Adverse Drug Reactions, Treatment Adherence and Treatment Outcomes in Drug-Resistant Tuberculosis Patients: a Single-center, Cross-sectional Study

Nadia Farhanah Syafhan, Galuh Zhafirah Rahmita, Sri Wulandah Fitriani

Abstract

Drug-Resistant Tuberculosis (DRTB) is a significant global health issue due to its rapid transmission and high morbidity. The variety of medications used in DRTB treatment increases the risk of adverse drug reactions (ADRs), which can contribute to patient non-adherence and adversely affect treatment outcomes. This study aimed to describe the occurrence of ADRs, quantify medication adherence rates, and assess treatment outcomes among patients with drug-resistant tuberculosis (DRTB). Furthermore, it sought to analyse the associations between ADRs, demographic and clinical variables, and medication adherence, as well as the associations between ADRs and treatment outcomes. Using a cross-sectional design, this study utilized medical records data and the Tuberculosis Information System (SITB) of adult DRTB patients treated at Universitas Indonesia Hospital from April 1, 2022, to February 28, 2023. A total sampling method was employed to select the research participants. Of the 65 patients, 60 (95.24%) experienced ADRs, and the Medication Refill Adherence method indicated an 89.23% adherence rate. During data collection period, two patients (3.08%) were classified as successful or cured. Chi-square tests revealed no significant relationship between ADRs and medication adherence (p = 0.373) or treatment outcomes (p = 0.120). All demographic and clinical factors (age, gender, comorbidities, treatment combinations, and potential drug interactions) also showed no significant relationships with adherence (p > 0.05), while treatment combinations showed significant relationships with treatment outcomes (p = 0.013). These findings highlight the importance of medicines optimisation strategies, including proactive ADR management and adherence support, to improve treatment outcomes in DRTB patients. 

Keywords

Adverse Drug Reactions; Drug-Resistant Tuberculosis; Medication Adherence; Treatment Outcome.

References

Alateah, S.M., Othman, M.W., Ahmed, M., Al Amro, M.S., Al Sherbini, N., Ajlan, H.H. (2020). A retrospective research of tuberculosis prevalence amongst patients attending a tertiary hospital in Riyadh, Saudi Arabia. J Clin Tuberc Other Mycobact Dis, 21:100185.

Ali, S., Khan, M.T., Khan, A.S., et al. (2020). Prevalence of multi-drug resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa–a high tuberculosis endemic area of Pakistan. Polish J Microbiol, 69(2):133-137.

Aminah, N.S., Djuwita, R. (2021). Trend dan Faktor yang Berhubungan dengan Keberhasilan Pengobatan Pasien TB MDR Paduan Short-term di Indonesia 2017-2019. Pro Heal J Ilm Kesehat, 3(1).

Ausi, Y., Santoso, P., Sunjaya, D.K., Barliana, M.I. (2021). Ausi, Y., Santoso, P., Sunjaya, D. K., & Barliana, M. I. (2021). Between Curing and Torturing: Burden of Adverse Reaction in Drug-Resistant Tuberculosis Therapy. Patient Preference and Adherence, 15, 2597–2607. https://doi.org/10.2147/PPA.S333111

Babu[ADM1] , L.P., Robin, N., Babu, J.V., Jose, J., George, S. (2021). Adverse Drug Reaction among Drug- Resistant Tuberculosis Treatnebt: an Observational Cohort Stdy. Int J Pharm abd Pharm Sci, 13(9).

Batte, C., Namusobya, M.S., Kirabo, R., Mukisa, J., Adakun, S., Katamba, A. (2021). Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda. Afr Health Sci, 21(1):238-247.

BPOM. (2020). Modul Farmakovigilans untuk Tenaga Profesional Kesehatan. Jakarta : BPOM RI

Chaokromthong[ADM2] , K., Sintao, N. (2021). Sample Size Estimation using Yamane and Cochran and Krejcie and Morgan and Green Formulas and Cohen Statistical Power Analysis by G* Power and Comparisions. Apheit Int J, 10(2):76-86.

Dela, A.I., Tank, N.D., Singh, A.P., Piparva, K.G. (2017). Adverse drug reactions and treatment outcome analysis of DOTS-plus therapy of MDR-TB patients at district tuberculosis centre: A four year retrospective research. Lung India Off Organ Indian Chest Soc, 34(6):522.

Dewi, L.V.I., Hakim, L., Sismindan, S., Ngatidjan, N., Putra, S.P. (2019). Gambaran Reaksi Obat Yang Tidak Dikehendaki pada Pengobatan Tuberkulosis di Puskesmas Kabupaten “X” Yogyakarta dan Hubungannya dengan Kepatuhan Minum Obat. Majalah Farmasetika, 4 (Suppl 1), 132 – 136

Foe-Essomba, J. R., Kenmoe, S., Tchatchouang, S., Ebogo-Belobo, J. T., Mbaga, D. S., Kengne-Ndé, C., Mahamat, G., Kame-Ngasse, G. I., Noura, E. A., Mbongue Mikangue, C. A., Feudjio, A. F., Taya-Fokou, J. B., Touangnou-Chamda, S. A., Nayang-Mundo, R. A., Nyebe, I., Magoudjou-Pekam, J. N., Yéngué, J. F., Djukouo, L. G., Demeni Emoh, C. P., Tazokong, H. R., … Eyangoh, S. (2021). Diabetes mellitus and tuberculosis, a systematic review and meta-analysis with sensitivity analysis for studies comparable for confounders. PloS one, 16(12), e0261246. https://doi.org/10.1371/journal.pone.0261246

Gler, M.T., Podewils, L.J., Munez, N., Galipot, M., Quelapio, M.I.D., Tupasi, T.E. (2012). Impact of patient and program factors on default during treatment of multidrug-resistant tuberculosis. Int J Tuberc lung Dis,16(7):955-960.

Hess, L,M,, Raebel, M,A., Conner, D.A., Malone, D.C. (2006). Measurement of adherence in pharmacy administrative databases: A proposal for standard definitions and preferred measures. Ann Pharmacother, 40(7-8):1280-1288.

Hussain, S., Banerjee, M., Tripathi, P., & Kumar, V. (2023). Immunometabolic pathways linking diabetes and TB: Emerging targets for host-directed therapy. Nature Reviews Endocrinology, 19(3), 189–203. https://doi.org/10.1038/s41574-023-00789-1

Ifayani O, Puspitasari IM, Insani WN, Pradipta IS. Efek Samping Obat Pada Pengobatan Tuberkulosis Resisten Obat. Maj Farm dan Farmakol. 2023;27(1):10-14.

Iweama, C. N., Agbaje, O. S., Umoke, P. C. I., Igbokwe, C. C., Ozoemena, E. L., Omaka-Amari, N. L., & Idache, B. M. (2021). Nonadherence to tuberculosis treatment and associated factors among patients using directly observed treatment short-course in north-west Nigeria: A cross-sectional research. SAGE open medicine, 9, 2050312121989497. https://doi.org/10.1177/2050312121989497

Julaiha, S. (2015). Pengaruh Reaksi Obat Tidak Dikehendaki Terhadap Kepatuhan Berobat Pasien Tuberkulosis Paru Dewasa Kategori I Di RS Urip Sumoharjo Lampung. Skripsi. Universitas Indonesia

Kemenkes RI. (2018). TBC Cepat Menular. https://www.kemkes.go.id/article/view/18032700001/waspada-tbc-cepat- menular.html.

Kemenkes RI. (2019). Keputusan Menteri Kesehatan Republik Indonesia No HK.01.07 Menkes/755/2019 Tentang Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis. Jakarta : Kementrian Kesehatan Republik Indonesia

Kemenkes RI. (2020). Petunjuk Teknis Penatalaksanaan Tuberkulosis Resistan Obat Di Indonesia. Jakarta : Kementrian Kesehatan Republik Indonesia

Khan, I., Ahmad, N., Khan, S., et al. (2019). Evaluation of treatment outcomes and factors associated with unsuccessful outcomes in multidrug resistant tuberculosis patients in Baluchistan province of Pakistan. J Infect Public Health, 12(6):809-815.

Kumar, N. P., Krishnananthasivam, S., Banurekha, V. V., Nair, D., Babu, S., & Selvaraj, P. (2023). Immune profiling of diabetic TB patients reveals impaired Th1 responses and dysregulated innate immunity. Frontiers in Immunology, 14, 1147589. https://doi.org/10.3389/fimmu.2023.1147589

Kurniaty, L. (2017). Hubungan Kejadian Efek Samping Obat Dan Keberhasilan Pengobatan Tuberkulosis Paru Kategori I Di RSUP Persahabatan: Peran Pengawas Menelan Obat. Skripsi. Universitas Indonesia

Madan, J., Gupta, S., Verma, R., & Singh, A. (2022). Advanced glycation end-products and TB pathogenesis in diabetes: A molecular link. Journal of Molecular Medicine, 100(6), 821–830. https://doi.org/10.1007/s00109-022-02193-y

Merative Micromedex. (2023). Severity Classification of Drug Drug Interaction. Published online 2023. dynamedex.com

Moore[ADM3] , D.S., Kirkland, S. (2007). The Basic Practice of Statistics. Vol 2. New York : WH Freeman

Munir, M.S., Nawas, A., Soetoyo, D.K. (2010). Pengamatan pasien tuberkulosis paru dengan multidrug resistant (TB-MDR) di poliklinik paru RSUP Persahabatan. J Respir Indo, 30(2)

Nair, D., Velayutham, B., Kannan, T., et al. (2017). Predictors of unfavourable treatment outcome in patients with multidrug-resistant tuberculosis in India. Public Heal Action, 7(1):32-38.

NIH. (2022). National Institutes of Health. Published 2022. https://www.nih.gov/nih-style- guide/age

Osterberg[ADM4] , L., Blaschke, T. (2005). Adherence to medication. N Engl J Med, 353(5):487- 497.

Palleria, C., Di Paolo, A., Giofrè, C., et al. (2013). Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci Off J Isfahan Univ Med Sci, 18(7):601

Reyaan[ADM5] , I.B.M., Kuning, C., Adnyana, I.K. (2021) Studi Potensi Interaksi Obat Pada Resep Polifarmasi di Dua Apotek Kota Bandung. J Manaj dan Pelayanan Farm.11(3):145-152

RSUI. (2022). RSUI Resmi Membuka Layanan Tuberkulosis Resistensi Obat (DR TB). https://rs.ui.ac.id/umum/berita-artikel/berita/rsui-resmi-membuka-layanan- tuberkulosis-resistensi-obat-tb-ro.

Seniantara, I.K., Ivana, T., Adang, Y.G. (2018). Pengaruh efek samping OAT (obat anti tuberculosis) terhadap kepatuhan minum obat pada pasien TBC di puskesmas. J Keperawatan Suaka Insa, 3(2):1-12.

Tiberi, S., Utjesanovic, N., Galvin, J., Centis, R., D'Ambrosio, L., van den Boom, M., Zumla, A., & Migliori, G. B. (2022). Drug resistant TB - latest developments in epidemiology, diagnostics and management. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 124 Suppl 1, S20–S25. https://doi.org/10.1016/j.ijid.2022.03.026

World Health Organization. (2021). Tuberculosis Profile:Indonesia. https://worldhealthorg.shinyapps.io/tb_profiles/

World Health Organization. (2022). Global Tuberkulosis Report 2022. https://www.who.int/teams/global- tuberculosis-programme/tb-reports/global-tuberculosis-report-2022

World Health Organization. (2025). Operational handbook on tuberculosis and comorbidities: Module 6. Geneva: World Health Organization. https://iris.who.int/bitstream/handle/10665/380063/9789240103276-eng.pdf?sequence=1

Wibowo, A., Burhan, E., Putra, A.C. (2021). Pola Resistansi Kuman Tuberkulosis dan Regimen Pengobatan Pada Pasien Tuberkulosis Resisten Obat Di Rumah Sakit Pusat Rujukan Respirasi Nasional Persahabatan Jakarta. J Kedokt Univ Lampung, 5(1):1-6

Wu, X., Yang, J., Tan, G., et al. (2019). Drug resistance characteristics of Mycobacterium tuberculosis isolates from patients with tuberculosis to 12 antituberculous drugs in China. Front Cell Infect Microbiol, 9:345.

DOI: https://doi.org/10.20961/jpscr.v10i2.87515

Refbacks

  • There are currently no refbacks.