{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:13:46Z","timestamp":1790662426294,"version":"4.1.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ethiopian Public Health Institute, Amhara Public Health Institute, and Addis Ababa University","award":["form of providing laboratory facilities and materials"],"award-info":[{"award-number":["form of providing laboratory facilities and materials"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nThe emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis<\/jats:italic> Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nA cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus<\/jats:italic> and MTBDRsl<\/jats:italic> assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nOf the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and\/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1<\/jats:italic> (S315T1) (20, 76.9%) and rpoB<\/jats:italic> (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1<\/jats:italic> gene, and the other had missing gyrA WT1<\/jats:italic>, gyrA WT3<\/jats:italic>, and rrs WT1<\/jats:italic> genes without any mutation.<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nThe detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0303460","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T17:25:09Z","timestamp":1715880309000},"page":"e0303460","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-7000","authenticated-orcid":true,"given":"Bazezew","family":"Yenew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abebaw","family":"Kebede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayinalem","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0166-682X","authenticated-orcid":true,"given":"Getu","family":"Diriba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zemedu","family":"Mehammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misikir","family":"Amare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biniyam","family":"Dagne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waganeh","family":"Sinshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephrem","family":"Tesfaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dereje","family":"Beyene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woldaregay Erku","family":"Abegaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"pone.0303460.ref001","first-page":"13","article-title":"History of tuberculosis","volume":"16","author":"TM Daniel","year":"1994","journal-title":"Tuberculosis: pathogenesis, protection, and control"},{"issue":"1","key":"pone.0303460.ref002","doi-asserted-by":"crossref","DOI":"10.4084\/mjhid.2013.070","article-title":"The biology of mycobacterium tuberculosis infection","volume":"5","author":"G Delogu","year":"2013","journal-title":"Mediterranean journal of hematology and infectious diseases"},{"key":"pone.0303460.ref003","unstructured":"World Health Organization. Global tuberculosis report 2021. Geneva, World Health Organization. 2021."},{"key":"pone.0303460.ref004","unstructured":"World Health Organization. Global tuberculosis report 2018. Geneva, World Health Organization. 2018."},{"key":"pone.0303460.ref005","unstructured":"World Health Organization. Global tuberculosis report 2022. Geneva, World Health Organization. 2022. Licence: CC BY-NC-SA 3.0 IGO."},{"key":"pone.0303460.ref006","volume-title":"The End TB Strategy: Global strategy and targets for tuberculosis prevention, care and control after 2015","author":"World Health Organization","year":"2015"},{"issue":"3","key":"pone.0303460.ref007","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cmi.2016.08.024","article-title":"Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases","volume":"23","author":"GJ Fox","year":"2017","journal-title":"Clinical Microbiology and Infection"},{"issue":"12","key":"pone.0303460.ref008","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/S1473-3099(18)30654-6","article-title":"Global burden of tuberculosis: where we are and what to do","volume":"18","author":"MP Grobusch","year":"2018","journal-title":"The Lancet Infectious Diseases"},{"key":"pone.0303460.ref009","volume-title":"Guidance for the surveillance of drug resistance in tuberculosis","author":"World Health Organization","year":"2020","edition":"6"},{"issue":"1","key":"pone.0303460.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12889-015-1933-9","article-title":"Prevalence and drug resistance profile of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients attending two public hospitals in East Gojjam zone, northwest Ethiopia","volume":"15","author":"K Adane","year":"2015","journal-title":"BMC public health"},{"issue":"1","key":"pone.0303460.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-019-3978-3","article-title":"Molecular detection of Mycobacterium tuberculosis sensitivity to rifampicin and isoniazid in South Gondar Zone, northwest Ethiopia","volume":"19","author":"A Alelign","year":"2019","journal-title":"BMC infectious diseases"},{"issue":"102","key":"pone.0303460.ref012","first-page":"2376","article-title":"Genotyping and drug resistance patterns of M. tuberculosis in Eastern Amhara Region, Ethiopia","volume":"2","author":"A Esmael","year":"2014","journal-title":"J Clin Diagn Res"},{"issue":"1","key":"pone.0303460.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-021-05961-8","article-title":"Phenotypic and genotypic drug sensitivity profiles of Mycobacterium tuberculosis infection and associated factors in northeastern Ethiopia","volume":"21","author":"F Gashaw","year":"2021","journal-title":"BMC Infectious Diseases"},{"key":"pone.0303460.ref014","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.2147\/IDR.S257086","article-title":"Antimicrobial Drug Therapy Problems Among Patients in the Outpatient Department of Ataye Hospital, Northeast Ethiopia","volume":"13","author":"H Kassahun","year":"2020","journal-title":"Infection and Drug Resistance"},{"issue":"2","key":"pone.0303460.ref015","doi-asserted-by":"crossref","first-page":"e0229040","DOI":"10.1371\/journal.pone.0229040","article-title":"The burden of pre-extensively and extensively drug-resistant tuberculosis among MDR-TB patients in the Amhara region, Ethiopia","volume":"15","author":"A Shibabaw","year":"2020","journal-title":"PloS one"},{"key":"pone.0303460.ref016","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jctube.2018.06.002","article-title":"Xpert MTB\/RIF assay for the diagnosis of Mycobacterium tuberculosis and Rifampicin resistance in high human immunodeficiency virus setting in gambella regional state, southwest ethiopia","volume":"12","author":"E Ejeta","year":"2018","journal-title":"Journal of clinical tuberculosis and other Mycobacterial diseases"},{"issue":"4","key":"pone.0303460.ref017","doi-asserted-by":"crossref","first-page":"e0231320","DOI":"10.1371\/journal.pone.0231320","article-title":"Genetic diversity and drug resistance pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in the Benishangul Gumuz region and its surroundings, Northwest Ethiopia","volume":"15","author":"TA Lobie","year":"2020","journal-title":"PloS one"},{"key":"pone.0303460.ref018","volume-title":"Global Laboratory Initiative Advancing TB Diagnosis.","author":"World Health Organization","year":"2014"},{"key":"pone.0303460.ref019","volume-title":"Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis","author":"World Health Organization","year":"2018"},{"key":"pone.0303460.ref020","unstructured":"GenoType MTBDR Plus, VER 2.0, Instructions for Use, IFU-304A-02, Hain Lifesciences GmbH, Germany. 2012."},{"key":"pone.0303460.ref021","unstructured":"GenoType MTBDRsl VER 2.0, Instructions for use, IFU-317A-02. Hain Lifescience, Nehren, Germany. 2015."},{"key":"pone.0303460.ref022","volume-title":"Interpretation and reporting guide for laboratory staff and clinicians","author":"Global Laboratory Initiative","year":"2018"},{"issue":"2","key":"pone.0303460.ref023","doi-asserted-by":"crossref","first-page":"e0193083","DOI":"10.1371\/journal.pone.0193083","article-title":"Molecular epidemiology and drug sensitivity pattern of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in and around Ambo Town, Central Ethiopia","volume":"13","author":"M Tilahun","year":"2018","journal-title":"PloS one"},{"issue":"1","key":"pone.0303460.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12889-015-1955-3","article-title":"Drug resistance patterns of Mycobacterium tuberculosis complex and associated factors among retreatment cases around Jimma, Southwest Ethiopia","volume":"15","author":"K Abdella","year":"2015","journal-title":"BMC public health"},{"key":"pone.0303460.ref025","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.2147\/IDR.S165088","article-title":"Phenotypic and genotypic drug sensitivity of Mycobacterium tuberculosis complex isolated from South Omo Zone, Southern Ethiopia","volume":"11","author":"B Wondale","year":"2018","journal-title":"Infection and drug resistance"},{"issue":"6","key":"pone.0303460.ref026","doi-asserted-by":"crossref","first-page":"e0218545","DOI":"10.1371\/journal.pone.0218545","article-title":"Genetic diversity and drug susceptibility profiles of Mycobacterium tuberculosis obtained from Saint Peter\u2019s TB specialized Hospital, Ethiopia","volume":"14","author":"D Damena","year":"2019","journal-title":"PloS one"},{"issue":"3","key":"pone.0303460.ref027","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/jac\/dkp237","article-title":"Resistant mutants of Mycobacterium tuberculosis selected in vitro do not reflect the in vivo mechanism of isoniazid resistance","volume":"64","author":"IL Bergval","year":"2009","journal-title":"Journal of Antimicrobial Chemotherapy"},{"key":"pone.0303460.ref028","volume-title":"Guidelines for Clinical and Programmatic Management of TB, TB\/HIV, DR-TB and Leprosy in Ethiopia","author":"Federal Ministry of Health","year":"2021","edition":"7"},{"key":"pone.0303460.ref029","unstructured":"FMOH. Implementation guideline for TB\/HIV collaborative activities in Ethiopia. Addis Ababa: Federal Ministry of Health, 2008."},{"issue":"2","key":"pone.0303460.ref030","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijmyco.2016.02.009","article-title":"Drug resistance-conferring mutations in Mycobacterium tuberculosis from pulmonary tuberculosis patients in Southwest Ethiopia","volume":"5","author":"M Tadesse","year":"2016","journal-title":"International journal of mycobacteriology"},{"issue":"8","key":"pone.0303460.ref031","doi-asserted-by":"crossref","first-page":"e0236362","DOI":"10.1371\/journal.pone.0236362","article-title":"Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study","volume":"15","author":"LN Welekidan","year":"2020","journal-title":"PloS one"},{"key":"pone.0303460.ref032","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.2147\/IDR.S251151","article-title":"Inappropriate antibiotic use among inpatients attending Madda Walabu University Goba Referral Hospital, Southeast Ethiopia: implication for future use","author":"M Mama","year":"2020","journal-title":"Infection and Drug Resistance"},{"key":"pone.0303460.ref033","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ijid.2015.06.013","article-title":"Multidrug-resistant and heteroresistant Mycobacterium tuberculosis and associated gene mutations in Ethiopia","volume":"39","author":"D Mekonnen","year":"2015","journal-title":"International Journal of Infectious Diseases"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T17:25:49Z","timestamp":1715880349000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303460"}},"subtitle":[],"editor":[{"given":"Balew","family":"Arega Negatie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0303460","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,16]]}}}