Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil

Detalhes bibliográficos
Autor(a) principal: Rocha, Verônica França Diniz
Data de Publicação: 2022
Outros Autores: Barbosa, Matheus Sales, Leal, Helena Ferreira, Silva, Giulyana Evelyn Oliveira, Sales, Nabila Monalisa Mendes Dantas, Monteiro, Adriano de Souza Santos, Azevedo, Jailton, Malheiros, Allan Roberto Xavier, Ataide, Ledilce Almeida, Moreira, Beatriz Meurer, Reis, Mitermayer Galvão, Bahia, Fabianna Márcia Maranhão, Reis, Joice Neves
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/57275
Resumo: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Instituto Nacional de Pesquisa em Resistência Antimicrobiana (Brasil). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RS (FAPERGS).
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spelling Rocha, Verônica França DinizBarbosa, Matheus SalesLeal, Helena FerreiraSilva, Giulyana Evelyn OliveiraSales, Nabila Monalisa Mendes DantasMonteiro, Adriano de Souza SantosAzevedo, JailtonMalheiros, Allan Roberto XavierAtaide, Ledilce AlmeidaMoreira, Beatriz MeurerReis, Mitermayer GalvãoBahia, Fabianna Márcia MaranhãoReis, Joice Neves2023-03-08T14:26:33Z2023-03-08T14:26:33Z2022ROCHA, Verônica França Diniz et al. Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil. Frontiers in Microbiology, v. 13, p. 1-12, 2022.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/5727510.3389/fmicb.2022.831770Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Instituto Nacional de Pesquisa em Resistência Antimicrobiana (Brasil). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RS (FAPERGS).Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.Secretaria da Saúde do Estado da Bahia. Salvador, BA, Brasil.Secretaria da Saúde do Estado da Bahia. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Yale School of Public Health. Yale University. New Haven, CT, United States.Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisas Gonçalo Moniz Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Multidrug-resistant gram-negative bacteria, such as carbapenem and colistin-resistant Klebsiella pneumoniae (ColR-CRKP), represent a major problem for health systems worldwide and have high lethality. This study investigated the genetic relationship, antimicrobial susceptibility profile, and resistance mechanisms to ColR-CRKP isolates from patients infected/colonized in a tertiary hospital in Salvador, Bahia/Brazil. From September 2016 to January 2018, 46 patients (56 ColR-CRKP positive cultures) were enrolled in the investigation but clinical and demographic data were obtained from 31 patients. Most of them were men (67.7%) and elderly (median age of 62 years old), and the median Charlson score was 3. The main comorbidities were systemic arterial hypertension (38.7%), diabetes (32.2%), and cerebrovascular disease (25.8%). The average hospitalization stay until ColR-CRKP identification in days were 35.12. A total of 90.6% used mechanical ventilation and 93.7% used a central venous catheter. Of the 31 patients who had the data evaluated, 12 had ColR-CRKP infection, and seven died (58.4%). Previous use of polymyxins was identified in 32.2% of the cases, and carbapenems were identified in 70.9%. The minimum inhibitory concentration (MIC) for colistin was > 16 μg/mL, with more than half of the isolates (55%) having a MIC of 256 μg/mL. The bla KPC gene was detected in 94.7% of the isolates, bla NDM in 16.0%, and bla GES in 1.7%. The bla OXA-48, bla VIM, and bla IMP genes were not detected. The mcr-1 test was negative in all 56 isolates. Alteration of the mgrB gene was detected in 87.5% (n = 49/56) of the isolates, and of these, 49.0% (24/49) had alteration in size probably due to IS903B, 22.4% (11/49) did not have the mgrB gene detected, 20.4% (10/49) presented the IS903B, 6.1% (3/49) had a premature stop codon (Q30*), and 2.1% (1/49) presented a thymine deletion at position 104 - 104delT (F35fs). The PFGE profile showed a monoclonal profile in 84.7% of the isolates in different hospital sectors, with ST11 (CC-258) being the most frequent sequence type. This study presents a prolonged outbreak of ColR-CRKP in which 83.9% of the isolates belonged to the same cluster, and 67.6% of the patients evaluated had not used polymyxin, suggesting the possibility of cross-transmission of ColR-CRKP isolates.engFrontiers MediaKlebsiella pneumoniaeResistente à colistinaResistente a carbapenemBactérias gram-negativas multirresistentesSurtoInfecção por enterobactériasKlebsiella pneumoniaeColistin-resistantCarbapenem-resistantMultidrug resistant gram-negative bacteriaOutbreakEnterobacterales infectionKlebsiella pneumoniaeResistência a medicamentosColistinaBactérias gram-negativasSurtos de doençasInfecçõesProlonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/57275/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALRocha, V.F.D. Prolonged Outbreak...2022.pdfRocha, V.F.D. Prolonged Outbreak...2022.pdfapplication/pdf1772395https://www.arca.fiocruz.br/bitstream/icict/57275/2/Rocha%2c%20V.F.D.%20Prolonged%20Outbreak...2022.pdf5fb452ab6548a9b0b998ba2c811a14a9MD52icict/572752023-03-15 14:32:52.965oai:www.arca.fiocruz.br:icict/57275Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:32:52Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
title Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
spellingShingle Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
Rocha, Verônica França Diniz
Klebsiella pneumoniae
Resistente à colistina
Resistente a carbapenem
Bactérias gram-negativas multirresistentes
Surto
Infecção por enterobactérias
Klebsiella pneumoniae
Colistin-resistant
Carbapenem-resistant
Multidrug resistant gram-negative bacteria
Outbreak
Enterobacterales infection
Klebsiella pneumoniae
Resistência a medicamentos
Colistina
Bactérias gram-negativas
Surtos de doenças
Infecções
title_short Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
title_full Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
title_fullStr Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
title_full_unstemmed Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
title_sort Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil
author Rocha, Verônica França Diniz
author_facet Rocha, Verônica França Diniz
Barbosa, Matheus Sales
Leal, Helena Ferreira
Silva, Giulyana Evelyn Oliveira
Sales, Nabila Monalisa Mendes Dantas
Monteiro, Adriano de Souza Santos
Azevedo, Jailton
Malheiros, Allan Roberto Xavier
Ataide, Ledilce Almeida
Moreira, Beatriz Meurer
Reis, Mitermayer Galvão
Bahia, Fabianna Márcia Maranhão
Reis, Joice Neves
author_role author
author2 Barbosa, Matheus Sales
Leal, Helena Ferreira
Silva, Giulyana Evelyn Oliveira
Sales, Nabila Monalisa Mendes Dantas
Monteiro, Adriano de Souza Santos
Azevedo, Jailton
Malheiros, Allan Roberto Xavier
Ataide, Ledilce Almeida
Moreira, Beatriz Meurer
Reis, Mitermayer Galvão
Bahia, Fabianna Márcia Maranhão
Reis, Joice Neves
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Rocha, Verônica França Diniz
Barbosa, Matheus Sales
Leal, Helena Ferreira
Silva, Giulyana Evelyn Oliveira
Sales, Nabila Monalisa Mendes Dantas
Monteiro, Adriano de Souza Santos
Azevedo, Jailton
Malheiros, Allan Roberto Xavier
Ataide, Ledilce Almeida
Moreira, Beatriz Meurer
Reis, Mitermayer Galvão
Bahia, Fabianna Márcia Maranhão
Reis, Joice Neves
dc.subject.other.en_US.fl_str_mv Klebsiella pneumoniae
Resistente à colistina
Resistente a carbapenem
Bactérias gram-negativas multirresistentes
Surto
Infecção por enterobactérias
topic Klebsiella pneumoniae
Resistente à colistina
Resistente a carbapenem
Bactérias gram-negativas multirresistentes
Surto
Infecção por enterobactérias
Klebsiella pneumoniae
Colistin-resistant
Carbapenem-resistant
Multidrug resistant gram-negative bacteria
Outbreak
Enterobacterales infection
Klebsiella pneumoniae
Resistência a medicamentos
Colistina
Bactérias gram-negativas
Surtos de doenças
Infecções
dc.subject.en.en_US.fl_str_mv Klebsiella pneumoniae
Colistin-resistant
Carbapenem-resistant
Multidrug resistant gram-negative bacteria
Outbreak
Enterobacterales infection
dc.subject.decs.en_US.fl_str_mv Klebsiella pneumoniae
Resistência a medicamentos
Colistina
Bactérias gram-negativas
Surtos de doenças
Infecções
description Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Instituto Nacional de Pesquisa em Resistência Antimicrobiana (Brasil). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RS (FAPERGS).
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-03-08T14:26:33Z
dc.date.available.fl_str_mv 2023-03-08T14:26:33Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv ROCHA, Verônica França Diniz et al. Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil. Frontiers in Microbiology, v. 13, p. 1-12, 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/57275
dc.identifier.issn.en_US.fl_str_mv 1664-302X
dc.identifier.doi.none.fl_str_mv 10.3389/fmicb.2022.831770
identifier_str_mv ROCHA, Verônica França Diniz et al. Prolonged outbreak of carbapenem and colistin-resistant klebsiella pneumoniae at a large tertiary hospital in Brazil. Frontiers in Microbiology, v. 13, p. 1-12, 2022.
1664-302X
10.3389/fmicb.2022.831770
url https://www.arca.fiocruz.br/handle/icict/57275
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/57275/1/license.txt
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