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Safety and Tolerability of Intermittent Rifampin/Pyrazinamide for the Treatment of Latent Tuberculosis Infection in Prisoners
To the Editor: Two months of treatment with
rifampin and pyrazinamide is effective in preventing tuberculosis (TB) in
tuberculin-positive, human immunodeficiency virus (HIV)-seropositive individuals.1-2 Recent reports, however, have
raised concerns about the safety of rifampin and pyrazinamide for latent TB
infection in HIV-seronegative individuals, although toxicity incidence is
not known.3 The reported adverse events
have occurred with use of a daily regimen. We studied the outcomes of a twice-weekly
regimen of these medications to treat latent TB in 600 prison inmates in Maryland.
Methods
From December 1, 1999 through June 30, 2001, inmates of the Maryland
Department of Public Safety and Correctional Services (DPSCS) who had a reactive
tuberculin skin test (defined as  5 mm), no radiographic evidence of active
TB, and normal aminotransferase levels, were given rifampin and pyrazinamide
twice weekly for 8 weeks. Rifampin dose was 450 mg for inmates weighing less
than 50 kg and 600 mg for those weighing 50 kg or greater. Pyrazinamide dose
was 1500 mg for inmates weighing less than 50 kg and 2500 mg for those weighing
50 kg or greater.1 Prior to treatment, a
chest radiograph, complete blood count, and measurements of uric acid, bilirubin,
and aminotransferase levels were obtained. Each medication dose was dispensed
directly to the inmate and swallowing of dose was confirmed. Each week, inmates
were asked about adverse effects and toxicities, including symptoms of hepatitis.
Bilirubin and aminotransferase levels were determined at 4 and 8 weeks.
Results
During the study period, 589 inmates were started on rifampin and pyrazinamide,
of whom 28 (5%) were known to be HIV seropositive. Five-hundred thirty-eight
(91%) completed treatment without complication; 51 (9%) discontinued treatment
for reasons including release from prison and adverse reactions. Only 10 inmates
(1.7%) experienced hepatotoxicity, of whom 9 had asymptomatic increases in
aminotransferase levels of 3 to 5 times normal. One inmate had asymptomatic
elevation of aminotransferase levels to greater than 5 times normal. He was
found to have underlying liver disease and only received 2 doses of medication.
Other adverse reactions noted included rash, nausea, and vomiting. A review
of the Maryland Department of Health and Mental Hygiene Tuberculosis Registry
on February 13, 2002 found no subsequent cases of tuberculosis among any of
the 589 inmates treated.
Comment
We achieved a 91% completion rate for the treatment of latent TB in
prison inmates. By comparison, between 1995 and November 1999, only 64% of
almost 1800 DPSCS inmates started on a 6-month regimen of isoniazid completed
treatment (DPSCS, unpublished data, 1999). Our completion rate was also substantially
higher than the 48% reported by Bock et al4
in jail inmates, presumably because the length of incarceration for the latter
was shorter than for our inmates.
Twice-weekly rifampin and pyrazinamide was well tolerated, with no cases
of symptomatic hepatitis and few increases in aminotransferase levels. This
is consistent with the experience with this regimen when given intermittently
or daily to HIV-infected patients in Haiti1
and in a multinational trial.2 Several possible
reasons for the low toxicity of the regimen in this setting are the low dose
of pyrazinamide (average, 30 mg/kg twice weekly) and the careful pretreatment
evaluation and ongoing monitoring used throughout therapy. It is not known
if a higher dose of twice-weekly pyrazinamide, such as the 50 mg/kg dose recommended
by the American Thoracic Society and the US Centers for Disease Control and
Prevention,5 is more efficacious than the
dose we used. Based on passive surveillance with relatively limited follow-up,
we have observed no cases of TB in this inmate cohort to date.
Our experience suggests that intermittent rifampin and pyrazinamide
for latent TB infection is extremely well tolerated and results in substantially
higher completion rates in prison inmates than with longer courses of isoniazid.
Additional studies of the safety and tolerability of both daily and twice-weekly
use of this regimen in HIV-seronegative individuals will be useful.
Richard E. Chaisson, MD
Johns Hopkins University School of Medicine
Baltimore, Md
Joan Armstrong, RN
Maryland Department of Public Safety and Correctional Services
Towson
John Stafford, MD, MPH
Maryland Department of Public Transportation
Baltimore-Washington International Airport
Jonathan Golub, MPH;
Sarah Bur, RN, MPH
Maryland Department of Health and Mental Hygiene
Baltimore
1. Halsey NA, Coberly JS, Desormeaux J, et al. Randomised trial of isoniazid versus rifampin and pyrazinamide for
the prevention of tuberculosis in HIV-1 infection. Lancet. 1998;351:786-792.
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2. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis
in HIV-infected persons: an international randomized trial. JAMA. 2000;283:1445-1450.
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3. US Centers for Disease Control and Prevention. Update: fatal and severe liver injuries associated with rifampin and
pyrazinamide for latent tuberculosis infection, and revisions in American
Thoracic Society/CDC recommendations—United States, 2001. MMWR Morb Mortal Wkly Rep. 2001;50:733-735.
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4. Bock NN, Rogers T, Tapia JR, et al. Acceptability of short-course rifampin and pyrazinamide treatment of
latent tuberculosis infection among jail inmates. Chest. 2001;119:681-682.
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5. American Thoracic Society/Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.
Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
JAMA. 2002;288:165-166.
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