Study objective: The standard daily
dose of rifampin in directly observed treatment of Mycobacterium
tuberculosis (TB) is 600 mg, taken orally. The purpose of this
study was to assess the efficacy of standard dose rifampin therapy in
patients who were slow to respond to routine directly observed therapy
Methods: Patients with non-drug-resistant
pulmonary TB who were receiving 600 mg of oral rifampin by DOT were
eligible for inclusion. Patients were deemed slow to respond if their
sputum smears and cultures remained positive for M
tuberculosis and if the patient’s condition did not improve
clinically or radiographically after 3 months of treatment. Serum
rifampin levels were ascertained to determine the adequacy of the
standard rifampin dosing. Patients with subtherapeutic blood levels had
their rifampin dose increased to 900 mg, and rifampin levels were
repeated. Rifampin dosage was increased again if blood levels were
still subtherapeutic. No antitubercular medications were added to the
treatment regimen. The total weekly dose of the other standard
treatment drugs was not increased.
Results: Of 124 new
patients with active pulmonary TB, 6 patients were identified as slow
to respond to the standard antitubercular DOT. All six patients had
subtherapeutic serum rifampin levels. All six patients responded
clinically, radiographically, and mycobacteriologically after an
increase in rifampin dosage to reach target drug blood level.
Conclusions: Standard dosing with rifampin resulted in a
poor clinical response and subtherapeutic serum levels in six patients.
Increasing the dosage of rifampin improved the outcome without
additional side effects. In TB patients who are slow to respond to
standard treatment, an inadequate dose of rifampin should be suspected.
Current antituberculer drug administration does not include adjusted
dosage for rifampin.