Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/21971 |
Resumo: | Bloodstream infections (BSI) are among the most frequent and serious infectious complications related to neonatal infections, responsible for high morbidity and mortality rates. Coagulase-negative staphylococci (CoNS) are the most isolated microorganisms, being Staphylococcus epidermidis the prevalent. CoNS have important virulence factors, such as biofilm formation and bacterial resistance, demonstrating the need for research on new drugs with antibacterial activity, or even drug repositioning. Triazenes (TZC) and statins are a promising alternative, due to significant biological activity. The objective of this study was to evaluate CoNS isolated from blood cultures of newborns (NB) admitted in the Hospital Universitário de Santa Maria (HUSM) in two years (2014, 2016/2017), and also the investigation of the in vitro synergistic antibacterial effect of statins and an inedited TZC compound {[1-(4-bromophenyl)-3-phenyltriazene N3-oxide-2 N1, O4](dimethylbenzylamine-2 C1, N4)palladium(II)} against standard American Type Culture Collection (ATCC) and ten CoNS (2014). CoNS were identified and had the susceptibility profile done through Vitek®2, and the minimum inhibitory concentration (MIC) of linezolid, tigecycline and vancomycin were determined by the broth microdilution method as well as the antibacterial activity of TZC and statins. Some clinical parameters of the newborns and the mortality rates were also evaluated. The biofilm production (2014) was verified through three phenotypic methodologies, in addition to the presence of icaACD genes. Isolates of S. epidermidis (2016/2017) were characterized in molecular epidemiology by whole genome sequencing (WGS). In 2014, of 131 NB, 176 CoNS were isolated; and in 2016/2017, 79 and 120, respectively, being S. epidermidis the prevalent in the Neonatal Intensive Care Unit (NICU). An increase in resistance indices was observed when compared the years 2014 and 2016/2017, especially to penicillin (71.26%, 99.17%) and oxacillin (76%, 84.17%). There was 100% susceptibility to linezolid, tigecycline and vancomycin. Regarding clinical significance, in 2014, 53.44% of the newborns were treated, and in 2016/2017, 78.48%, and the majority of cases were related to the use of a catheter. Regarding mortality rates, 15.71% of NB died in 2014 and 17.74% in 2016/2017. Regarding biofilm formation, 30.11% showed the icaACD genes concomitantly and 11.36% icaAC. Through congo red agar (CRA), adherence to the borosilicate tube (TM) and quantitative microplate technique (TCP), 42.04%, 38.64% and 40.91% of the isolates produced biofilm, respectively. When compared to the gold standard (presence of genes), CRA and TM presented low sensitivity and specificity. TCP had 99% sensitivity and 100% specificity; and it can be inferred that biofilm production is related to antimicrobial resistance. Of the isolates confirmed as S. epidermidis (2016/2017), 83.64% were resistant to methicillin (MRSE), most of them related to sequence type (ST) 2, associated with the staphylococcal chromosomal cassette mec (SCCmec) III and IVa. Regarding antibacterial activity, both ATCC strains and clinical isolates had MIC ≤ 528 μg/mL against TZC and statins, and the activity increased when TZC was associated with simvastatin, showing synergism (FICI ≤0.5). In this study, S. epidermidis was the prevalent, being associated with the use of catheter, and resistance rates increased over the years, evidencing the importance of intensifying control and prevention measures in this hospital. Still, CoNS were important pathogens in neonatal sepsis, responsible for significant mortality rates. In relation to biofilm production, CRA and TM showed low sensitivity and specificity when compared to the presence of the genes, whereas TCP, although a time-consuming technique, is a quantitative method that could be used to verify biofilm production in clinical isolates. In relation to antibacterial activity, TZC when associated with simvastatin demonstrated synergism. |
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Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazenoCoagulase-negative Staphylococci isolated of newborn blood cultures and synergistic antibacterial effect in vitro of statins with a triazene compoundStaphylococcus epidermidisSepse neontalSinvastatinaTriazenosAtorvastatinaNeonatal sepsisAtorvastatinSimvastatinTriazenesCNPQ::CIENCIAS DA SAUDE::FARMACIABloodstream infections (BSI) are among the most frequent and serious infectious complications related to neonatal infections, responsible for high morbidity and mortality rates. Coagulase-negative staphylococci (CoNS) are the most isolated microorganisms, being Staphylococcus epidermidis the prevalent. CoNS have important virulence factors, such as biofilm formation and bacterial resistance, demonstrating the need for research on new drugs with antibacterial activity, or even drug repositioning. Triazenes (TZC) and statins are a promising alternative, due to significant biological activity. The objective of this study was to evaluate CoNS isolated from blood cultures of newborns (NB) admitted in the Hospital Universitário de Santa Maria (HUSM) in two years (2014, 2016/2017), and also the investigation of the in vitro synergistic antibacterial effect of statins and an inedited TZC compound {[1-(4-bromophenyl)-3-phenyltriazene N3-oxide-2 N1, O4](dimethylbenzylamine-2 C1, N4)palladium(II)} against standard American Type Culture Collection (ATCC) and ten CoNS (2014). CoNS were identified and had the susceptibility profile done through Vitek®2, and the minimum inhibitory concentration (MIC) of linezolid, tigecycline and vancomycin were determined by the broth microdilution method as well as the antibacterial activity of TZC and statins. Some clinical parameters of the newborns and the mortality rates were also evaluated. The biofilm production (2014) was verified through three phenotypic methodologies, in addition to the presence of icaACD genes. Isolates of S. epidermidis (2016/2017) were characterized in molecular epidemiology by whole genome sequencing (WGS). In 2014, of 131 NB, 176 CoNS were isolated; and in 2016/2017, 79 and 120, respectively, being S. epidermidis the prevalent in the Neonatal Intensive Care Unit (NICU). An increase in resistance indices was observed when compared the years 2014 and 2016/2017, especially to penicillin (71.26%, 99.17%) and oxacillin (76%, 84.17%). There was 100% susceptibility to linezolid, tigecycline and vancomycin. Regarding clinical significance, in 2014, 53.44% of the newborns were treated, and in 2016/2017, 78.48%, and the majority of cases were related to the use of a catheter. Regarding mortality rates, 15.71% of NB died in 2014 and 17.74% in 2016/2017. Regarding biofilm formation, 30.11% showed the icaACD genes concomitantly and 11.36% icaAC. Through congo red agar (CRA), adherence to the borosilicate tube (TM) and quantitative microplate technique (TCP), 42.04%, 38.64% and 40.91% of the isolates produced biofilm, respectively. When compared to the gold standard (presence of genes), CRA and TM presented low sensitivity and specificity. TCP had 99% sensitivity and 100% specificity; and it can be inferred that biofilm production is related to antimicrobial resistance. Of the isolates confirmed as S. epidermidis (2016/2017), 83.64% were resistant to methicillin (MRSE), most of them related to sequence type (ST) 2, associated with the staphylococcal chromosomal cassette mec (SCCmec) III and IVa. Regarding antibacterial activity, both ATCC strains and clinical isolates had MIC ≤ 528 μg/mL against TZC and statins, and the activity increased when TZC was associated with simvastatin, showing synergism (FICI ≤0.5). In this study, S. epidermidis was the prevalent, being associated with the use of catheter, and resistance rates increased over the years, evidencing the importance of intensifying control and prevention measures in this hospital. Still, CoNS were important pathogens in neonatal sepsis, responsible for significant mortality rates. In relation to biofilm production, CRA and TM showed low sensitivity and specificity when compared to the presence of the genes, whereas TCP, although a time-consuming technique, is a quantitative method that could be used to verify biofilm production in clinical isolates. In relation to antibacterial activity, TZC when associated with simvastatin demonstrated synergism.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESInfecções de corrente sanguínea (ICS) estão entre as complicações infecciosas mais frequentes e graves relacionadas às infecções neonatais, responsáveis por elevadas taxas de morbimortalidade. Staphylococcus coagulase negativos (SCoN) são os microrganismos mais isolados, sendo Staphylococcus epidermidis o prevalente. SCoN apresentam importantes fatores de virulência, como a formação de biofilme e a resistência bacteriana, demonstrando a necessidade da pesquisa por novos fármacos com atividade antibacteriana, ou até mesmo o reposicionamento de drogas. Os triazenos (TZC) e as estatinas constituem uma alternativa promissora, devido a expressiva atividade biológica. O objetivo deste estudo foi avaliar SCoN isolados de hemoculturas de recém-nascidos (RN) admitidos no Hospital Universitário de Santa Maria (HUSM) no período de dois anos (2014; 2016/2017), além da investigação do efeito antibacteriano sinérgico in vitro de estatinas e de um composto TZC inédito, {[1-(4-bromofenil)-3-feniltriazenido N3-óxido-2 N1, O4](dimetilbenzilamina-2 C1, N4)paládio(II)} (Pd(dmba)LBr), frente cepas bacterianas padrão American Type Culture Collection (ATCC) e a dez SCoN (2014). Os SCoN foram identificados e tiveram o perfil de suscetibilidade realizados através do Vitek®2, e a concentração inibitória mínima (CIM) da linezolida, tigeciclina e vancomicina efetuadas pelo método da microdiluição em caldo; assim como a atividade antibacteriana do TZC e das estatinas. Também foram avaliados alguns parâmetros clínicos dos RN e as taxas de mortalidade. A produção de biofilme (2014) foi verificada através de três metodologias fenotípicas, além da presença dos genes icaACD. Isolados de S. epidermidis (2016/2017) foram caracterizados em nível de epidemiologia molecular pela sequenciação total do genoma (WGS). Em 2014, de 131 RN, foram isolados 176 SCoN; e em 2016/2017, 79 e 120, respectivamente, sendo S. epidermidis o prevalente, na Unidade de Terapia Intensiva Neonatal (UTI-RN). Observou-se um aumento nos índices de resistência quando comparados os anos de 2014 e 2016/2017, destacando-se os antimicrobianos penicilina (71,26%; 99,17%) e oxacilina (76%; 84,17%). Verificou-se 100% de suscetibilidade frente a linezolida, tigeciclina e vancomicina. Em relação à significância clínica, em 2014, 53,44% dos RN foram tratados, e em 2016/2017, 78,48%, sendo a maioria dos casos relacionada ao uso de cateter. Quanto às taxas de mortalidade, 15,71% dos RN foram a óbito em 2014 e 17,74% em 2016/2017. Em relação à formação de biofilme, 30,11% mostraram os genes icaACD concomitantemente e 11,36% icaAC. Através do ágar vermelho congo (CRA), aderência ao tubo de borossilicato (TM) e técnica quantitativa da microplaca (TCP), 42,04%, 38,64% e 40,91% dos isolados produziram biofilme, respectivamente. Quando comparados ao padrãoouro (presença dos genes), CRA e TM apresentaram baixa sensibilidade e especificidade. A TCP apresentou 99% de sensibilidade e 100% de especificidade; e pode-se inferir que a produção de biofilme está relacionada a resistência aos antimicrobianos. Dos isolados confirmados como S. epidermidis (2016/2017), 83,64% foram resistentes a meticilina (MRSE), estando a maioria relacionada ao sequence type (ST) 2, associados ao cassete cromossômico estafilocócico mec (SCCmec) III e a IVa. Em relação à atividade antibacteriana, tanto as cepas ATCC quanto os isolados clínicos apresentaram CIM ≤ 528 μg/mL frente ao TZC e as estatinas, sendo que a atividade aumentou quando o TZC foi associado à sinvastatina, mostrando sinergismo (FICI≤0,5). Neste estudo, S. epidermidis foi o prevalente, estando associado à utilização de cateter, sendo que as taxas de resistência aumentaram com o passar dos anos, evidenciando a importância de intensificar medidas de controle e prevenção neste hospital. Ainda, os SCoN foram importantes patógenos na sepse neonatal, responsáveis por significativas taxas de mortalidade. Em relação a produção de biofilme, CRA e TM demonstraram baixa sensibilidade e especificidade quando comparados a presença dos genes, já a TCP, apesar de ser uma técnica demorada, é um método quantitativo que poderia ser utilizado para verificar a produção de biofilme em isolados clínicos. Em relação a atividade antibacteriana, o TZC quando associado a sinvastatina demonstrou sinergismo.Universidade Federal de Santa MariaBrasilAnálises Clínicas e ToxicológicasUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeHorner, Rosmarihttp://lattes.cnpq.br/5907084134183708Motta, Amanda de Souza daRamos, Daniela FernandesMiragaia, MariaPicoli, Simone UlrichRampelotto, Roberta Filipini2021-08-17T17:19:07Z2021-08-17T17:19:07Z2019-08-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21971porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-18T06:03:15Zoai:repositorio.ufsm.br:1/21971Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-18T06:03:15Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno Coagulase-negative Staphylococci isolated of newborn blood cultures and synergistic antibacterial effect in vitro of statins with a triazene compound |
title |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
spellingShingle |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno Rampelotto, Roberta Filipini Staphylococcus epidermidis Sepse neontal Sinvastatina Triazenos Atorvastatina Neonatal sepsis Atorvastatin Simvastatin Triazenes CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
title_full |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
title_fullStr |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
title_full_unstemmed |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
title_sort |
Staphylococcus coagulase negativos isolados de hemoculturas de recém-nascidos e efeito antibacteriano sinérgico in vitro de estatinas com um composto triazeno |
author |
Rampelotto, Roberta Filipini |
author_facet |
Rampelotto, Roberta Filipini |
author_role |
author |
dc.contributor.none.fl_str_mv |
Horner, Rosmari http://lattes.cnpq.br/5907084134183708 Motta, Amanda de Souza da Ramos, Daniela Fernandes Miragaia, Maria Picoli, Simone Ulrich |
dc.contributor.author.fl_str_mv |
Rampelotto, Roberta Filipini |
dc.subject.por.fl_str_mv |
Staphylococcus epidermidis Sepse neontal Sinvastatina Triazenos Atorvastatina Neonatal sepsis Atorvastatin Simvastatin Triazenes CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Staphylococcus epidermidis Sepse neontal Sinvastatina Triazenos Atorvastatina Neonatal sepsis Atorvastatin Simvastatin Triazenes CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Bloodstream infections (BSI) are among the most frequent and serious infectious complications related to neonatal infections, responsible for high morbidity and mortality rates. Coagulase-negative staphylococci (CoNS) are the most isolated microorganisms, being Staphylococcus epidermidis the prevalent. CoNS have important virulence factors, such as biofilm formation and bacterial resistance, demonstrating the need for research on new drugs with antibacterial activity, or even drug repositioning. Triazenes (TZC) and statins are a promising alternative, due to significant biological activity. The objective of this study was to evaluate CoNS isolated from blood cultures of newborns (NB) admitted in the Hospital Universitário de Santa Maria (HUSM) in two years (2014, 2016/2017), and also the investigation of the in vitro synergistic antibacterial effect of statins and an inedited TZC compound {[1-(4-bromophenyl)-3-phenyltriazene N3-oxide-2 N1, O4](dimethylbenzylamine-2 C1, N4)palladium(II)} against standard American Type Culture Collection (ATCC) and ten CoNS (2014). CoNS were identified and had the susceptibility profile done through Vitek®2, and the minimum inhibitory concentration (MIC) of linezolid, tigecycline and vancomycin were determined by the broth microdilution method as well as the antibacterial activity of TZC and statins. Some clinical parameters of the newborns and the mortality rates were also evaluated. The biofilm production (2014) was verified through three phenotypic methodologies, in addition to the presence of icaACD genes. Isolates of S. epidermidis (2016/2017) were characterized in molecular epidemiology by whole genome sequencing (WGS). In 2014, of 131 NB, 176 CoNS were isolated; and in 2016/2017, 79 and 120, respectively, being S. epidermidis the prevalent in the Neonatal Intensive Care Unit (NICU). An increase in resistance indices was observed when compared the years 2014 and 2016/2017, especially to penicillin (71.26%, 99.17%) and oxacillin (76%, 84.17%). There was 100% susceptibility to linezolid, tigecycline and vancomycin. Regarding clinical significance, in 2014, 53.44% of the newborns were treated, and in 2016/2017, 78.48%, and the majority of cases were related to the use of a catheter. Regarding mortality rates, 15.71% of NB died in 2014 and 17.74% in 2016/2017. Regarding biofilm formation, 30.11% showed the icaACD genes concomitantly and 11.36% icaAC. Through congo red agar (CRA), adherence to the borosilicate tube (TM) and quantitative microplate technique (TCP), 42.04%, 38.64% and 40.91% of the isolates produced biofilm, respectively. When compared to the gold standard (presence of genes), CRA and TM presented low sensitivity and specificity. TCP had 99% sensitivity and 100% specificity; and it can be inferred that biofilm production is related to antimicrobial resistance. Of the isolates confirmed as S. epidermidis (2016/2017), 83.64% were resistant to methicillin (MRSE), most of them related to sequence type (ST) 2, associated with the staphylococcal chromosomal cassette mec (SCCmec) III and IVa. Regarding antibacterial activity, both ATCC strains and clinical isolates had MIC ≤ 528 μg/mL against TZC and statins, and the activity increased when TZC was associated with simvastatin, showing synergism (FICI ≤0.5). In this study, S. epidermidis was the prevalent, being associated with the use of catheter, and resistance rates increased over the years, evidencing the importance of intensifying control and prevention measures in this hospital. Still, CoNS were important pathogens in neonatal sepsis, responsible for significant mortality rates. In relation to biofilm production, CRA and TM showed low sensitivity and specificity when compared to the presence of the genes, whereas TCP, although a time-consuming technique, is a quantitative method that could be used to verify biofilm production in clinical isolates. In relation to antibacterial activity, TZC when associated with simvastatin demonstrated synergism. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-08-16 2021-08-17T17:19:07Z 2021-08-17T17:19:07Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21971 |
url |
http://repositorio.ufsm.br/handle/1/21971 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
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Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922139754201088 |