Impact of isoniazid resistance-conferring mutations on the clinical presentation of isoniazid monoresistant tuberculosis.
BACKGROUND
Specific isoniazid (INH) resistance conferring mutations have been shown to impact the likelihood of tuberculosis (TB) transmission. However, their role in the clinical presentation and outcomes of TB has not been evaluated.


METHODS
We included all cases of culture-confirmed, INH monoresistant tuberculosis reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005. For cases with stored culture isolates, we used polymerase chain reaction (PCR) testing and gene sequencing to identify INH resistance-conferring mutations, and compared genotypic and phenotypic characteristics.


RESULTS
Among 101 consecutive cases of INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%) had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with other mutations. The katG S315T mutation was independently associated with high-level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07-2.27), and the inhA-15;c-t promoter mutation was inversely associated with high-level INH resistance (RR 0.43, 95% CI 0.21-0.89). However, specific INH resistance-conferring mutations were not associated with the clinical severity or outcomes of INH monoresistant TB cases.


CONCLUSIONS
These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.
Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America. raydantes@gmail.com
Raymund
R
Dantes
John
J
Metcalfe
Elizabeth
E
Kim
Midori
M
Kato-Maeda
Philip C
PC
Hopewell
Masae
M
Kawamura
Payam
P
Nahid
Adithya
A
Cattamanchi
D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007538:Isoniazid; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012495:San Francisco; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D018709:Statistics, Nonparametric; D014376:Tuberculosis / Q000235:genetics* / Q000635:transmission*
D001426:Bacterial Proteins; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D007538:Isoniazid