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. CONCLUSION: These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.