INH monotherapy was compared with combination INH and rifampin in a 2005 meta-analysis of 5 RCTs of variable quality involving 1926 patients.7 This meta-analysis found equivalency in risk of active TB and mortality between INH monotherapy for 6 to 12 months and the combination of rifampin and INH for 3 months (pooled risk difference=0%; 95% confidence interval [CI], –1% to 2%). This study also showed similar rates of adverse events in both groups (pooled risk difference=–1%; 95% CI, –7% to 5%). Short-course combination rifampin and pyrazinamide is no longer recommended after an open-label RCT with 589 patients demonstrated severe hepatoxicity in 7.7% (16/207) on a 2-month course of pyrazinamide and rifampin, compared with 1% (2/204) on 6 months of INH (RR=7.9, number needed to harm=15).8 Rifampin monotherapy has only been studied in patients with silicosis in a RCT enrolling 652 participants with latent tuberculosis. A 12-week course of rifampin (600 mg daily) was as effective as 6 months of INH in preventing development of active TB over the next 5 years.9
FIGURE
Suggested workup of asymptomatic, HIV-negative patients with a positive PPD
Source: Am J Respir Crit Care Med 2000;2 Jasmer et al, N Engl J Med 2002.3
Recommendations from others
Centers for Disease Control and Prevention, American Thoracic Society, and Infectious Disease Society of America guidelines recommend targeted screening of high-risk persons followed by further clinical evaluation of all those with a reactive PPD (FIGURE).2,10 The recommended treatment regimen for latent TB is daily INH for 9 months. Less preferable regimens are daily INH for 6 months, or daily rifampin for 4 months in patients who cannot tolerate INH. A 2-month course of rifampin and pyrazinamide is no longer recommended. The recent meta-analysis supporting a 3-month regimen of combination INH and rifampin has not been incorporated into expert guidelines.7