Análise epidemiológica, microbiológica e molecular das infecções de corrente sanguínea adquiridas em ambiente hospitalar em estudo multicêntrico - Projeto SCOPE Brasil
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Data
2018-03-29
Autores
Doi, Andre Mario [UNIFESP]
Orientadores
Pignatari, Antonio Carlos Campos [UNIFESP]
Tipo
Tese de doutorado
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INTRODUÇÃO: As infecções da corrente sanguínea (ICS) estão entre as infecções mais comuns associadas aos cuidados de saúde (IRAS) e possuem alta morbidade e mortalidade. Estima-se que dois milhões de pacientes adquiram infecções relacionadas a assistência à saúde por ano nos Estados Unidos (CDC 2013). No Brasil, as infecções de corrente sanguínea também representam um dos principais agravos para pacientes com IRAS. De acordo com dados brasileiros (ANVISA 2016) cerca de 2.036 hospitais notificaram ICS relacionada a uso de cateter venoso central, representando cerca de 25.265 episódios de ICS primária durante o ano de 2015. OBJETIVO: O intuito do projeto SCOPE Brasil foi correlacionar dados epidemiológicos, microbiológicos e de resistência aos antimicrobianos do primeiro episódio de infecção hospitalar da corrente sanguínea de pacientes admitidos em hospitais das cinco regiões do Brasil (Norte, Nordeste, Sul, Sudeste e Centro-Oeste). MATERIAL E MÉTODOS: Entre 2007 e 2010 foram coletados dados epidemiológicos e microbiológicos de 16 centros médicos no Brasil e realizada análise fenotípica e molecular de resistência de isolados bacterianos e fúngicos provenientes de 2453 episódios de ICS associadas à assistência à saúde. RESULTADOS: A distribuição do sexo e idade foi homogênea dentre os pacientes incluídos no estudo frente aos diversos agentes causadores de ICS. As taxas de internação em UTI foram maiores para os BGNNF e para os SCoN. As infecções por bactérias do grupo CESP, Enterococcus spp, Pseudomonas aeruginosa e Acinetobacter spp apresentaram maiores taxas de mortalidade geral em 30 dias (variação de 48,4% a 60,3%). As ICS por Candida apresentaram a maior taxa de mortalidade geral, 72%. A presença de cateter venoso central foi o fator de risco mais encontrado para todos os agentes e a doença de base mais comum neoplasias malignas/linfoma. As bacteremias primárias por CVC foram as mais frequentes. Os bacilos Gram-negativos foram mais prevalentes que os cocos Gram-positivos (60% vs 39%, respectivamente). Os S. aureus foram os agentes mais prevalentes (15,4%) seguido dos Staphylococcus coagulasenegativo (13,8%), Klebsiella spp (13,2%). e Acinetobacter spp (12,5%). Em relação às infecções causadas por S. aureus a mortalidade geral observada foi de 35% sendo maior nas ICS causadas por MRSA (45.3%). A resistência à oxacilina foi observada em 43,4% dos S. aureus e em 90% dos SCoN. O SCCmec tipo III foi o mais encontrado nas duas espécies sendo nos S. aureus também observada frequência dos tipos II e IV. Os Enterococcus spp. apresentaram taxas de resistência a vancomicina de 24%, presença do gene vanA detectada em todas as amostras. A espécie E. faecalis foi a mais
comumente encontrada nas ICS. Em relação aos bacilos Gram-negativos, cerca de 16% dos isolados de E. coli eram EsβL positivas sendo as β –lactamases dos tipos TEM e CTXM as mais importantes. Para a Klebsiella pneumoniae 56,3% eram EsβL positivas sendo que as mais prevalentes foram: TEM-1, SHV-1, SHV-11 e SHV-12, CTXM-15 e CTXM-9. Apenas dois isolados que presentavam resistência aos carbapenêmicos eram blaKPC positivos. Do grupo CESP, as espécies mais isoladas foram Enterobacter cloaceae, Serratia marcescens e Proteus mirabilis. Cerca de 27% apresentaram resistência às cefalosporinas de amplo espectro sendo que 74,1% destas foram positivas para os genes blaTEM, blaSHV e/ou blaCTX-M. Nas amostras resistentes aos carbapenêmicos não foram detectados os genes codificadores de carbapenemases. Dentre os BGNNF, os Acinetobacter spp e Pseudomonas spp. foram o 4o e 5o. agentes mais prevalentes. Cerca de 37% das Pseudomonas spp apresentaram resistência aos carbapenêmicos sendo a blaSPM a carbapenemase mais prevalente. Em relação aos Acinetobacter spp. as taxas de resistência aos carbapenêmicos foram de 60,7% sendo o gene blaOXA-23 o mais prevalente. Também avaliamos as ICS por Candida spp. observando uma elevada mortalidade nestas infecções (72%) com emergência de C. glabrata (10%). Elevadas taxas de sensibilidade às equinocandinas e anfotericina B foram observadas dentre todas as espécies. CONCLUSÃO: A distribuição do sexo e idade foi homogênea dentre os pacientes incluídos no estudo sendo as taxas de internação em UTI maiores para os BGNNF e para os SCoN. As infecções por bactérias do grupo CESP, Enterococcus spp, Pseudomonas aeruginosa e Acinetobacter spp apresentaram maiores taxas de mortalidade geral em 30 dias. As ICS por Candida apresentaram a maior taxa de mortalidade geral, 72%. A presença de cateter venoso central foi o fator de risco mais encontrado para todos os agentes e a doença de base mais comum neoplasias malignas/linfoma. Os S. aureus foram os agentes mais prevalentes seguido dos Staphylococcus coagulase-negativo Klebsiella spp e Acinetobacter spp. com mortalidade
geral em torno de 35%, maior nas ICS causadas por MRSA (45.3%). O SCCmec tipo III foi o mais encontrada em S aureus e SCoN. A taxa de resistência a vancomicina para Enterococos foi de 24%, com presença do gene vanA em 100% dos mesmos. Em relação aos bacilos Gram-negativos, cerca de 16% dos isolados de E. coli eram EsβL positivas sendo as β –lactamases dos tipos TEM e CTXM as mais importantes. Para a Klebsiella pneumoniae 56,3% eram EsβL positivas sendo que as mais prevalentes foram: TEM-1, SHV-1, SHV-11 e SHV-12, CTXM-15 e CTXM-9. Apenas dois isolados que presentavam resistência aos carbapenêmicos eram blaKPC positivos. No grupo CESP, as espécies mais isoladas foram Enterobacter cloaceae, Serratia marcescens e Proteus mirabilis. Cerca de 27% apresentaram resistência às cefalosporinas de amplo espectro sendo que 74,1% destas foram positivas para os genes blaTEM, blaSHV e/ou blaCTX-M. Nào foram ddetectados genes codificadores de carbapenemases. Dentre os BGNNF, os Acinetobacter spp e Pseudomonas spp. foram o 4o e 5o. agentes mais prevalentes. Cerca de 37% das Pseudomonas spp apresentaram resistência aos carbapenêmicos sendo a blaSPM a carbapenemase mais prevalente. A taxa de resistência aos carbapenêmicos para Acinetobacter spp. foi de 60,7% sendo o gene blaOXA-23 o mais prevalente. Para Candida spp. observamos uma elevada taxa de mortalidade (72%) com emergência de C. glabrata (10%). Elevadas taxas de sensibilidade às equinocandinas e anfotericina B foram observadas dentre todas as espécies.
INTRODUCTION: Bloodstream infections (BSI) are among the most common infections associated to healthcare assistance and have high morbidity and mortality rates. It is estimated that two million patients acquire HAI annually in United States (CDC 2013). In Brazil, bloodstream infections are one of the main problems for patients with HAI. According to Anvisa (brazilian health regulatory agency) in 2016, 2,036 hospitals reported BSI related to the use of a central venous catheter, representing about 25,265 episodes of primary ICS during the year of 2015. (ANVISA 2016). OBJECTIVE: The purpose of the SCOPE Brasil project was to associate epidemiological, microbiological and antimicrobial resistance profiles from the first episode of nosocomial BSI of patients admitted to hospitals in the five regions of Brazil (North, Northeast, South, Southeast and Central West). MATERIALS AND METHODS: Epidemiological and microbiological data were collected from 16 medical centers in Brazil and phenotypic and molecular resistance analyses were performed for bacterial and fungal isolates from 2453 episodes of nosocomial BSI. RESULTS: Gender and age distribution was homogeneous among the patients included in the study according to different agents. ICU admission was higher for BGNNF and SCoN. Bacterial infections caused by group CESP, Enterococcus spp, Pseudomonas spp and Acinetobacter spp showed higher overall mortality rates in 30 days (ranging from 48.4% to 60.3%). Candida presented the highest overall mortality rate, 72%. The presence of central venous catheter was the most common risk factor for all agents. Malignancies/Linfoma was the most common underlying condition. Central-line BSIs Primary were the most frequent source of infection. Gramnegative bacilli were more prevalent than Gram-positive cocci (60% vs 39%, respectively). S. aureus was the most prevalent agent (15.4%) followed by coagulase-negative Staphylococcus (13.8%), Klebsiella spp (13.2%). and Acinetobacter spp. (12.5%). The overall mortality for S. aureus was 35%,, higher in BSI caused by MRSA (45.3%). Resistance to oxacillin was observed in 43.4% of S. aureus and 90% of SCoN. The SCCmec type III was the most prevalent in both species. For S. aureus SCCmec types II and IV also were observed. The resistance rates for vancomycin in Enterococcus spp. was 24%, the presence of vanA gene was detected in all samples. The species E. faecalis was the most commonly found in the BSI. In relation to Gram-negative bacilli, 16% of the E. coli isolates were EsβL positive; the most important β-lactamases were TEM and CTXM. For Klebsiella pneumoniae, 56.3% were EsβL positive and the most prevalent β-lactamases were TEM-1, SHV-1, SHV-11 and SHV-12, CTXM-15 and CTXM-9. Only two isolates carbapenem resistants were blaKPC positive. From the CESP group, the most isolated species were Enterobacter cloaceae, Serratia marcescens and Proteus mirabilis. About 27% presented resistance to broadspectrum cephalosporins, and 74.1% of them were positive for blaTEM, blaSHV and / or blaCTX-M genes. In carbapenem-resistant samples, genes encoding carbapenemases gene were not detected. Among non-fermenters Gram-negative, Acinetobacter spp and Pseudomonas spp. were the 4th and 5th.most prevalent agents. About 37% of Pseudomonas spp presented resistance to carbapenems; blaSPM was the most prevalent carbapenemase gene. Acinetobacter spp resistance rates to carbapenems were 60.7% and the blaOXA-23 gene was the most prevalent. We also evaluated BSI caused by Candida spp. observing a high mortality rate in these infections (72%) with emergence of C. glabrata (10%). High sensitivity rates to echinocandins and amphotericin B were observed among all species. CONCLUSION: The SCOPE Brazil is one of the few national epidemiological studies to carry out an epidemiological, microbiological and resistance mechanisms characterization from nosocomial bloodstream infections. This data are importat corroborate empiral treatment based in epidemiological susceptibility profile and monitoring the dissemination and emergence of resistance mechanisms.
INTRODUCTION: Bloodstream infections (BSI) are among the most common infections associated to healthcare assistance and have high morbidity and mortality rates. It is estimated that two million patients acquire HAI annually in United States (CDC 2013). In Brazil, bloodstream infections are one of the main problems for patients with HAI. According to Anvisa (brazilian health regulatory agency) in 2016, 2,036 hospitals reported BSI related to the use of a central venous catheter, representing about 25,265 episodes of primary ICS during the year of 2015. (ANVISA 2016). OBJECTIVE: The purpose of the SCOPE Brasil project was to associate epidemiological, microbiological and antimicrobial resistance profiles from the first episode of nosocomial BSI of patients admitted to hospitals in the five regions of Brazil (North, Northeast, South, Southeast and Central West). MATERIALS AND METHODS: Epidemiological and microbiological data were collected from 16 medical centers in Brazil and phenotypic and molecular resistance analyses were performed for bacterial and fungal isolates from 2453 episodes of nosocomial BSI. RESULTS: Gender and age distribution was homogeneous among the patients included in the study according to different agents. ICU admission was higher for BGNNF and SCoN. Bacterial infections caused by group CESP, Enterococcus spp, Pseudomonas spp and Acinetobacter spp showed higher overall mortality rates in 30 days (ranging from 48.4% to 60.3%). Candida presented the highest overall mortality rate, 72%. The presence of central venous catheter was the most common risk factor for all agents. Malignancies/Linfoma was the most common underlying condition. Central-line BSIs Primary were the most frequent source of infection. Gramnegative bacilli were more prevalent than Gram-positive cocci (60% vs 39%, respectively). S. aureus was the most prevalent agent (15.4%) followed by coagulase-negative Staphylococcus (13.8%), Klebsiella spp (13.2%). and Acinetobacter spp. (12.5%). The overall mortality for S. aureus was 35%,, higher in BSI caused by MRSA (45.3%). Resistance to oxacillin was observed in 43.4% of S. aureus and 90% of SCoN. The SCCmec type III was the most prevalent in both species. For S. aureus SCCmec types II and IV also were observed. The resistance rates for vancomycin in Enterococcus spp. was 24%, the presence of vanA gene was detected in all samples. The species E. faecalis was the most commonly found in the BSI. In relation to Gram-negative bacilli, 16% of the E. coli isolates were EsβL positive; the most important β-lactamases were TEM and CTXM. For Klebsiella pneumoniae, 56.3% were EsβL positive and the most prevalent β-lactamases were TEM-1, SHV-1, SHV-11 and SHV-12, CTXM-15 and CTXM-9. Only two isolates carbapenem resistants were blaKPC positive. From the CESP group, the most isolated species were Enterobacter cloaceae, Serratia marcescens and Proteus mirabilis. About 27% presented resistance to broadspectrum cephalosporins, and 74.1% of them were positive for blaTEM, blaSHV and / or blaCTX-M genes. In carbapenem-resistant samples, genes encoding carbapenemases gene were not detected. Among non-fermenters Gram-negative, Acinetobacter spp and Pseudomonas spp. were the 4th and 5th.most prevalent agents. About 37% of Pseudomonas spp presented resistance to carbapenems; blaSPM was the most prevalent carbapenemase gene. Acinetobacter spp resistance rates to carbapenems were 60.7% and the blaOXA-23 gene was the most prevalent. We also evaluated BSI caused by Candida spp. observing a high mortality rate in these infections (72%) with emergence of C. glabrata (10%). High sensitivity rates to echinocandins and amphotericin B were observed among all species. CONCLUSION: The SCOPE Brazil is one of the few national epidemiological studies to carry out an epidemiological, microbiological and resistance mechanisms characterization from nosocomial bloodstream infections. This data are importat corroborate empiral treatment based in epidemiological susceptibility profile and monitoring the dissemination and emergence of resistance mechanisms.
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DOI, André Mario. Análise epidemiológica, microbiológica e molecular das infecções de corrente sanguínea adquiridas em ambiente hospitalar em estudo multicêntrico : projeto SCOPE Brasil. 2018. 155 f.. Tese (Doutorado em Medicina translacional) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018