Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: Dantas Júnior, Vicente Maciel
Orientador(a): Maia, Débora Castelo Branco de Souza Collares
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Link de acesso: http://repositorio.ufc.br/handle/riufc/77489
Resumo: The irrational use of antimicrobials and the global shortage of new drugs intensify the threat posed by superbugs, in addition to being an onerous, bureaucratic and prolonged process, which does not bring the financial return expected by large pharmaceutical companies. In this context, drug repositioning is a viable alternative for the treatment of infections of important clinical impact, such as those caused by Stenotrophomonas maltophilia, especially in pediatrics. Thus, the study aimed to observe the incidence of these infections and their outcomes in the last 5 years in a pediatric hospital in Ceará and repositioned fluoxetine to describe its antimicrobial and antibiofilm properties against this microorganism. The data on infections, clinical outcomes, topography of infections, age and gender of patients were followed through reports issued by the hospital's information technology systems and segregated year by year for later analysis. 10 strains isolated from hospital patients were selected and the antimicrobial activity of fluoxetine was tested in planktonic and biofilm. Fluoxetine was associated with antimicrobials used to treat S. maltophilia infections to assess improvement or interference in parameters. The same was done with drugs of known resistance to evaluate changes in the pattern and possible inhibition of these mechanisms. During the study period, 303 cases of infection by the pathogen were confirmed in 213 patients and 93 (43.66%) died due to alternative treatment, since the first line was out of the market. Fluoxetine showed antimicrobial activity alone but interacted negatively with the response of other drugs (trimethoprim/sulfamethoxazole, levofloxacin, meropenem, and gentamicin) when combined. High mortality rates observed coincided with findings in other publications and reiterated prolonged hospitalizations and immunocompromise due to COVID-19 as a substantial risk factor. More robust research is suggested regarding the possibility of using fluoxetine in antibacterial treatment and observation of its interaction at the molecular level with other drugs and consequently compromising typical response.
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spelling Dantas Júnior, Vicente MacielMaia, Débora Castelo Branco de Souza Collares2024-08-02T14:31:08Z2024-08-02T14:31:08Z2024DANTAS JÚNIOR, Vicente Maciel. Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará. 2024. 58 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77489. Acesso em: 02 ago. 2024.http://repositorio.ufc.br/handle/riufc/77489The irrational use of antimicrobials and the global shortage of new drugs intensify the threat posed by superbugs, in addition to being an onerous, bureaucratic and prolonged process, which does not bring the financial return expected by large pharmaceutical companies. In this context, drug repositioning is a viable alternative for the treatment of infections of important clinical impact, such as those caused by Stenotrophomonas maltophilia, especially in pediatrics. Thus, the study aimed to observe the incidence of these infections and their outcomes in the last 5 years in a pediatric hospital in Ceará and repositioned fluoxetine to describe its antimicrobial and antibiofilm properties against this microorganism. The data on infections, clinical outcomes, topography of infections, age and gender of patients were followed through reports issued by the hospital's information technology systems and segregated year by year for later analysis. 10 strains isolated from hospital patients were selected and the antimicrobial activity of fluoxetine was tested in planktonic and biofilm. Fluoxetine was associated with antimicrobials used to treat S. maltophilia infections to assess improvement or interference in parameters. The same was done with drugs of known resistance to evaluate changes in the pattern and possible inhibition of these mechanisms. During the study period, 303 cases of infection by the pathogen were confirmed in 213 patients and 93 (43.66%) died due to alternative treatment, since the first line was out of the market. Fluoxetine showed antimicrobial activity alone but interacted negatively with the response of other drugs (trimethoprim/sulfamethoxazole, levofloxacin, meropenem, and gentamicin) when combined. High mortality rates observed coincided with findings in other publications and reiterated prolonged hospitalizations and immunocompromise due to COVID-19 as a substantial risk factor. More robust research is suggested regarding the possibility of using fluoxetine in antibacterial treatment and observation of its interaction at the molecular level with other drugs and consequently compromising typical response.O uso irracional de antimicrobianos e a escassez global de novos medicamentos intensificam a ameaça representada pelas superbactérias além de ser um processo oneroso, burocrático e prolongado não traz retorno financeiro esperado pelas grandes indústrias farmacêuticas. Nesse contexto o reposicionamento de fármacos se apresenta como uma alternativa viável para tratamento de infecções de impacto clínico importante, como as causadas pelas Stenotrophomonas maltophilia, principalmente na pediatria. Com isso, o trabalho objetivou observar incidência dessas infecções e seus desfechos nos últimos 5 anos em um hospital pediátrico do Ceará e reposicionou fluoxetina para descrever suas propriedades antimicrobianas e antibiofilme frente a esse microrganismo. Os dados das infecções, desfechos clínicos, topografia das infecções, idade e gênero dos pacientes foram acompanhados através de relatórios emitidos por sistemas de tecnologia da informação do hospital e segregados ano a ano para posterior análise. 10 cepas isoladas em pacientes do hospital foram selecionadas e nelas se testou atividade antimicrobiana de fluoxetina de forma planctônica e em biofilme. Associou-se fluoxetina a antimicrobianos utilizados para tratar infecções por S. maltophilia para avaliar melhora ou interferência nos parâmetros. O mesmo foi feito com medicamentos de resistência conhecida para avaliar alteração do padrão e possível inibição desses mecanismos. No período estudado, 303 casos de infecção pelo patógeno foram confirmadas em 213 pacientes e 93 (43,66%) foram a óbito em vigência de tratamento alternativo já que a primeira linha estava fora do mercado. Fluoxetina apresentou atividade antimicrobiana isoladamente, porém interagiu negativamente na resposta dos outros medicamentos (sulfametoxazol/trimetoprima, levofloxaicno, meropenem e gentamicina) quando em associação. Altas taxas de mortalidade observadas coincidiram com os achados em outras publicações e reiteraram internações prolongadas e imunocomprometimento devido a covid-19 como um fator de risco substancial. Sugere-se pesquisas mais robustas quanto a possibilidade de utilizar fluoxetina no tratamento antibacteriano e observação de sua interação em nível molecular com outras drogas e consequentemente comprometer resposta típica.Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no CearáAntimicrobial and antibiofilm activity of fluoxetine against strains of Stenotrophomonas maltophilia isolated from patients from a pediatric hospital in Cearáinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisReposicionamento de MedicamentosFluoxetinaStenotrophomonas maltophiliaCovid-19PediatriaDrug RepurposingFluoxetineStenotrophomonas maltophiliaCOVID-19Pediatricsinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/7701845231751731https://orcid.org/0000-0002-6045-2354http://lattes.cnpq.br/2373473099684326LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/77489/6/license.txt8a4605be74aa9ea9d79846c1fba20a33MD56ORIGINAL2024_dis_vmdantasjunior.pdf2024_dis_vmdantasjunior.pdfapplication/pdf1292711http://repositorio.ufc.br/bitstream/riufc/77489/4/2024_dis_vmdantasjunior.pdf5705908e35c1e4bbcce727c64212cf7bMD54riufc/774892024-08-02 11:35:31.532oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-08-02T14:35:31Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
dc.title.en.pt_BR.fl_str_mv Antimicrobial and antibiofilm activity of fluoxetine against strains of Stenotrophomonas maltophilia isolated from patients from a pediatric hospital in Ceará
title Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
spellingShingle Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
Dantas Júnior, Vicente Maciel
Reposicionamento de Medicamentos
Fluoxetina
Stenotrophomonas maltophilia
Covid-19
Pediatria
Drug Repurposing
Fluoxetine
Stenotrophomonas maltophilia
COVID-19
Pediatrics
title_short Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
title_full Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
title_fullStr Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
title_full_unstemmed Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
title_sort Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará
author Dantas Júnior, Vicente Maciel
author_facet Dantas Júnior, Vicente Maciel
author_role author
dc.contributor.author.fl_str_mv Dantas Júnior, Vicente Maciel
dc.contributor.advisor1.fl_str_mv Maia, Débora Castelo Branco de Souza Collares
contributor_str_mv Maia, Débora Castelo Branco de Souza Collares
dc.subject.ptbr.pt_BR.fl_str_mv Reposicionamento de Medicamentos
Fluoxetina
Stenotrophomonas maltophilia
Covid-19
Pediatria
topic Reposicionamento de Medicamentos
Fluoxetina
Stenotrophomonas maltophilia
Covid-19
Pediatria
Drug Repurposing
Fluoxetine
Stenotrophomonas maltophilia
COVID-19
Pediatrics
dc.subject.en.pt_BR.fl_str_mv Drug Repurposing
Fluoxetine
Stenotrophomonas maltophilia
COVID-19
Pediatrics
description The irrational use of antimicrobials and the global shortage of new drugs intensify the threat posed by superbugs, in addition to being an onerous, bureaucratic and prolonged process, which does not bring the financial return expected by large pharmaceutical companies. In this context, drug repositioning is a viable alternative for the treatment of infections of important clinical impact, such as those caused by Stenotrophomonas maltophilia, especially in pediatrics. Thus, the study aimed to observe the incidence of these infections and their outcomes in the last 5 years in a pediatric hospital in Ceará and repositioned fluoxetine to describe its antimicrobial and antibiofilm properties against this microorganism. The data on infections, clinical outcomes, topography of infections, age and gender of patients were followed through reports issued by the hospital's information technology systems and segregated year by year for later analysis. 10 strains isolated from hospital patients were selected and the antimicrobial activity of fluoxetine was tested in planktonic and biofilm. Fluoxetine was associated with antimicrobials used to treat S. maltophilia infections to assess improvement or interference in parameters. The same was done with drugs of known resistance to evaluate changes in the pattern and possible inhibition of these mechanisms. During the study period, 303 cases of infection by the pathogen were confirmed in 213 patients and 93 (43.66%) died due to alternative treatment, since the first line was out of the market. Fluoxetine showed antimicrobial activity alone but interacted negatively with the response of other drugs (trimethoprim/sulfamethoxazole, levofloxacin, meropenem, and gentamicin) when combined. High mortality rates observed coincided with findings in other publications and reiterated prolonged hospitalizations and immunocompromise due to COVID-19 as a substantial risk factor. More robust research is suggested regarding the possibility of using fluoxetine in antibacterial treatment and observation of its interaction at the molecular level with other drugs and consequently compromising typical response.
publishDate 2024
dc.date.accessioned.fl_str_mv 2024-08-02T14:31:08Z
dc.date.available.fl_str_mv 2024-08-02T14:31:08Z
dc.date.issued.fl_str_mv 2024
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dc.identifier.citation.fl_str_mv DANTAS JÚNIOR, Vicente Maciel. Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará. 2024. 58 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77489. Acesso em: 02 ago. 2024.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/77489
identifier_str_mv DANTAS JÚNIOR, Vicente Maciel. Atividade antimicrobiana e antibiofilme da fluoxetina contra cepas de Stenotrophomonas maltophilia isoladas de pacientes de um hospital pediátrico no Ceará. 2024. 58 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77489. Acesso em: 02 ago. 2024.
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