Marcos C Schechter1, Destani Bizune2, Michelle Kagei3, Mamuka Machaidze4, David P Holland1,5, Alawode Oladele6, Yun F Wang7,8, Paulina A Rebolledo1,2, Susan M Ray1, Russell R Kempker1. 1. Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine. 2. Rollins School of Public Health. 3. Emory University. 4. Department of Medicine, Emory University School of Medicine. 5. Communicable Disease Prevention Branch, Fulton County Health Department of Health and Wellness, Atlanta. 6. Dekalb County Board of Health, Decatur. 7. Department of Pathology and Laboratory Medicine, Emory University School of Medicine. 8. Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia.
Abstract
BACKGROUND: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. METHODS: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. RESULTS: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. CONCLUSIONS: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.
BACKGROUND: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. METHODS: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. RESULTS: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. CONCLUSIONS: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.
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