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Clinical Investigations: TUBERCULOSIS |

Initial Experience on Rifampin and Pyrazinamide vs Isoniazid in the Treatment of Latent Tuberculosis Infection Among Patients With Silicosis in Hong Kong*

Chi Chiu Leung; Wing Sze Law; Kwok Chiu Chang; Cheuk Ming Tam; Wing Wai Yew; Chi Kuen Chan; Man Yee Wong
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*From the Tuberculosis Service (Drs. Leung, Law, Chang, Tam, Chan, and Wong), Department of Health, Pneumoconiosis Clinic; and Tuberculosis and Chest Unit (Dr. Yew), Grantham Hospital, Hong Kong, China.

Correspondence to: Chi Chiu Leung, MB, FCCP, Pneumoconiosis Clinic, 8 Chaiwan Rd 4/F, Shaukiwan, Hong Kong, China; e-mail: cc_leung@dh.gov.hk



Chest. 2003;124(6):2112-2118. doi:10.1378/chest.124.6.2112
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Objective: To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H).

Background: Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis. A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half.

Method: Patients with silicosis and a Mantoux skin test reaction ≥ 10 mm were randomized to receive either 2RZ or 6H daily. Liver function testing was done monthly during the initial 2 months. The adverse effects and treatment adherence were compared between the two regimens.

Results: Forty patients (mean age, 61.6 ± 9.1 years) and 36 patients (mean age, 57.6 ± 9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [± SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%, p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven patients had symptoms suggestive of hepatitis; none of the patients had jaundice. All recovered after withholding treatment. In the 2RZ study arm, none of the baseline characteristics predicted hepatotoxicity. Other adverse effects were generally mild and comparable between both study arms. Treatment was stopped prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm.

Conclusion: A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.

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