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Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12710/19383
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dc.contributor.authorChesov, Elena-
dc.contributor.authorCiobanu, Nelly-
dc.contributor.authorChesov, Dumitru-
dc.contributor.authorLange, Christoph-
dc.contributor.authorHeyckendorf, Jan-
dc.contributor.authorMerker, Matthias-
dc.contributor.authorCrudu, Valeriu-
dc.date.accessioned2021-12-13T13:37:32Z-
dc.date.available2021-12-13T13:37:32Z-
dc.date.issued2021-
dc.identifier.citationCHESOV, Elena, CIOBANU, Nelly, CHESOV, Dumitru, LANGE, Christoph, HEYCKENDORF, Jan, et al. Rezistenţa Mycobacterium tuberculosis la Linezolid – mutaţii asociate și factori de risc: studiu transversal, retrospectiv, analytic = Linezolid resistance of Mycobacterium tuberculosis – associated mutations and risk factors: cross-sectional retrospective analytical study. In: Revista de Ştiinţe ale Sănătăţii din Moldova. 2021, vol. 26(1), pp. 43-56. ISSN 2345-1467.en_US
dc.identifier.issn2345-1467-
dc.identifier.urihttps://cercetare.usmf.md/sites/default/files/2021-11/MJHS%201%2826%29.pdf-
dc.identifier.urihttp://repository.usmf.md/handle/20.500.12710/19383-
dc.descriptionNicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, Chiril Draganiuc Phthisiopneumology Institute, Chisinau, Republic of Moldova, German Centre for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel- Riems, Clinical Infectious Diseases, Research Center Borstel, Borstel Germany, National and Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel Germany, Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany, Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany, Department of Medicine, Umeå University, Umeå, Sweden, Global TB Program, Baylor College of Medicine and Texas Children´s Hospital, Houston, TX, USAen_US
dc.description.abstractIntroducere. Linezolidul (LNZ) este unul dintre principalele medicamente utilizate în tratamentul tuberculozei multidrog- rezistente (TB-MDR). La moment determinantele genetice asociate cu rezistenţa la LNZ nu sunt pe deplin caracterizate. Scopul studiului a fost de a descrie mutaţiile asociate cu rezistenţa la LNZ prin aplicarea secvenţierii întregului genom (WGS) și evaluarea factorilor de risc asociaţi cu rezistenţa la LNZ pe un set de tulpini de Mycobacterium tuberculosis (MTB) izolate de la bolnavii de TB-MDR din Republica Moldova. Material și metode. A fost realizat un studiu retrospectiv transversal pe un set de tulpini de MTB preluate din biobanca Laboratorului Naţional de Referinţă în Microbiologia Tuberculozei (LNRM). Au fost identificate toate tulpinile MTB stocate în perioada 2017-2018, obţinute din sputa pacienţilor cu TB-MDR, care au administrat LNZ în schema de tratament pe parcursul ultimilor doi ani, indiferent de durata administrării LNZ. Au fost considerate eligibile pentru studiu doar tulpinile MTB izolate de la pacienţii cu o expunere cumulativă la LNZ mai mare de 30 de zile. Datele WGS ale tulpinilor de MTB incluse în studiu au fost comparate cu rezultatele testelor fenotipice de sensibilitate pe medii lichide pentru 3 concentraţii de LNZ (0,5 mg/L; 1,0 mg/L; 2,0 mg/L). Caracteristicile clinice ale pacienţilor din studiu au fost preluate din Registrul naţional electronic al bolnavilor cu TB (SIME-TB). Regresia logistică multiplă a fost efectuată pentru a determina factorii de risc pentru rezistenţa la LNZ. Rezultate. 52/74 (70,3%) tulpini MTB au fost incluse în studiu, dintre acestea 15 (28,8%) au fost fenotipic rezistente la LNZ, dintre care în cazul a 12/52 (23,1%) tulpini a fost găsită o corelarea genotipică cu rezistenţa la LNZ. În 8 cazuri au fost găsite mutaţii în gena rplC (460T>C). În alte 4 cazuri, au fost identificate mutaţii în gena rrl (2746G>A; 2814G>T; 2810A>C; 2270G>T). S-a determinat o asociere semnificativă între rezistenţa la LNZ și numărul de medicamente active din regimul de tratament TB-MDR (OR 0,23; 95%CI -0,03 - 0,70; p = 0,04). O asociere mai slabă s-a stabilit cu numărul de doze de LNZ administrate anterior (OR 1,01; 95%CI 1,004-1,03; p = 0,03). Concluzii. La majoritatea tulpinilor de MTB studiate, rezistenţa la LNZ a fost asociată cu mutaţii în genele rrl și rplC. Numărul insuficient de medicamente active în regimul de tratament al TB-MDR crește șansele de apariţie a rezistenţei la LNZ.en_US
dc.description.abstractIntroduction. Linezolid (LNZ) is one of the main drugs used for multidrug-resistant tuberculosis (MDR-TB) treatment. Genetic targets associated with resistance to LNZ are not fully characterized. The aim of the study was to describe mutations associated with LNZ resistance by applying whole genome sequencing (WGS) and to assess the risk factors for LNZ resistance in a set of M. tuberculosis clinical isolates from the Republic of Moldova. Material and methods. We conducted a retrospective cross-sectional study on a set of MTB isolates retrieved from the biobank of National Reference Laboratory for Tuberculosis Microbiology (NRLM). We identified all sputum culture isolates stored during 2017-2018, obtained from adult MDR-TB patients who had LNZ as part of their MDR-TB treatment at any time during two years before the collection corresponding sputum sample. Only isolates from patients with a cumulative exposure to LNZ longer than 30 days were considered eligible for the study. We performed WGS of the MTB strains and compared these results with liquid culture-based susceptibility tests on 3 concentrations of LNZ (0.5 mg/L; 1.0 mg/L; 2.0 mg/L). The clinical characteristics of the study patients were retrieved form the National TB Data Base (SIME-TB). The multiple regression analysis was performed to assess risk factors for LNZ resistance. Results. 52/74 (70,3%) isolates were included into the study of them 15 (28,8%) were phenotypically LNZ resistant. However only in 12/52 (23,1%) isolates genotypic correlates of LNZ resistant was found. In 8 cases mutations were detected in the rplC gene (460T>C). In other 4 cases the identified mutation implied rrl gene (2746G>A; 2814G>T; 2810A>C; 2270G>T). In a multivariate logistic regression model, significant association between LNZ resistance and the number of the active drugs in the MDR-TB treatment regimen (OR 0,23; 95%CI 0,03 – 0,70; p = 0,04) was found. A weaker association was found with the number of the previously taken LNZ doses (OR 1,01; 95%CI 1,004 – 1,03; p=0,03). Conclusions. In most of the studied MTB isolates LNZ resistance was associated with mutations in the rrl and rplC genes. A reduce number of the active drugs in the LNZ containing treatment regimen increase the chance of LNZ resistance emergence.en_US
dc.publisherRevista de Științe ale Sănătății din Moldova = Moldovan Journal of Health Sciencesen_US
dc.relation.ispartofRevista de Științe ale Sănătății din Moldova = Moldovan Journal of Health Sciencesen_US
dc.subjecttuberculosisen_US
dc.subjectWGSen_US
dc.subjectlinezolid resistanceen_US
dc.subjectrisk factorsen_US
dc.titleRezistenţa Mycobacterium tuberculosis la Linezolid – mutaţii asociate și factori de risc: studiu transversal, retrospectiv, analyticen_US
dc.title.alternativeLinezolid resistance of Mycobacterium tuberculosis – associated mutations and risk factors: cross-sectional retrospective analytical studyen_US
dc.typeArticleen_US
Appears in Collections:Revista de Științe ale Sănătății din Moldova : Moldovan Journal of Health Sciences 2021 nr. 1(26) ediție specială

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