Staphylococcus aureus resistente à meticilina associado a serviços de saúde: patógeno persistente e ou epidemiologia em transição?
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2024-01-24
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Universidade Estadual Paulista (Unesp)
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Contextualização: O MRSA (do inglês, methicilin-resistant Staphylococcus aureus), resistente a quase todos os antimicrobianos beta-lactâmicos, é responsável por grande número de infecções de corrente sanguínea (ICS), com alta letalidade. Cepas de MRSA de diferentes linhagens não se restringem mais a seus ambientes de origem, com intercâmbio entre as de origem hospitalar, comunitária e animal. Nas décadas passadas, predominava como causa de ICS nosocomial o clone epidêmico brasileiro, que carreava em seu cromossomo o SSCmec tipo III (Staphylococcal chromosome cassette, type III), associado à resistência a múltiplas drogas, além dos beta-lactâmicos. Estudos recentes indicam a substituição desse clone por outros que carreiam SCCmec II ou IV. A suscetibilidade a antimicrobianos como
sulfametoxazol/trimetoprim (SMX/TMP), clindamicina e ciprofloxacino tem sido utilizada como indicador dessa substituição de clones. Objetivo: Identificar alterações epidemiológicas, clínicas e de resistência observadas em ICS por MRSA ao longo do tempo. Método: Nosso estudo foi realizado em duas etapas, ambas através da análise do banco de dados do Hospital das Clínicas da Faculdade de Medicina de
Botucatu, pertencente à Universidade Estadual Paulista. Na primeira etapa, ecológica, utilizamos estratégia de análise de séries temporais (Joinpoint Regression) para identificar alterações na tendência da resistência de ICS por MRSA a SMX/TMP, clindamicina e ciprofloxacino, no período de 2005 a 2019. Em um segundo estudo, utilizamos abordagem de base individual para casos de ICS MRSA diagnosticados
entre 2012 e 2021: uma análise tipo caso-caso, para identificar diferença nos preditores de ICS por MRSA suscetível versus resistente a SMX/TMP, seguida de um estudo de coorte de fatores associados a óbito em pacientes com ICS por MRSA. Resultados: No estudo ecológico, observamos uma queda abrupta da resistência a SMX/TMP a partir de 2008, com pequeno aumento após 2018. Essa tendência não foi
coincidente com aquelas da resistência a clindamicina e ciprofloxacino. No estudo caso-caso, observamos grande similaridade entre pacientes com HA-MRSA resistente ou suscetível a SMX/TMP, sendo os fatores diferenciais pouco relevantes. A mortalidade na coorte esteve associada ao foco pulmonar (HR=2,24; IC95%=1,40-3,57) e de pele/partes moles (HR=2,95, IC95%=1,44-6,07), índice de comorbidades
de Charlson (HR=1,15; IC95%=1,08-1,23), doença pulmonar (HR=1,64; IC95%=1,08-2,52) e presença de cateter venoso central (HR=2,08; IC95%=1,23-3,51); a antibioticoterapia apropriada foi associada a menor e mais tardia progressão para óbito (H=0,29; IC95%=0,18-0,48). Não houve impacto da pandemia de covid-19 sobre o prognóstico. Conclusão: Nossos estudos indicam uma mudança na distribuição
clonal do MRSA no HCFMB/UNESP, porém sem correspondência, entre o aumento da sensibilidade ao SMX/TMP e diminuição da mortalidade geral entre pacientes portadores de ICS por MRSA e ou por cepas de MRSA sensíveis ao SMX/TMP. Nossos dados estão de acordo com os relatos da literatura que indicam alta taxa de mortalidade entre os pacientes portadores de ICS por MRSA, sugerindo a
necessidade de implementação de melhorias nos cuidados de tais pacientes, através da otimização de medidas preventivas (de controle da disseminação do MRSA), diagnósticas (maior presunção) e, principalmente, instituição célere da terapia antimicrobiana adequada (anti-MRSA).
Context: Methicillin-resistant Staphylococcus aureus (MRSA), resistant to almost all beta-lactam antimicrobials, causes great number of bloodstream infections (BSIs), with high case-fatality ratios. MRSA strains of different lineages are no longer restricted to their environments of origins, with interchange occurring between thosen of hospital, community and animal origins. In past decades, the Brazilian epidemic clone predominated as the cause of nosocomial BSI, and it carried the SCCmec type III (Staphylococcal Chromosome Cassette, type III) in its chromosome, associated with resistance to multiple drugs in addition to beta-lactam. Recent studies indicate the replacement of this clone by others carrying SCCmec II or IV. Susceptibility to antimicrobials such as sulfamethoxazole/trimethoprim (SMX/TMP), clindamycin, and ciprofloxacin has been used as an indicator of this clone replacement. Objective: To identify epidemiological, clinical, and resistance changes observed in BSIs caused by MRSA over time. Method: Our study was conducted in two stages, both through the analysis of the database of the Hospital das Clínicas of the Botucatu Medical School, belonging to the São Paulo State University. In the first, ecological stage, we used a time-series analysis strategy (Joinpoint Regression) to identify changes in the trend of resistance in MRSA BSIs to SMX/TMP, clindamycin, and ciprofloxacin, in the period from 2005 to 2019. In a second study, we used an individual-based approach to BSIs cases diagnosed between 2012 and 2021: a case-case analysis to identify differences in predictors of BSI caused by MRSA susceptible versus resistant to SMX/TMP, followed by a cohort study of factors associated with death in patients with BSIs due to MRSA. Results: In the ecological study we observed an abrupt drop in resistance to SMX/TMP from 2008 onwards, with a slight increase after 2018. This trend was not coincident with those of resistance to clindamycin and ciprofloxacin. In the case-case study, we found significant similarity between patients with MRSA resistant or susceptible to SMX/TMP, with few relevant differentiating factors. Mortality in the cohort was associated with pulmonary (HR=2.24; 95% CI=1.40-3.57) and skin/soft tissue (HR=2.95, 95% CI=1.44-6.07) focus, Charlson comorbidity index (HR=1.15; 95% CI=1.08-1.23), lung disease (HR=1.64; 95% CI=1.08-2.52), and the presence of a central venous catheter (HR=2.08; 95% CI=1.23-3.51). On the other hand, appropriate antibiotic therapy was associated with a lower and delayed progression to death (HR=0.29; 95% CI=0.18-0.48). The COVID-19 pandemic had no impact on the prognosis. Conclusion: Our studies indicate a change in the clonal distribution of MRSA in HCFMB/UNESP, but without correspondence between the increased sensitivity to SMX/TMP and the overall decrease in mortality among patients with MRSA BSIs or those with MRSA strains susceptible to SMX/TMP. Our data align with literature reports indicating a high mortality rate among patients with MRSA BSIs, suggesting the need for improvements in the care of such patients through the optimization of preventive (MRSA spread control), diagnostic (increased presumption), and, primarily, prompt institution of appropriate antimicrobial therapy (anti-MRSA).
Context: Methicillin-resistant Staphylococcus aureus (MRSA), resistant to almost all beta-lactam antimicrobials, causes great number of bloodstream infections (BSIs), with high case-fatality ratios. MRSA strains of different lineages are no longer restricted to their environments of origins, with interchange occurring between thosen of hospital, community and animal origins. In past decades, the Brazilian epidemic clone predominated as the cause of nosocomial BSI, and it carried the SCCmec type III (Staphylococcal Chromosome Cassette, type III) in its chromosome, associated with resistance to multiple drugs in addition to beta-lactam. Recent studies indicate the replacement of this clone by others carrying SCCmec II or IV. Susceptibility to antimicrobials such as sulfamethoxazole/trimethoprim (SMX/TMP), clindamycin, and ciprofloxacin has been used as an indicator of this clone replacement. Objective: To identify epidemiological, clinical, and resistance changes observed in BSIs caused by MRSA over time. Method: Our study was conducted in two stages, both through the analysis of the database of the Hospital das Clínicas of the Botucatu Medical School, belonging to the São Paulo State University. In the first, ecological stage, we used a time-series analysis strategy (Joinpoint Regression) to identify changes in the trend of resistance in MRSA BSIs to SMX/TMP, clindamycin, and ciprofloxacin, in the period from 2005 to 2019. In a second study, we used an individual-based approach to BSIs cases diagnosed between 2012 and 2021: a case-case analysis to identify differences in predictors of BSI caused by MRSA susceptible versus resistant to SMX/TMP, followed by a cohort study of factors associated with death in patients with BSIs due to MRSA. Results: In the ecological study we observed an abrupt drop in resistance to SMX/TMP from 2008 onwards, with a slight increase after 2018. This trend was not coincident with those of resistance to clindamycin and ciprofloxacin. In the case-case study, we found significant similarity between patients with MRSA resistant or susceptible to SMX/TMP, with few relevant differentiating factors. Mortality in the cohort was associated with pulmonary (HR=2.24; 95% CI=1.40-3.57) and skin/soft tissue (HR=2.95, 95% CI=1.44-6.07) focus, Charlson comorbidity index (HR=1.15; 95% CI=1.08-1.23), lung disease (HR=1.64; 95% CI=1.08-2.52), and the presence of a central venous catheter (HR=2.08; 95% CI=1.23-3.51). On the other hand, appropriate antibiotic therapy was associated with a lower and delayed progression to death (HR=0.29; 95% CI=0.18-0.48). The COVID-19 pandemic had no impact on the prognosis. Conclusion: Our studies indicate a change in the clonal distribution of MRSA in HCFMB/UNESP, but without correspondence between the increased sensitivity to SMX/TMP and the overall decrease in mortality among patients with MRSA BSIs or those with MRSA strains susceptible to SMX/TMP. Our data align with literature reports indicating a high mortality rate among patients with MRSA BSIs, suggesting the need for improvements in the care of such patients through the optimization of preventive (MRSA spread control), diagnostic (increased presumption), and, primarily, prompt institution of appropriate antimicrobial therapy (anti-MRSA).
Descrição
Palavras-chave
MRSA, Infecção da corrente sanguínea, Resistência antimicrobiana, Sulfametoxazol/Trimetoprim, Epidemiologia
Como citar
MARTINS, Maria Aparecida Vitagliano. Staphylococcus Aureus resistente à meticilina associado a serviços de saúde: patógeno persistente e ou epidemiologia em transição? Orientador(a): Carlos Magno C. B. Fortaleza. Coorientador(a): Karen Ingrid Tasca. 2024. Tese (Doenças Tropicais) - Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp), Botucatu, 2024.