1; 180:273.

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• What about Contacts of tuberculosis patients?
  Dr Suresh Amin, Baroda , India, 20 Aug 2009 12:15 PM EST
  Isoniazid is often prescribed for close contacts, or "careers." Has efficacy of moxifloxacin been tried in terms of time interval... [more]