Terapia combinada com polimixina b no tratamento de bacteremias causadas por Klebsiella pneumoniae produtoras de carbapenemase (KPC-KP) – estudo de coorte retrospectivo

Base Teórica: Bacteremias causadas por Klebsiella pneumoniae produtoras de carbapenemase são infecções ameaçadoras da vida e com elevadas taxas de mortalidade. As Enterobacteriaceae são as principais reponsáveis por bacteremias nos hospitais brasileiros. Há limitadas opções terapêuticas e o melhor tratamento para essas infecções ainda não está definido. O racional teórico para a terapia combinada nesse cenário seria o aumento da ação bactericida e a diminuição da indução de resistência. A terapia combinada com colistina parece estar relacionada com maior sobrevida. Com relação a terapia combinada com polimixina B, no entanto, as evidências são exíguas. Objetivo: Avaliar a mortalidade em 30 dias de pacientes com bacteremias por KPC-KP com enfoque na terapia combinada.Métodos: Trata-se de um estudo de coorte retrospectivo e unicêntrico que incluiu pacientes maiores de 18 anos com diagnóstico de bacteremia por KPC-KP. O desfecho primário avaliado foi mortalidade em 30 dias. Bacteremia por KPC-KP foi definida como uma ou mais hemoculturas positivas para esse microorganismo. A identificação bacteriana e os testes de susceptibilidade foram realizados utilizando o sistema automatizado Vitek 2 (bioMérieux, France). A terapia antimicrobiana foi caracterizada como empírica (iniciada nas primeiras 48 horas) e definitiva (esquemas iniciados ou mantidos após 48 horas) e avaliada da seguinte forma: nenhuma droga ativa, monoterapia (apenas um agente ativo), terapia combinada entre uma droga ativa e uma ou mais drogas inativas e terapia combinada com duas ou mais drogas ativas A análise estatística foi realizada com o software SPSS para Windows, versão 18.0. As análises de sobrevivência foram realizadas com curvas de Kaplan-Meier e as diferenças foram avaliadas utilizando o log-rank test. Todos os testes foram bicaudais considerando um nível de significância de 95%. Um modelo de regressão de Cox foi realizado para identificar fatores independentemente relacionados com a mortalidade em 30 dias. Resultados: Foram incluídas 105 bacteremias por KPC-KP. A mortalidade em 30 dias foi de 63 (60%) pacientes. O tempo médio de sobrevida foi de 24 dias (95% IQR, 17-21 dias). A taxa de mortalidade em pacientes tratados com terapia combinada foi significativamente menor (16,5/1000 pacientes-dia) comparada com os pacientes recebendo outros regimes terapêuticos (57,5/1000 pacientes-dia). Terapia combinada (Hazard Ratio [HR]; 0,32; 95% IC, 0,18-0.57; p<0,01) e bacteremia urinária (HR; 0,29; 95% IC, 0,09- 0,95; p=0,04) foram independentemente associados com a sobrevida em 30 dias. Em contrapartida, neoplasias (HR; 1,98; 95% IC, 1,18-3,32; p=0,01), admissão por patologia clínica (HR; 2,91; 95% IC, 1,56-5,42; p<0.01) e necessidade de tratamento com droga vasoativa (HR; 2,94; 95% IC, 1,59- 5,29; p<0,01) foram independentemente associados com o desfecho primário. Conclusão: O presente estudo demonstrou uma mortalidade em 30 dias de 60% nas bacteremias por KPC-KP. A terapia combinada com pelo menos dois agentes ativos in vitro foi consistentemente associada com sobrevida em 30 dias.Background: BSI for KPC-KP is a life-threatening disease and compared to other sites of infection related to higher mortality rates. Enterobacteriaceae are the leading cause of BSI in Brazilian hospitals. There are limited treatment options and the best available treatment is still unknown. Rationale for combination therapy in this setting would be increasing bactericidal action and decreasing resistance induction. Combination therapy regimens with colistin seemed to be related with higher rates of survival. Polymyxin B combinations were studied only in a few studies. Objective: In this study we aim to evaluate 30-day mortality in KPC-KP bacteremia with particular emphasis on combination therapy. Methods: This is a single center retrospective cohort study that included patients older than 18 years diagnosed with KPC-KP BSI. The primary outcome was 30-day mortality after BSI. KPC-KP BSI was defined as one or more positive blood cultures with recovery of KPC-KP. Bacterial identification and antimicrobial susceptibility tests were performed using Vitek 2 (bioMérieux, France) automatized system. Antimicrobial therapy was defined as empirical (started on first 48 hours) and definitive (schemes initiated or maintained after 48 hours) and evaluated as follows: no active agents, monotherapy (only one active agents), combination therapy between one active agent plus one or more non-active agents and combination with two or more in vitro active agents Statistical analysis was performed using SPSS for Windows, version 18.0. Kaplan-Meier survival estimates were calculated and the difference was evaluated using the log-rank test. All tests were two-tailed and a p value < 0.05 were considered statistically significant. A Cox regression model were performed to identify independent factors related to 30-day mortality. Results: A total of 105 bloodstream infections caused by KPC-KP were included. A total of 63 (60%) patients died in the first 30 days after BSI. Median time to death was 24 days (95% IQR, 17-21 days). The mortality rate in patients treated with the combination of two antibiotics with in vitro activity was significantly lower (16.5/1000 patients-day) compared with that patients receiving other regimens (57.5/1000 patients-day). Combination therapy (Hazard Ratio [HR]; 0.32; 95% CI, 0.18-0.57; p<0.01) and urinary BSI (HR; 0.29; 95% CI, 0.09- 10 0.95; p=0.04) were independently associated to 30-day survival. On the other hand, having Cancer (HR; 1.98; 95% CI, 1.18-3.32; p=0.01), non-surgical admission (HR; 2.91; 95% CI, 1.56-5.42; p<0.01) and requirement of vasoactive drugs (HR; 2.94; 95% CI, 1.59-5.29; p<0.01) were independently associated to 30-day mortality. Conclusion: This study showed a 60% 30-day mortality in KPC-KP BSI. Combination therapy with two in vitro active agents was independently associated with 30-day survival

Terapia combinada com polimixina b no tratamento de bacteremias causadas por Klebsiella pneumoniae produtoras de carbapenemase (KPC-KP) – estudo de coorte retrospectivo

Base Teórica: Bacteremias causadas por Klebsiella pneumoniae produtoras de carbapenemase são infecções ameaçadoras da vida e com elevadas taxas de mortalidade. As Enterobacteriaceae são as principais reponsáveis por bacteremias nos hospitais brasileiros. Há limitadas opções terapêuticas e o melhor tratamento para essas infecções ainda não está definido. O racional teórico para a terapia combinada nesse cenário seria o aumento da ação bactericida e a diminuição da indução de resistência. A terapia combinada com colistina parece estar relacionada com maior sobrevida. Com relação a terapia combinada com polimixina B, no entanto, as evidências são exíguas. Objetivo: Avaliar a mortalidade em 30 dias de pacientes com bacteremias por KPC-KP com enfoque na terapia combinada.Métodos: Trata-se de um estudo de coorte retrospectivo e unicêntrico que incluiu pacientes maiores de 18 anos com diagnóstico de bacteremia por KPC-KP. O desfecho primário avaliado foi mortalidade em 30 dias. Bacteremia por KPC-KP foi definida como uma ou mais hemoculturas positivas para esse microorganismo. A identificação bacteriana e os testes de susceptibilidade foram realizados utilizando o sistema automatizado Vitek 2 (bioMérieux, France). A terapia antimicrobiana foi caracterizada como empírica (iniciada nas primeiras 48 horas) e definitiva (esquemas iniciados ou mantidos após 48 horas) e avaliada da seguinte forma: nenhuma droga ativa, monoterapia (apenas um agente ativo), terapia combinada entre uma droga ativa e uma ou mais drogas inativas e terapia combinada com duas ou mais drogas ativas A análise estatística foi realizada com o software SPSS para Windows, versão 18.0. As análises de sobrevivência foram realizadas com curvas de Kaplan-Meier e as diferenças foram avaliadas utilizando o log-rank test. Todos os testes foram bicaudais considerando um nível de significância de 95%. Um modelo de regressão de Cox foi realizado para identificar fatores independentemente relacionados com a mortalidade em 30 dias. Resultados: Foram incluídas 105 bacteremias por KPC-KP. A mortalidade em 30 dias foi de 63 (60%) pacientes. O tempo médio de sobrevida foi de 24 dias (95% IQR, 17-21 dias). A taxa de mortalidade em pacientes tratados com terapia combinada foi significativamente menor (16,5/1000 pacientes-dia) comparada com os pacientes recebendo outros regimes terapêuticos (57,5/1000 pacientes-dia). Terapia combinada (Hazard Ratio [HR]; 0,32; 95% IC, 0,18-0.57; p<0,01) e bacteremia urinária (HR; 0,29; 95% IC, 0,09- 0,95; p=0,04) foram independentemente associados com a sobrevida em 30 dias. Em contrapartida, neoplasias (HR; 1,98; 95% IC, 1,18-3,32; p=0,01), admissão por patologia clínica (HR; 2,91; 95% IC, 1,56-5,42; p<0.01) e necessidade de tratamento com droga vasoativa (HR; 2,94; 95% IC, 1,59- 5,29; p<0,01) foram independentemente associados com o desfecho primário. Conclusão: O presente estudo demonstrou uma mortalidade em 30 dias de 60% nas bacteremias por KPC-KP. A terapia combinada com pelo menos dois agentes ativos in vitro foi consistentemente associada com sobrevida em 30 dias.Background: BSI for KPC-KP is a life-threatening disease and compared to other sites of infection related to higher mortality rates. Enterobacteriaceae are the leading cause of BSI in Brazilian hospitals. There are limited treatment options and the best available treatment is still unknown. Rationale for combination therapy in this setting would be increasing bactericidal action and decreasing resistance induction. Combination therapy regimens with colistin seemed to be related with higher rates of survival. Polymyxin B combinations were studied only in a few studies. Objective: In this study we aim to evaluate 30-day mortality in KPC-KP bacteremia with particular emphasis on combination therapy. Methods: This is a single center retrospective cohort study that included patients older than 18 years diagnosed with KPC-KP BSI. The primary outcome was 30-day mortality after BSI. KPC-KP BSI was defined as one or more positive blood cultures with recovery of KPC-KP. Bacterial identification and antimicrobial susceptibility tests were performed using Vitek 2 (bioMérieux, France) automatized system. Antimicrobial therapy was defined as empirical (started on first 48 hours) and definitive (schemes initiated or maintained after 48 hours) and evaluated as follows: no active agents, monotherapy (only one active agents), combination therapy between one active agent plus one or more non-active agents and combination with two or more in vitro active agents Statistical analysis was performed using SPSS for Windows, version 18.0. Kaplan-Meier survival estimates were calculated and the difference was evaluated using the log-rank test. All tests were two-tailed and a p value < 0.05 were considered statistically significant. A Cox regression model were performed to identify independent factors related to 30-day mortality. Results: A total of 105 bloodstream infections caused by KPC-KP were included. A total of 63 (60%) patients died in the first 30 days after BSI. Median time to death was 24 days (95% IQR, 17-21 days). The mortality rate in patients treated with the combination of two antibiotics with in vitro activity was significantly lower (16.5/1000 patients-day) compared with that patients receiving other regimens (57.5/1000 patients-day). Combination therapy (Hazard Ratio [HR]; 0.32; 95% CI, 0.18-0.57; p<0.01) and urinary BSI (HR; 0.29; 95% CI, 0.09- 10 0.95; p=0.04) were independently associated to 30-day survival. On the other hand, having Cancer (HR; 1.98; 95% CI, 1.18-3.32; p=0.01), non-surgical admission (HR; 2.91; 95% CI, 1.56-5.42; p<0.01) and requirement of vasoactive drugs (HR; 2.94; 95% CI, 1.59-5.29; p<0.01) were independently associated to 30-day mortality. Conclusion: This study showed a 60% 30-day mortality in KPC-KP BSI. Combination therapy with two in vitro active agents was independently associated with 30-day survival

Effect of flexible family visitation on delirium among patients in the Intensive Care Unit: the ICU visits randomized clinical trial

Fernando Augusto Bozza. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento.Intensive Care Unit, Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil (Rosa, D. B. da Silva, Eugênio, Haack, Medeiros, Tonietto, Teixeira); Research Projects Office, HMV, Porto Alegre, Rio Grande do Sul, Brazil (Rosa, Falavigna, D. B. da Silva, Sganzerla, Santos, Kochhann, de Moura, Eugênio, Haack, Barbosa, Robinson, Schneider, de Oliveira, Jeffman, Medeiros, Hammes); Brazilian Research in Intensive Care Network (BRICNet), São Paulo, São Paulo (Rosa, Cavalcanti, Machado, Azevedo, Salluh, Nobre, Bozza, Teixeira); HCor Research Institute, São Paulo, São Paulo, Brazil (Cavalcanti); Department of Anesthesiology, Pain and Intensive Care, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil (Machado); Intensive Care Unit, Hospital Sírio-Libanês, São Paulo, São Paulo, Brazil (Azevedo); Department of Critical Care, Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, Rio de Janeiro, Brazil (Salluh, Mesquita, Bozza); Intensive Care Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil (Pellegrini, Moraes); Intensive Care Unit, Hospital Santa Cruz, Santa Cruz do Sul, Rio Grande do Sul, Brazil (Foernges); Intensive Care Unit, Hospital Santa Rita, Porto Alegre, Rio Grande do Sul, Brazil (Torelly); Intensive Care Unit, Hospital Universitário do Oeste do Paraná, Cascavel, Paraná, Brazil (Ayres, Duarte); Intensive Care Unit, Hospital do Câncer de Cascavel, Cascavel, Paraná, Brazil (Duarte); Intensive Care Unit, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil (Lovato); Intensive Care Unit, Santa Casa de Misericórdia de Feira de Santana, Feira de Santana, Bahia, Brazil (Sampaio); Intensive Care Unit, Hospital Geral Clériston Andrade, Feira de Santana, Bahia, Brazil (de Oliveira Júnior); Intensive Care Unit, Santa Casa de Misericórdia de São João Del Rei, São João Del Rei, Minas Gerais, Brazil (Paranhos); Intensive Care Unit, Hospital Regional Doutor Deoclécio Marques de Lucena, Parnamirim, Rio Grande do Norte, Brazil (Dantas, de Brito); Intensive Care Unit, Fundação Hospital Adriano Jorge, Manaus, Amazonas, Brazil (Paulo); Intensive Care Unit, Hospital Agamenon Magalhães, Recife, Pernambuco, Brazil (Gallindo); Intensive Care Unit, Hospital da Cidade, Passo Fundo, Rio Grande do Sul, Brazil (Pilau); Intensive Care Unit, Hospital Mãe de Deus, Porto Alegre, Rio Grande do Sul, Brazil (Valentim); Intensive Care Unit, Hospital de Urgências de Goiânia, Goiânia, Goiânia, Brazil (Meira Teles); Intensive Care Unit, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil (Nobre); Intensive Care Unit, Pavilhão Pereira Filho, Porto Alegre, Rio Grande do Sul, Brazil (Birriel); Intensive Care Unit, Hospital Regional do Baixo Amazonas, Santarém, Pará, Brazil (Corrêa e Castro); Intensive Care Unit, Hospital Nossa Senhora da Conceição, Porto Alegre, Rio Grande do Sul, Brazil (Specht); School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil (N. B. da Silva); Department of Public Health Sciences, Medical University of South Carolina, Charleston (Korte); Unit of Pediatric Anesthesia and Intensive Care, Ospedale dei Bambini—ASST Spedali Civili, Brescia, Italy (Giannini); Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil (Bozza).Submitted by Janaína Nascimento ([email protected]) on 2019-09-11T14:37:38Z No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-09-11T14:52:11Z (GMT) No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5)Made available in DSpace on 2019-09-11T14:52:11Z (GMT). No. of bitstreams: 1 ve_Rosa_Regis_etal_INI_2019.pdf: 616825 bytes, checksum: 2aae5be305137324e272a08cc32e9270 (MD5) Previous issue date: 2019Múltipla - Ver em Notas.IMPORTANCE: The effects of intensive care unit (ICU) visiting hours remain uncertain. OBJECTIVE: To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium. DESIGN, SETTING AND PARTICIPANTS: Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018. INTERVENTIONS: Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation. MAIN OUTCOMES AND MEASURES: Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory). RESULTS: Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, −1.7% [95% CI, −6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, −0.8% [95% CI, −2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, −3.8% [95% CI, −4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, −1.6 [95% CI, −2.3 to −0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, −1.2 [95% CI, −2.0 to −0.4]; P = .003) were significantly better with flexible visitation. CONCLUSIONS AND RELEVANCE: Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium