Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up

OBJECTIVE To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS Blood donors from 1994 to 2012, identified with positive anti- HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15–1.71), age under or equal to 50 years (PR = 1.36; 95%CI 1.12–1.65) and non-Caucasians (PR = 1.53; 95%CI 1.27–1.84). CONCLUSIONS About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Approach to Endoscopic Procedures: A Routine Protocol from a Quaternary University Referral Center Exclusively for Coronavirus Disease 2019 Patients

OBJECTIVES: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations. METHOD: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit. RESULTS: Our institution, located in Sa˜o Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission. CONCLUSION: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times

Hepatitis G (GBV-C) influence in the prognosis of HIV- infected women

INTRODUÇÃO: O vírus da hepatite G (GBV-C) foi descoberto simultaneamente por dois grupos de pesquisa que buscavam identificar um agente causador de hepatite pós-transfusional não-A, não-B e não-C. Trata-se de um vírus linfotrópico que replica primariamente em células mononucleares do sangue periférico (PBMC), baço e medula óssea, sendo a replicação hepática menos importante. Sabe-se que, após um período de viremia assintomática, a maioria dos carreadores virais clareia o vírus ao longo do tempo havendo surgimento do anticorpo contra a glicoproteína do envelope viral, anti-E2. Uma vez que, provavelmente, não exista nenhuma associação entre o GBV-C e qualquer doença identificada até o momento, o mesmo tem sido considerado um vírus humano não patogênico. Entretanto, alguns estudos demonstraram haver uma interação benéfica entre o GBV-C e HIV a ponto de retardar a progressão da infecção pelo HIV para aids. OBJETIVOS: Avaliar a prevalência da viremia e de anticorpos contra a glicoproteína anti-E2 e estudar o efeito da interação GBV-C e HIV ao longo do acompanhamento de pacientes femininas baseado em valores da média e mediana de linfócitos T CD4+ , da carga viral do HIV e da carga viral quantitativa do GBV-C RNA. MÉTODOS: Foram estudas 248 pacientes femininas portadoras da infecção pelo HIV acompanhadas por um período de cerca de 10 anos, tendo como término de estudo a data limite de 01/01/2008, ou a data da última consulta no ambulatório ou a data do óbito. RESULTADOS: Das 115 pacientes expostas, 57 eram GBV-C RNA positivas (23%) e 58 eram anti-E2 positivas (23%). Não houve achado da presença concomitante do GBV-C RNA e do anticorpo anti-E2 nas pacientes estudas. Com relação à contagem de linfócitos T CD4+ e de carga viral basal do HIV no início do estudo, não observamos diferença estatística entre os valores em relação aos grupos (GBV-C RNA-/anti-E2- , GBV-C RNA+/anti-E2 - e GBV-C RNA -/anti-E2+), sendo o p=0,36 e 0,713, respectivamente. O risco relativo de óbito para o grupo GBV-C+/anti-E2- foi 63% menor do que para o grupo GBV-C-/anti-E2-. CONCLUSÃO: A prevalência da viremia por GBV-C RNA e a do anticorpo anti-E2 foi de 23%, perfazendo uma frequência de exposição ao GBV-C de 46%. Em análise multivariada, apenas a carga viral do HIV, maior que 100.000 cópias/mL, e manifestação de doença oportunística ao longo do acompanhamento das pacientes estiveram associadas à melhora da sobrevida. Provavelmente, o uso da terapia antirretroviral para o HIV foi fator limitante na análise de efeito protetor do GBV-C RNA em nossa casuísticaINTRODUCTION: GB virus C (GBV-C) was discovered by two research groups that aimed to identify a possible agent responsible for a non-A, non-B and non-C pos-transfusion hepatitis. There is remarkable evidence that GBV-C is a lymphotropic virus that primarily replicates in PBMCs, spleen and bone marrow. This virus does not appear to be hepatotropic and does not replicate effectively in hepatocytes. After an asymptomatic viremia period, most subjetcs clear the virus over time with the development of antibody against a viral envelope glycoptrotein (anti-E2). Since there is probably no association between GBV-C and any identify disease, this virus has been considered not pathogenic. However, according to some studies, GBV-C co-infection in HIV seropositive patients is associated with a slower disease progression and longer survival after AIDS development in HIV infected patients. Objective: To evaluate the prevalence of GBV-C viremia, anti- E2 antibody and assess the effect of the interaction of GBV-C and HIV in an exclusive female cohort, in a follow up period of up to 10 years. Methodos: Two hundred forty-eight HIV infected women were enrolled in the study. Follow-up sample was obtained from 248 patients. Laboratorial variables as mean and median of values of CD4, HIV and GBV-C quantitative viral load, and clinical parameters as HAART use, OIs influence on survival were investigated. Results: One hundred and fifteen subjects were exposed to GBV-C: 57 were GBV-C RNA positive (23%) and 58 were anti-E2 antibody positive (23%). Viral RNA with concomitant anti-E2 antibodies was not found in any patient. There was no statistical difference among three studied groups (GBV-C RNA-/anti-E2 - , GBV-C RNA+/anti-E2- and GBV-C RNA -/anti-E2+), regarding CD4+ and viral load baselines (p=0,360 and 0,713, respectively). Relative risk of death for GBV-C RNA+/anti-E2- group was 63% lower than the GBV-C-/anti-E2 group. Conclusion: Forty-six percent of the enrolled individuals were exposed to GBV-C virus. Multivariate analysis demonstrated that only HIV load higher than 100.000 copies/mL and opportunistic disease during the follow-up period were associated to longer survival after AIDS development. Probably, antiretroviral therapy for HIV in our study blurred the observation of a putative protective effect related to GBVC RN

Impact of an antimicrobial stewardship program intervention associated with the rapid identification of microorganisms in patients with gram-negative bacteremia

Resumo. A combinação de estratégias para testes de diagnóstico rápido (TDR) com intervenção em tempo real para uso racional de antimicrobianos (ATM) pode melhorar os desfechos em pacientes com infecções de corrente sanguínea (ICS) por bacilos gram-negativos (BGN) em unidades de terapia intensiva (UTIs). O objetivo do estudo foi avaliar o impacto da intervenção de TDR e comunicação rápida em desfechos clínicos e de consumo e custos de antimicrobianos em pacientes com ICS por BGN internados em UTIs. Trata-se de um estudo quase experimental do tipo pré e pós-intervenção realizado nas UTIs do Instituto Central do Hospital das Clínicas (ICHC) durante o período de Março de 2018 a Maio de 2019, período pré intervenção, e de Setembro 2020 a Outubro 2021, período intervenção, sendo incluídos pacientes com ICS por BGN em UTIs. No período pré intervenção foram coletados dados de resultados de testes microbiológicos laboratoriais realizados por metodologia convencional e prescrição do antimicrobiano de forma passiva em prontuário médico eletrônico, sem nenhuma intervenção. No período de intervenção a técnica de Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) utilizada para identificação das bactérias passou a ser feita diretamente do frasco da hemocultura positiva, houve comunicação direta do pesquisador com os médicos prescritores para avisar dos resultados microbiológicos (Gram, identificação da espécie e teste de sensibilidade aos antimicrobianos) em tempo real e houve também pesquisa de genes de resistência. A detecção dos genes de resistência foi realizada pela técnica de PCR multiplex através do XGEN MULTI SEPSE FLOW CHIP (Mobius) utilizando o kit para bactérias gram-negativas em associação ao equipamento HybriSpot (HS12 AUTO) diretamente do frasco de hemocultura positivada. Os períodos foram comparados com relação aos desfechos clínicos de mortalidade em 30 dias, tempo de internação hospitalar e na UTI e com relação ao consumo de ATM utilizando-se dias de terapia (DOT) e custos em reais por análise uni e multivariada. Foram incluídos 216 episódios de bacteremia por BGN, sendo 114 no período pré intervenção e 102 no período intervenção. A mediana de idade dos pacientes nos períodos pré intervenção e intervenção foi de 56 anos (41-62) e 59 anos (47-69), p=0,057, respectivamente sendo o sexo masculino mais prevalente em ambos os períodos. No período intervenção, os pacientes eram mais graves (SAPS3= 64, IIQ 50-76) e tivemos a prevalência de pacientes infectados pelo SARS-CoV-2 (44%). A origem da maioria dos isolados no período pré intervenção foram provenientes de ICS primárias (50,8%), seguidas de abdominal (14,9%) e do trato respiratório (11,4%). No período de intervenção a origem das ICS foi primária (47,1%), seguida de infecções do trato respiratório (27,5%) e urinárias (8,8%). A Klebsiella pneumoniae foi a bactéria mais prevalente para ambos os períodos (43% vs. 32,4%, p=0,043) e a distribuição dos patógenos foi semelhante nos dois períodos, exceto pela prevalência significativa maior de Pseudomonas aeruginosa no período intervenção (6,1% vs. 21,6%; p=0,002). A taxa de Enterobactérias resistentes aos carbapenêmicos em ambos os períodos foi semelhante, 24,6% vs. 15,7%, p=0,14, respectivamente. No período intervenção, blaCTX-M foi o gene de resistência mais comumente detectado (68,6%), seguido por blaOXA (41,2%) e blaKPC (27,4%). O estudo não demonstrou impacto na mortalidade em 30 dias entre o período pré intervenção e intervenção, (25% vs 35%; p=0,115), respectivamente. O tempo de permanência no hospital e tempo de permanência na UTI foi significativamente menor no período de intervenção [(44 dias vs. 39 dias; p= 0,005) e (17 dias vs. 13 dias; p= 0,033)], respectivamente. Na análise multivariada para fatores de risco relacionados a mortalidade em 30 dias, somente a infecção pelo SARS Cov-2 demonstrou ser variável independente para esse risco (OR= 1,54, IC95% 1,02-2,29; p=0,036). O tempo médio de duração da terapia antimicrobiana foi significativamente diferente no período pré e intervenção (9,13 vs. 7,8 dias; p=0,013), respectivamente. O tempo para os resultados dos testes microbiológicos (TAT) diretamente do frasco de hemocultura, Gram, MALDI-TOF e teste de sensibilidade, tiveram redução significativa entre os períodos pré e intervenção [(2h43min vs. 1h32min; p< 0,001), (26h31min vs. 9h31min; p<0,001) e 54h14min vs. 48h28min, p=0,005), respectivamente]. O consumo geral de antimicrobianos foi de 1.381 DOT/1.000 dias-presentes no período pré intervenção comparado a 1.262 DOT/1.000 dias-presentes no período de intervenção (p=0,032). Essa redução do consumo geral foi atribuída ao menor uso de antimicrobianos no tratamento de bactérias gram-positivas e ao menor uso da antimicrobianos da classe dos carbapenêmicos [(475 DOT/1.000 dias-presente vs. 270 DOT/1.000 dias-presente; p=0,004) e (836 DOT/1.000 dias-presente vs. 543 DOT/1.000 dias-presente); p=0,04)], respectivamente. Conclui-se que a intervenção do estudo não demostrou impacto na mortalidade em 30 dias, muito provavelmente pela presença da infecção pelo SARS CoV-2 no período intervenção e consequentemente, maior gravidade dos pacientes, o que pode ter contribuído para não redução da mortalidade. Contudo, houve impacto no tempo de internação hospitalar e na UTI, bem como no consumo e custos de antimicrobianos. Houve também diferenças no TAT com a incorporação do MALDI-TOF realizado diretamente do frasco da hemocultura positiva que deve ser incorporado de maneira rotineira pelos laboratórios que utilizam esta técnica. Todas as ferramentas de uso racional de antimicrobiano baseadas em testes de diagnóstico microbiológico rápido e sua comunicação em tempo real aos médicos prescritores, por agregar valor e informações para uma tomada de decisão segura, são estratégias que resultam em benefícios diretos e indiretos relacionados tanto ao uso racional de antimicrobianos e potencial de menor indução de resistência bacteriana como também ao ônus econômico desta classe de medicamentosThe combination of rapid diagnostic testing (RDT) strategies with real-time intervention for rational use of antimicrobials (ATM) can improve outcomes in patients with bloodstream infections (BSIs) caused by gram-negative bacteria (GNB) in intensive care units (ICUs). The aim of the study was to assess the impact of RDT intervention and rapid communication on clinical and antimicrobial consumption and cost outcomes in patients with BSIs from GNB admitted to ICUs. This is a quasi-experimental study of the pre- and post-intervention type carried out in the ICUs of the Instituto Central do Hospital das Clínicas (ICHC) during the period from March 2018 to May 2019, pre-intervention period, and from September 2020 to October 2021, intervention period, including patients with ICS due to BGN in ICUs. In the pre-intervention period, data were collected from the results of laboratory microbiological tests performed by conventional methodology and passively prescribed antimicrobials in electronic medical records, without any intervention. During the intervention period, the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) was performed directly from the positive blood culture bottle with direct and real time communication between the researcher and the prescribing physicians to notify the microbiological results (Gram, species identification and antimicrobial sensitivity test). The detection of resistance genes was performed by the multiplex PCR technique through the XGEN MULTI SEPSE FLOW CHIP (Mobius) using the kit for GNB in association with the HybriSpot equipment (HS12 AUTO) directly from the positive blood culture bottle. The periods were compared with respect to clinical outcomes of 30-day mortality, length of hospital and ICU stay and with respect to ATM consumption using days of therapy (DOT) and costs in reais by univariate and multivariate analysis. A total of 216 episodes of BGN bacteremia were included, 114 in the pre-intervention period and 102 in the intervention period. The median age of patients in the pre-intervention and intervention periods was 56 years (41-62) and 59 years (47-69), p=0.057, respectively, with males being more prevalent in both periods. In the intervention period, patients were more severe (SAPS3= 64, IQR 50-76) and we had a prevalence of patients infected with SARS-CoV-2 (44%). The source of most isolates in the pre-intervention period came from primary BSI (50.8%), followed by abdominal (14.9%) and respiratory tract (11.4%). During the intervention period, it was from primary (47.1%), followed by respiratory (27.5%) and urinary tract (8.8%) infections. Klebsiella pneumoniae was the most prevalent bacteria for both periods (43% vs. 32.4%, p=0.043) and the distribution of pathogens was similar in both periods, except for the significantly higher prevalence of Pseudomonas aeruginosa in the intervention period (6.1% vs. 21.6%; p=0.002). The rate of carbapenem-resistant Enterobacteriaceae in both periods was similar, 24.6% vs. 15.7%, p=0.14, respectively. In the intervention period, blaCTX-M was the most detected resistance gene (68.6%), followed by blaOXA (41.2%) and blaKPC (27.4%). The study showed no impact on 30-day mortality between the pre-intervention and intervention periods (25% vs. 35%; p=0.115), respectively. Length of hospital stay, and length of ICU stay were significantly shorter in the intervention period [(44 days vs. 39 days; p=0.005) and (17 days vs. 13 days; p=0.033)], respectively. In the multivariate analysis for risk factors related to 30-day mortality, only SARS Cov-2 infection proved to be an independent variable for this risk (OR= 1.54, 95%CI 1.02-2.29; p=0.036). The mean duration of antimicrobial therapy was significantly different in the pre- and intervention period (9.13 vs. 7.8 days; p=0.013), respectively. The time for the results of microbiological tests (TAT) directly from the blood culture bottle related to Gram, MALDI-TOF and antimicrobial sensitivity test, had a significant reduction between the pre and intervention periods [(2h43min vs. 1h32min; p< 0.001), (26h31min vs. 9h31min; p<0.001) and (54h14min vs. 48h28min, p=0.005), respectively]. Overall antimicrobial consumption was 1,381 DOT/1,000 present days in the pre-intervention period compared to 1,262 DOT/1,000 present days in the intervention period (p=0.032). This reduction in overall consumption was attributed to the lower use of antimicrobials in the treatment of gram-positive bacteria and the lower use of carbapenem-class antimicrobials [(475 DOT/1,000 present days vs. 270 DOT/1,000 present days; p= 0.004) and (836 DOT/1,000 present days vs. 543 DOT/1,000 present days); p=0.04)], respectively. It is concluded that the intervention proposed in this study showed no impact on 30-day mortality, most likely due to the presence of SARS CoV-2 infection in the intervention period and, consequently, greater severity of patients, which may have contributed to the non-reduction of mortality. However, there was an impact on hospital and ICU length of stay, as well as on antimicrobial consumption and costs. There were also differences in TAT with the incorporation of MALDI-TOF performed directly from the positive blood culture bottle, which must be routinely incorporated by laboratories that use this technique. All antimicrobial rational use tools based on RDTs and their communication in real time to prescribing physicians, by adding value and information for safe decision making, are strategies that result in direct and indirect benefits related to both the use rational use of antimicrobials and the potential for lower induction of bacterial resistance as well as the economic burden of this class of drug

Impact of an Antimicrobial Stewardship Program Intervention Associated with the Rapid Identification of Microorganisms by MALDI-TOF and Detection of Resistance Genes in ICU Patients with Gram-Negative Bacteremia

Combination of strategies for rapid diagnostics tests (RDT) with real-time intervention could improve patient outcomes. We aimed to assess the impact on clinical outcomes, antimicrobial consumption, and costs in patients with gram-negative bacteremia. We designed a quasi-experimental study among 216 episodes of gram-negative bacteremia using RDT (MALDI-TOF and detection of resistance genes) directly from blood culture bottles combined with real-time communication of results. Our study did not demonstrate impact on 30-day mortality (25% vs. 35%; p = 0.115). Hospital and ICU length of stay were significantly lower in the intervention period ((44 days vs. 39 days; p = 0.005) and (17 days vs. 13 days; p = 0.033)), respectively. The antimicrobial consumption was 1381 DOT/1000 days in the pre-intervention period compared to 1262 DOT/1000 days in the intervention period (p = 0.032). Antimicrobials against gram-positive and carbapenems had a significantly reduced consumption in the intervention period. Our intervention showed no impact on 30 days-mortality, but demonstrated an impact on hospital and ICU length of stay, as well as antimicrobials consumption and costs. Knowledge of resistance genes adds value and information for safe decision making that can result in direct and indirect benefits related to the economic burden of antibiotic overuse and bacterial resistance