Amyn A Malik1,2,3, Mercedes C Becerra4,5,6, Timothy L Lash1, Lisa M Cranmer7, Saad B Omer8,9,10, Junaid Fuad2, Sara Siddiqui2, Farhana Amanullah11, Maria Jaswal2, Naseem Salahuddin11, Salmaan Keshavjee4,5,6, Hamidah Hussain3, Neel R Gandhi1. 1. Emory University Rollins School of Public Health, Atlanta, Georgia, USA. 2. Global Health Directorate, Indus Health Network, Karachi, Pakistan. 3. Interactive Research and Development Global, Singapore. 4. Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, USA. 5. Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA. 6. Partners In Health, Boston, Massachusetts, USA. 7. Emory University School of Medicine, Atlanta, Georgia, USA. 8. Yale Institute for Global Health, New Haven, Connecticut, USA. 9. Yale School of Medicine, New Haven, Connecticut, USA. 10. Yale School of Public Health, New Haven, Connecticut, USA. 11. Indus Hospital, Karachi, Pakistan.
Abstract
BACKGROUND: Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. METHODS: The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. RESULTS: Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionamide, and 4.4 per 100 person-months with a fluoroquinolone and ethambutol. There were 53 (83%) grade 1 and 11 grade 2 AEs, with no grade 3 or 4 AEs. In multivariable analysis, the risk of AEs was higher in contacts prescribed ethionamide as compared to ethambutol adjusting for age, sex, and body mass index (adjusted hazard ratio, 2.1 [95% confidence interval {CI}, 1.2-3.6]). Overall, there was no notable difference in treatment completion among the contacts who experienced an AE and those who did not (crude odds ratio, 1.1 [95% CI, .52-2.5]). CONCLUSIONS: A fluoroquinolone-based preventive treatment regimen for drug-resistant TB exposure is well tolerated. Regimens with ethionamide are more likely to result in AEs.
BACKGROUND: Completion of tuberculosis (TB) preventive treatment is important to optimize efficacy; treatment-related adverse events (AEs) sometimes result in discontinuation. This study describes the occurrence of AEs and their risk factors during a 6-month, 2-drug, fluoroquinolone-based preventive treatment for household contacts of patients with drug-resistant TB in Karachi, Pakistan. METHODS: The primary outcome was development of any clinical AE during preventive treatment. Adverse events were categorized using the AE grading tables of the National Institutes of Health. Time-to-event analysis with Kaplan-Meier curves and Cox proportional hazards models accounting for recurrence were used to analyze associated risk factors. RESULTS: Of the 172 household contacts on preventive treatment, 36 (21%) developed 64 AEs during 813 months of treatment. The incidence of AEs over 6 months of treatment was 7.9 per 100 person-months; 16 per 100 person-months with a fluoroquinolone and ethionamide, and 4.4 per 100 person-months with a fluoroquinolone and ethambutol. There were 53 (83%) grade 1 and 11 grade 2 AEs, with no grade 3 or 4 AEs. In multivariable analysis, the risk of AEs was higher in contacts prescribed ethionamide as compared to ethambutol adjusting for age, sex, and body mass index (adjusted hazard ratio, 2.1 [95% confidence interval {CI}, 1.2-3.6]). Overall, there was no notable difference in treatment completion among the contacts who experienced an AE and those who did not (crude odds ratio, 1.1 [95% CI, .52-2.5]). CONCLUSIONS: A fluoroquinolone-based preventive treatment regimen for drug-resistant TB exposure is well tolerated. Regimens with ethionamide are more likely to result in AEs.
Authors: S Bamrah; R Brostrom; F Dorina; L Setik; R Song; L M Kawamura; A Heetderks; S Mase Journal: Int J Tuberc Lung Dis Date: 2014-08 Impact factor: 2.373
Authors: James A Seddon; Anneke C Hesseling; Heather Finlayson; Katherine Fielding; Helen Cox; Jennifer Hughes; Peter Godfrey-Faussett; H Simon Schaaf Journal: Clin Infect Dis Date: 2013-09-24 Impact factor: 9.079
Authors: Amyn A Malik; Neel R Gandhi; Timothy L Lash; Lisa M Cranmer; Saad B Omer; Junaid F Ahmed; Sara Siddiqui; Farhana Amanullah; Aamir J Khan; Salmaan Keshavjee; Hamidah Hussain; Mercedes C Becerra Journal: Emerg Infect Dis Date: 2021-03 Impact factor: 6.883