Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics.
METHODS
Three municipal tuberculosis (TB) clinics.


OBJECTIVE
Reports of liver injury in patients treated with a 2-month regimen of daily rifampin and pyrazinamide (2RZ) for latent TB infection have raised concern about its safety. We aimed to evaluate the safety and tolerability of 2RZ and identify risk factors for hepatotoxicity.


METHODS
We reviewed charts of adults started on 2RZ between 1999 and 2001. Cases with grade 3 hepatotoxicity (AST or ALT >5.0-20.0 x upper limit of normal) and grade 4 hepatotoxicity (AST or ALT >20.0 x upper limit of normal) were identified.


RESULTS
Of 148 patients prescribed 2RZ, 85 (57.4%) completed therapy. Grade 3 or 4 hepatotoxicity occurred in 14 patients (eight grade 4 cases). In multivariate analysis, hepatotoxicity was associated with female sex (odds ratio [OR] 4.1; 95% confidence interval [CI] 1.2-14.3) and with presumed recent infection (recent tuberculin skin test conversion or contact with a TB case) (OR 14.3; 95%CI 1.8-115), but not with alcohol use, illicit drug use, age, race, or pyrazinamide dose.


CONCLUSIONS
Hepatotoxicity occurred in a high proportion of patients prescribed 2RZ, and was more common among females and those with recent infection. Caution is warranted in using 2RZ in populations where its safety has not been established.
Lee
A M
AM
Communicable Disease Program, Chicago Department of Public Health, Chicago, IL 60612, USA.
Mennone
J Z
JZ
Jones
R C
RC
Paul
W S
WS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000554:Ambulatory Care Facilities; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002641:Chicago; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D006779:Hospitals, Public; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011718:Pyrazinamide / Q000009:adverse effects*; D012189:Retrospective Studies; D012293:Rifampin / Q000009:adverse effects*; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D011718:Pyrazinamide; D012293:Rifampin