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1 Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Samsung Medical Center, and 2 Korea Institute of Tuberculosis, Korea National Tuberculosis Association, Seoul, South Korea.
To the Editors:
Several treatment regimens have been recommended for the treatment of isoniazid-resistant tuberculosis (TB). However, an optimal regimen and duration for this treatment remains a matter of some controversy. Here, we would like to share our experience in a case of pulmonary TB with acquired multidrug resistance, during a 12-month treatment of isoniazid-resistant TB with rifampin and ethambutol, with pyrazinamide administered during the initial 2 months.
A 55-yr-old male visited the outpatient chest clinic for the evaluation of a chronic cough. The patient had diabetes mellitus, which had been controlled with oral hypoglycaemic agents. The patient had no history of TB. His chest radiography revealed cavitary consolidation in the left upper lobe. Several sputum samples revealed a host of acid-fast bacilli. Daily anti-TB therapy was initiated with isoniazid, rifampin, ethambutol and pyrazinamide. After 2 months of this treatment, the regimen was changed to isoniazid, rifampin and ethambutol, at which time cultured isolates of Mycobacterium tuberculosis were processed for drug susceptibility testing. After 3 months of therapy, the results of drug susceptibility tests indicated high-grade resistance to isoniazid. Isoniazid was discontinued and rifampin and ethambutol were continuously administered on a daily basis. Monthly monitored sputum cultures for acid-fast bacilli converted to negative after 2 months of treatment. The total treatment duration was initially scheduled for a full 12 months. After 10 months of therapy, however, an additional sputum culture revealed the growth of 20 colonies of M. tuberculosis. A drug-susceptibility test revealed the development of resistance to both isoniazid and rifampin, as well as susceptibility to other drugs. After this, a sputum smear for acid-fast bacilli was, once again, positive.
Previous studies have suggested that standard 6-month, four-drug regimens may be effective in the treatment of isoniazid-resistant TB 1. In recent years, however, many published guidelines for the treatment of TB have stated that it would be more prudent either to administer pyrazinamide continuously throughout the 6 months, or to prolong the duration of treatment 2–4.
If drug-susceptibility test results are available before the end of the 2 month initial phase of treatment, isoniazid should be discontinued and pyrazinamide should be continued for the entire 6-month duration of therapy (6REZ) 2, 3. If isoniazid resistance is documented during the 9-month regimen without pyrazinamide, or in the 6-month regimen during the continuation phase of treatment, treatment with rifampin and ethambutol should be continued for a minimum of 12 months (12RE or 2REZ/10RE) 2, 4.
The effectiveness of these recommended regimens has not, until now, been well evaluated. One retrospective study has revealed that a 6-month daily regimen involving the administration of isoniazid, rifampin, ethambutol and pyrazinamide (6HREZ) proved highly effective 5. However, the effectiveness of the 12-month regimen of rifampin and ethambutol, with or without pyrazinamide during the initial 2 months, has not been evaluated until now.
In patients with isoniazid-resistant tuberculosis, who also have manifested extensive bilateral disease or cavitation on chest radiographs, the development of acquired rifampin resistance could be possible during treatment with rifampin and ethambutol. Our report underlines the seriousness of the concerns regarding the development of multidrug-resistant tuberculosis in patients infected with a Mycobacterium tuberculosis strain with primary isoniazid resistance during treatment with rifampin and ethambutol for 12 months, especially in the cases in which the patient exhibits cavitary pulmonary tuberculosis.
REFERENCES
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