Time to Sputum Culture Conversion and the Intensive Phase Treatment Outcomes in South African Patients with Isoniazid Mono-resistant Tuberculosis
Main Article Content
Abstract
Background: Isoniazid mono-resistant tuberculosis defined by resistance to isoniazid while remaining susceptible to other first-line drugs, presents significant treatment challenges. This study aimed to determine the time to sputum culture conversion and assess the intensive phase treatment outcomes among Isoniazid mono-resistant tuberculosis patients in South Africa.
Conclusion: Isoniazid mono-resistant tuberculosis patients in this cohort experienced prolonged time to sputum culture conversion and a high proportion of unfavourable intensive phase treatment outcomes. Delayed sputum culture conversion was strongly associated with poor treatment outcomes, highlighting the critical role isoniazid plays in drug-resistant tuberculosis therapy. Consequently, there is need for intensified monitoring and targeted interventions to improve early culture conversion and treatment success during the intensive phase treatment.
Methods: This retrospective cohort study analysed 145 Isoniazid mono-resistant tuberculosis patients aged 18–65 years treated at Brewelskoof Hospital, Western Cape, South Africa, from 2009 to 2015. Demographic and clinical characteristics were obtained from the hospital’s tuberculosis registry. Data analyses used descriptive statistics, chi-square, analysis of variance, Kaplan–Meier survival, and Cox proportional hazards models to assess the time to sputum culture conversion and the intensive phase treatment outcomes, adjusting for relevant covariates. All statistical analyses were conducted using SAS 9.4 (SAS Institute, Cary, NC, USA).
Results: The median age of Isoniazid mono-resistant tuberculosis patients was 37 years, with an interquartile range (IQR) of 30–44, with 76 (52.41%) being males. After six months of treatment, 71 patients (48.97%) achieved sputum culture conversion, while 74 (51.03%) did not. The overall median time to sputum culture conversion was 55 days (IQR: 25–91), with significant variation across age groups (p=0.0074). The shortest time to sputum culture conversion was observed among patients aged 50–59 years (33.71±7.89 days). Overall, most Isoniazid mono-resistant tuberculosis patients (72.41%, 95%CI: 64.63–79.04) experienced unfavourable intensive phase treatment outcomes. Patients with unfavourable outcomes were 79% more likely to have delayed sputum culture conversion compared to those with favourable outcomes (HRR: 1.79, 95% CI: 1.07–2.98, p=0.0264). Conversely, patients who were 50-59 years were 4 times at risk of early conversion compared to individuals <20 years of age (HRR: 4.19, 95% CI: 1.13–15.61, p=0.0327).
Conclusion: Isoniazid mono-resistant tuberculosis patients in this cohort experienced prolonged time to sputum culture conversion and a high proportion of unfavourable intensive phase treatment outcomes. Delayed sputum culture conversion was strongly associated with poor treatment outcomes, highlighting the critical role isoniazid plays in drug-resistant tuberculosis therapy. Consequently, there is need for intensified monitoring and targeted interventions to improve early culture conversion and treatment success during the intensive phase treatment.
Keywords:
Isoniazid mono-resistant tuberculosis, time to sputum culture conversion, intensive phase treatment outcome, South Africa
Article Details
How to Cite
OKONJI, Osaretin Christabel; MUGABO, Pierre; MGBERE, Osaro.
Time to Sputum Culture Conversion and the Intensive Phase Treatment Outcomes in South African Patients with Isoniazid Mono-resistant Tuberculosis.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7138>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7138.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Hoopes AJ, Kammerer JS, Harrington TA, et al. Isoniazid-Monoresistant Tuberculosis in the United States, 1993 to 2003. Archives of Internal Medicine 2008; 168: 1984–1992.
3. WHO W. WHO, 2008, https://www.who.int/publications/i/item/9789241563611 (2008, accessed 14 September 2024).
4. National Institute for communicable diseases, South African Tuberculosis Drug Resistance Survey 2012–14’ (2018). Available at: https://www.nicd.ac.za/assets/files/K-12750%20NICD%20National%20Survey%20Report_Dev_V11-LR.pdf (Accessed: 4 January 2025).
5. Cattamanchi A, Dantes RB, Metcalfe JZ, et al. Clinical Characteristics and Treatment Outcomes of Patients with Isoniazid-Monoresistant Tuberculosis. Clinical Infectious Diseases 2009; 48: 179–185.
6. Bang D, Andersen PH, Andersen ÅB, et al. Isoniazid-resistant tuberculosis in Denmark: Mutations, transmission and treatment outcome. Journal of Infection 2010; 60: 452–457.
7. Chien J-Y, Chen Y-T, Wu S-G, et al. Treatment outcome of patients with isoniazid mono-resistant tuberculosis. Clin Microbiol Infect 2015; 21: 59–68.
8. Menzies D, Benedetti A, Paydar A, et al. Standardized Treatment of Active Tuberculosis in Patients with Previous Treatment and/or with Mono-resistance to Isoniazid: A Systematic Review and Meta-analysis. PLoS Med 2009; 6: e1000150.
9. Menzies D, Benedetti A, Paydar A, et al. Effect of Duration and Intermittency of Rifampin on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis. PLOS Medicine 2009; 6: e1000146.
10. Gegia M, Winters N, Benedetti A, et al. Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis. The Lancet Infectious Diseases 2017; 17: 223–234.
11. Jacobson KR, Theron D, Victor TC, et al. Treatment Outcomes of Isoniazid-Resistant Tuberculosis Patients, Western Cape Province, South Africa. Clin Infect Dis 2011; 53: 369–372.
12. Kurbatova EV, Gammino VM, Bayona J, et al. Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis. The International Journal of Tuberculosis and Lung Disease 2012; 16: 1335–1343.
13. Kurbatova EV, Cegielski JP, Lienhardt C, et al. Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies. The Lancet Respiratory Medicine 2015; 3: 201–209.
14. Holtz TH, Sternberg M, Kammerer S, et al. Time to Sputum Culture Conversion in Multidrug-Resistant Tuberculosis: Predictors and Relationship to Treatment Outcome. Ann Intern Med 2006; 144: 650–659.
15. Javaid A, Ahmad N, Afridi AK, et al. Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study. Am J Trop Med Hyg 2018; 98: 1629–1636.
16. Brust JCM, Gandhi NR, Carrara H, et al. High treatment failure and default rates for patients with multidrug-resistant tuberculosis in KwaZulu-Natal, South Africa, 2000–2003. The International Journal of Tuberculosis and Lung Disease 2010; 14: 413–419.
17. Gegia M, Cohen T, Kalandadze I, et al. Outcomes among tuberculosis patients with isoniazid resistance in Georgia, 2007–2009. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2012; 16: 812.
18. van der Heijden YF, Karim F, Mufamadi G, et al. Isoniazid mono-resistant tuberculosis is associated with poor treatment outcomes in Durban, South Africa. Int J Tuberc Lung Dis 2017; 21: 670–676.
19. Báez-Saldaña R, Delgado-Sánchez G, García-García L, et al. Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010. PLoS One 2016; 11: e0168955.
20. Stagg Hr, Mc L, Td M, et al. Isoniazid resistant tuberculosis- a cause for concern? The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 2017; 21: 129.
21. The National Department of Health; Essential Drugs Programme. Primary Healthcare Standard Treatment Guideline and Essential Medicine List. 8 th ed. South Africa: National Department of Health; 2024. Available from: https://www.health.gov.za/nhi-edp-stgs-eml/.
22. WHO. WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis, https://www.who.int/publications/i/item/9789241550079 (2018, accessed 25 October 2024).
23. Department of Health (DOH) South African tuberculosis treatment guidelines NDOH, 2014.https://www.tbonline.info/media/uploads/documents/national_tuberculosis management_guidelines_%282014%29.
24. World Health Organization. Definitions and reporting framework for tuberculosis – 2013 revision: updated December 2014 and January 2020. Geneva: World Health Organization, https://apps.who.int/iris/handle/10665/79199.
25. UWC-POPIA-Policy, 2021, https://www.uwc.ac.za/files/files/UWC-POPIA-Policy-approved-C202103.pdf (accessed 3 June 2024).
26. Prach LM, Pascopella L, Barry PM, et al. Rifampin monoresistant tuberculosis and HIV comorbidity in California, 1993-2008: a retrospective cohort study. AIDS 2013; 27: 2615–2622.
27. Iqbal Z, Khan MA, Aziz A, et al. Time for culture conversion and its associated factors in multidrug-resistant tuberculosis patients at a tertiary level hospital in Peshawar, Pakistan. Pak J Med Sci 2022; 38: 1009–1015.
28. Sculier D, Getahun H. World Health Organization. WHO policy on collaborative TB/HIV activities: guidelines for national programmes and other stakeholders. Geneva: World Health Organization; 2012. https://iris.who.int/server/api/core/bitstreams/d38d86fb-a877-471b-88a6-9f62fba35790/content. Geneva: World Health Organization, 2012.
29. Elliott E, Draper HR, Baitsiwe P, et al. Factors affecting treatment outcomes in drug-resistant tuberculosis cases in the Northern Cape, South Africa. Public Health Action 2014; 4: 201–203.
30. Narasimhan P, Wood J, MacIntyre CR, et al. Risk Factors for Tuberculosis. Pulmonary Medicine 2013; 2013: 828939.
31. Cegielski JP, Chan P-C, Lan Z, et al. Aminoglycosides and Capreomycin in the Treatment of Multidrug-resistant Tuberculosis: Individual Patient Data Meta-analysis of 12 030 Patients From 25 Countries, 2009–2016. Clinical Infectious Diseases 2021; 73: e3929–e3936.
32. Tierney DB, Franke MF, Becerra MC, et al. Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment. PLOS ONE 2014; 9: e108035.