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. 2017 Nov 13;65(11):1862-1871.
doi: 10.1093/cid/cix686.

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia

Marcos C Schechter  1 , Destani Bizune  2 , Michelle Kagei  3 , Mamuka Machaidze  4 , David P Holland  1   5 , Alawode Oladele  6 , Yun F Wang  7   8 , Paulina A Rebolledo  1   2 , Susan M Ray  1 , Russell R Kempker  1
Affiliations

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia

Marcos C Schechter et al. Clin Infect Dis. .

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.

Keywords: fluoroquinolones; isoniazid resistance; time to sputum culture conversion; tuberculosis.

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Figures

Figure 1.
Figure 1.
Study population flow diagram. Abbreviation: MDR, multidrug-resistant.
Figure 2.
Figure 2.
Culture-confirmed pulmonary tuberculosis cases per year. Numbers above graph represent percentage of isoniazid-resistant cases per year.
Figure 3.
Figure 3.
Cumulative sputum culture conversion by isoniazid resistance status. Abbreviations: CI, confidence interval; HR, hazard ratio.
See this image and copyright information in PMC

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