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  • Title: Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus?
    Author: Tortajada C, Martínez-Lacasa J, Sánchez F, Jiménez-Fuentes A, De Souza ML, García JF, Martínez JA, Caylà JA, Tuberculosis Prevention Working Group.
    Journal: Int J Tuberc Lung Dis; 2005 Mar; 9(3):276-81. PubMed ID: 15786890.
    Abstract:
    SETTING: Nine public health care centres in four Spanish cities. OBJECTIVE: To evaluate the efficacy and safety of 2 months of rifampicin (R) plus pyrazinamide (Z) therapy (2RZ) compared with a 6-month course of isoniazid therapy (6H) for treating latent tuberculosis infection (LTBI). DESIGN: Multicentered, randomised, comparative and prospective trial conducted in HIV-seronegative contacts of infectious pulmonary TB cases. RESULTS: Of 352 individuals, 199 received 6H and 153 2RZ; 73% of contacts receiving 6H and 71% receiving 2RZ completed treatment (P = 0.73). Treatment interruption due to hepatotoxicity (ALT/AST > 5 times upper limit of normal) was observed in 10% of contacts in the 2RZ group and in 2.5% of the 6H group (P = 0.007). This higher than expected rate of hepatotoxicity in the 2RZ arm led to premature termination of the study. Severe or fatal liver injury was not detected. Liver function tests normalised after discontinuation of treatment. We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible.
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