Short-Course Rifampin and Pyrazinamide Compared with Isoniazid for Latent Tuberculosis Infection: A Multicenter Clinical Trial

Jasmer, Robert M.; Saukkonen, Jussi; Blumberg, Henry M.; Daley, Charles L.; Bernardo, John; Vittinghoff, Eric; King, Mark D.; Kawamura, L. Masae; Hopewell, Philip C.

doi:10.7326/0003-4819-137-8-200210150-00007

Cited by 177 publications

(113 citation statements)

References 16 publications

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“…Three controlled clinical trials of rifampin and pyrazinamide in HIV-infected adults with latent TB found that this regimen was as well or better tolerated as INH, with extremely low rates of liver toxicity (7-9); yet, two clinical trials in HIV-uninfected adults noted serious hepatotoxicity in 7 to 10% of patients taking this regimen (22,25). Our results confirm these findings.…”

Section: Discussionsupporting

confidence: 81%

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Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Schechter

Zajdenverg

Falco

et al. 2006

Am J Respir Crit Care Med

129

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Rationale: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. Objectives: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil. Methods: Contacts of patients with TB were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450-600 mg/pyrazinamide 750-1,500 mg daily for 8 wk and followed for at least 2 yr. Measurements: TB rates, adverse events, and adherence to therapy. Main Results: A total of 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 yr, median weight was 63 kg, 60% of participants were female, and only one patient was HIV infected. Rifapentine/isoniazid was well tolerated, but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. Twenty of 193 participants (10%) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity, compared with 2 of 206 participants (1%) on rifapentine/isoniazid (p Ͻ 0.001). There were no hospitalizations or deaths due to hepatotoxicity, and all participants' liver enzyme levels returned to normal during follow-up. During followup, four cases of active TB developed, three in the rifapentine/ isoniazid group and one in the rifampin/pyrazinamide group (1.46 vs. 0.52%; difference, 0.94%; 95% confidence interval, Ϫ1.6 to 3.7%). Conclusions: Rifapentine/isoniazid was better tolerated than rifampin/ pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.Keywords: controlled clinical trial; latent tuberculosis; pyrazinamide; rifampin; rifapentine Treatment of latent Mycobacterium tuberculosis infection is an important component of tuberculosis (TB) control (1, 2) In Western countries, targeted testing and treatment of latently infected individuals is recommended for those at increased risk of developing active TB, including contacts of infectious cases, individuals with HIV infection and other conditions that reduce host resistance to TB, and immigrants from endemic areas, among others (1). Chemoprophylaxis of high-risk patients using isonia- zid (INH) reduces the risk of developing active disease by 60 to 90%, and is the standard of care throughout the world (3). Although INH preventive therapy is highly efficacious and inexpensive, its use may be limited by toxicity and poor adherence with the long duration of treatment required for patients with no symptoms. Consequently, the development of alternative, shorter regimens to treat latent TB infection has become a priority (4).Rifamycin antibiotics have greater potency against the dormant and semidormant organisms that characterize latent TB infection than INH alone, and may be effective when given for shorter duration...

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Section: Discussionsupporting

confidence: 81%

“…This rate of rifampin and pyrazinamide toxicity is comparable to rates reported in recent years from several observational studies and two clinical trials in individuals without HIV infection (23)(24)(25)(26)(27)(28)(29), but is substantially higher than rates reported in clinical trials of patients with HIV infection (7)(8)(9).…”

Section: Discussionsupporting

confidence: 47%

Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts

Schechter

Zajdenverg

Falco

et al. 2006

Am J Respir Crit Care Med

129

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“…Several regimens have been tried to re-introduce ATT, some starting with isoniazid and others with rifampicin or pyrazinamide. In general, pyrazinamide containing regimens have been found more hepatotoxic [27,28,29,30]. We were able to safely reintroduce isoniazid and rifampicin in most of our patients (96% and 88% respectively) after recovery from hepatitis.…”

Section: Discussionmentioning

confidence: 64%

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Anand

Seth

Paul³

et al. 2006

Medical Journal Armed Forces India

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Background: Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. Methods: Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher's exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. Results: Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATTinduced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. Conclusion: ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases. MJAFI 2006; 62 : 45-49

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“…64 This can be gleaned from the high rates of toxicity including death in patients treated with rifampicin-pyrazinamide combination for latent tuberculosis. 65 …”

Section: Concomitant Medication or Polypharmacymentioning

confidence: 99%