{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:57:25Z","timestamp":1790391445953,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Linezolid (LZD) is a cornerstone of rifampicin-resistant tuberculosis (RR-TB) treatment, yet its hematological adverse events (AEs), particularly anemia, leukopenia, and thrombocytopenia, remain understudied in resource-limited settings like Uganda. With a high RR-TB burden and comorbidities such as HIV and malnutrition, understanding the prevalence and risk factors of these hematological AEs is critical to improving treatment adherence and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to determine the prevalence of hematological AEs and identify factors associated with hematological AEs among RR-TB patients receiving LZD-based regimens in Uganda.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>A multicenter retrospective cohort study was conducted using medical records of RR-TB patients treated with LZD at four Ugandan hospitals (Mbale RRH, Iganga General Hospital, Moroto RRH, and St. Kizito Matany Hospital) from 2020 to 2024. Hematological AEs were defined as anemia (Hb\u2009&lt;\u200912\u00a0g\/dL in women or &lt;\u200913\u00a0g\/dL in men), thrombocytopenia (platelets\u2009&lt;\u2009150\u2009\u00d7\u200910\u00b3\/\u00b5L), and leukopenia (WBC\u2009&lt;\u20093.7\u2009\u00d7\u200910\u2079\/L). Sociodemographic, clinical, and treatment-related data were extracted. A modified Poisson regression model with robust standard errors was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 412 patients, 62.9% (259\/412) had at least one hematological AE at baseline or during follow-up, and 36.4% (150\/412) had hematological AEs first detected after LZD initiation. Among patients with available baseline CBC, 40.0% (98\/245) developed incident hematological AEs. First detected anemia, thrombocytopenia, and leukopenia occurred in 21.4% (88\/412), 14.8% (61\/412), and 13.8% (57\/412) of patients, respectively. Rural residence (aPR 1.60, 95% CI 1.11\u20132.33) and divorced or widowed marital status (aPR 4.10, 95% CI 1.58\u201310.77) were independently associated with hematological AEs. Patients with hematological AEs had lower treatment success (83.0% vs. 93.5%) and higher loss to follow-up (15.1% vs. 5.9%) than those without AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hematological AEs were frequent among RR-TB patients receiving LZD in Uganda and were associated with reduced treatment success and increased loss to follow-up, while mortality remained low. Rural residence and divorced or widowed marital status were independently associated with these events, highlighting the need for targeted monitoring in higher-risk groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-026-13405-4","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:57:15Z","timestamp":1777571835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prevalence and factors associated with hematological adverse events in RR-TB patients on linezolid-based regimens in Uganda: a multicenter retrospective cohort study"],"prefix":"10.1186","volume":"26","author":[{"given":"Esther","family":"Apio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Baruch","family":"Baluku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Bwayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Peter","family":"Masaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erias","family":"Kirabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Kebesu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oreb","family":"Nankunda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Imalingat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Katuramu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"13405_CR1","unstructured":"World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-susceptible tuberculosis treatment. World Health Organization; 2022. 8\/11\/2024."},{"key":"13405_CR2","doi-asserted-by":"crossref","unstructured":"Viney K, Linh NN, Gegia M, Zignol M, Glaziou P, Ismail N, et al. New definitions of pre-extensively and extensively drug-resistant tuberculosis: update from the World Health Organization. Eur Respir J. 2021.","DOI":"10.1183\/13993003.congress-2021.OA1599"},{"key":"13405_CR3","unstructured":"World Health Organization. Fourth WHO consultation on the translation of tuberculosis research into global policy guidelines: meeting report, 15 February 2024. World Health Organization; 2024."},{"issue":"10","key":"13405_CR4","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1056\/NEJMoa1901814","volume":"382","author":"F Conradie","year":"2020","unstructured":"Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893\u2013902.","journal-title":"N Engl J Med"},{"issue":"2","key":"13405_CR5","doi-asserted-by":"publisher","first-page":"129","DOI":"10.4103\/ijmy.ijmy_57_21","volume":"10","author":"FM Dayyab","year":"2021","unstructured":"Dayyab FM, Iliyasu G, Ahmad BG, Habib AG. Early safety and efficacy of linezolid-based combination therapy among patients with drug-resistant tuberculosis in North-western Nigeria. Int J Mycobacteriology. 2021;10(2):129\u201335.","journal-title":"Int J Mycobacteriology"},{"issue":"6","key":"13405_CR6","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/ijpp.12543","volume":"27","author":"G Letswee","year":"2019","unstructured":"Letswee G, Kamau H, Gaida R, Truter I. Haematological adverse effects associated with linezolid in patients with drug-resistant tuberculosis: an exploratory study. Int J Pharm Pract. 2019;27(6):575\u20137.","journal-title":"Int J Pharm Pract"},{"key":"13405_CR7","unstructured":"WHO. WHO releases new global lists of high-burden countries for TB, HIV-associated TB and drug-resistant TB. 2021."},{"key":"13405_CR8","unstructured":"WHO. Global tuberculosis report 2025. 2025."},{"key":"13405_CR9","unstructured":"WHO. Tuberculosis profile: Uganda. World Health Organization; 2025."},{"key":"13405_CR10","unstructured":"World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022 update. World Health Organization; 2022."},{"key":"13405_CR11","unstructured":"World Health Organization. WHO consolidated operational handbook on tuberculosis. Module 4: treatment and care. World Health Organization; 2025."},{"issue":"5","key":"13405_CR12","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1056\/NEJMoa2400327","volume":"392","author":"L Guglielmetti","year":"2025","unstructured":"Guglielmetti L, Khan U, Vel\u00e1squez GE, Gouillou M, Abubakirov A, Baudin E, et al. Oral regimens for rifampin-resistant, fluoroquinolone-susceptible tuberculosis. N Engl J Med. 2025;392(5):468\u201382.","journal-title":"N Engl J Med"},{"issue":"3","key":"13405_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1080\/17512433.2023.2181160","volume":"16","author":"D Cattaneo","year":"2023","unstructured":"Cattaneo D, Marriott DJ, Gervasoni C. Hematological toxicities associated with linezolid therapy in adults: key findings and clinical considerations. Expert Rev Clin Pharmacol. 2023;16(3):219\u201330.","journal-title":"Expert Rev Clin Pharmacol"},{"key":"13405_CR14","doi-asserted-by":"crossref","unstructured":"Falzon D, Sch\u00fcnemann HJ, Harausz E, Gonz\u00e1lez-Angulo L, Lienhardt C, Jaramillo E, et al. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. Eur Respir J. 2017;49(3).","DOI":"10.1183\/13993003.02308-2016"},{"key":"13405_CR15","doi-asserted-by":"crossref","unstructured":"Cheng J, Yuan Y, Li J, Zhang R, Fan X, Xu Z, et al. Therapeutic drug monitoring of linezolid in drug-resistant tuberculosis patients: clinical factors and hematological toxicities. Infect Drug Resist. 2024:2531\u201340.","DOI":"10.2147\/IDR.S464429"},{"issue":"2","key":"13405_CR16","first-page":"72","volume":"57","author":"M Lakshminarasimhappa","year":"2022","unstructured":"Lakshminarasimhappa M. Web-based and smart mobile app for data collection: Kobo Toolbox\/Kobo collect. J Indian Libr Assoc. 2022;57(2):72\u20139.","journal-title":"J Indian Libr Assoc"},{"key":"13405_CR17","volume-title":"Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events, corrected version 2.1","author":"H Health UDo, Services","year":"2017","unstructured":"Health UDo, Services H. Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events, corrected version 2.1. editor US: National Institutes of Health.: National Institute of Allergy and Infectious Diseases DoA; 2017."},{"key":"13405_CR18","doi-asserted-by":"crossref","unstructured":"Oktaviani E, Anggadiredja K, Amalia L. Adverse drug reaction to linezolid in drug-resistant tuberculosis: a systematic review. Med Sci (Basel). 2025;14(1).","DOI":"10.3390\/medsci14010003"},{"key":"13405_CR19","doi-asserted-by":"publisher","first-page":"732503","DOI":"10.3389\/fphar.2021.732503","volume":"12","author":"J Fang","year":"2021","unstructured":"Fang J, Zhang X-S, Zhang C-H, Zhou Z-Y, Han L, Wang Y-X, et al. Model based identification of linezolid exposure\u2013toxicity thresholds in hospitalized patients. Front Pharmacol. 2021;12:732503.","journal-title":"Front Pharmacol"},{"issue":"4","key":"13405_CR20","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1515\/jbcpp-2020-0468","volume":"32","author":"NYI Pratama","year":"2021","unstructured":"Pratama NYI, Zulkarnain BS, Soedarsono, Fatmawati U. Hematological side effect analysis of linezolid in MDR-TB patients with individual therapy. J Basic Clin Physiol Pharmacol. 2021;32(4):777\u201381.","journal-title":"J Basic Clin Physiol Pharmacol"},{"issue":"3","key":"13405_CR21","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1111\/jcpt.13359","volume":"46","author":"Y Dai","year":"2021","unstructured":"Dai Y, Jiang S, Chen X, Han L, Zhang C, Yu X, et al. Analysis of the risk factors of linezolid-related haematological toxicity in Chinese patients. J Clin Pharm Ther. 2021;46(3):807\u201313.","journal-title":"J Clin Pharm Ther"},{"issue":"1","key":"13405_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12939-025-02437-y","volume":"24","author":"T Nalugwa","year":"2025","unstructured":"Nalugwa T, Annerstedt KS, Nabwire S, West NS, Kadota JL, Atkins S, et al. Identifying mechanisms by which social determinants of health impact TB diagnostic evaluation uptake in Uganda: a qualitative study. Int J Equity Health. 2025;24(1):1\u201310.","journal-title":"Int J Equity Health"},{"issue":"8","key":"13405_CR23","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.jiac.2016.05.003","volume":"22","author":"Y Hanai","year":"2016","unstructured":"Hanai Y, Matsuo K, Ogawa M, Higashi A, Kimura I, Hirayama S, et al. A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia. J Infect Chemother. 2016;22(8):536\u201342.","journal-title":"J Infect Chemother"},{"key":"13405_CR24","doi-asserted-by":"crossref","unstructured":"Barreto-Duarte B, Villalva-Serra K, Miguez-Pinto JP, Ara\u00fajo-Pereira M, Campos VM, Ferreira IB et al. Interplay between biological & social vulnerability and poor tuberculosis treatment outcome in Brazil: a nationwide study using multivariate modelling with excess risk. Lancet Reg Health Am. 2026;53.","DOI":"10.1016\/j.lana.2025.101305"},{"issue":"1","key":"13405_CR25","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13287-024-03731-2","volume":"15","author":"HS Park","year":"2024","unstructured":"Park HS, Lee B-C, Chae D-H, Yu A, Park JH, Heo J, et al. Cigarette smoke impairs the hematopoietic supportive property of mesenchymal stem cells via the production of reactive oxygen species and NLRP3 activation. Stem Cell Res Ther. 2024;15(1):145.","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"13405_CR26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12961-019-0428-z","volume":"17","author":"FC Mukumbang","year":"2019","unstructured":"Mukumbang FC, Orth Z, van Wyk B. What do the implementation outcome variables tell us about the scaling-up of the antiretroviral treatment adherence clubs in South Africa? A document review. Health Res Policy Syst. 2019;17(1):28.","journal-title":"Health Res Policy Syst"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-026-13405-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-026-13405-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-026-13405-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:48:05Z","timestamp":1782172085000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12879-026-13405-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["13405"],"URL":"https:\/\/doi.org\/10.1186\/s12879-026-13405-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7220294\/v1","asserted-by":"object"}]},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"26 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Mbale Regional Referral Hospital Research and Ethics Committee (Reference Number MRRH-2024-497) approved the study. The same committee provided a waiver of consent for the use of the data. The study was conducted in accordance with the ethical standards of the institutional research committee and with the 2013 revision of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and informed consent"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1176"}}