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Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.

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BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.

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OBJECTIVE: To identify urinary catheter (UC)-associated urinary tract infection (CAUTI) incidence and risk factors. DESIGN: A prospective cohort study. SETTING: The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PARTICIPANTS: The study included 169,036 patients, hospitalized for 1,166,593 patient days. METHODS: Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression. RESULTS: Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower-middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001). CONCLUSIONS: CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

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PURPOSE: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. METHODS: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. RESULTS: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01-1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01-1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06-1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08-1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75-4.49; p < 0.0001. The periods 2014-2016 and 2017-2019 had significantly higher risks than the period 2020-2022. Suprapubic catheters showed similar risks as indwelling catheters. CONCLUSION: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

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OBJECTIVE: To identify central-line (CL)-associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs). DESIGN: From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms. SETTING: The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PATIENTS: In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs. METHODS: For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs). RESULTS: The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03-1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03-1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03-1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23-1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31-4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22-3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09-2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11-6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57-3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81-3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71-3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96-2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02-2.18; P = .04). CONCLUSIONS: The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

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BACKGROUND: Our objective was to identify central line (CL)-associated bloodstream infections (CLABSI) rates and risk factors in Latin-America. METHODS: From January 1, 2014 to February 10, 2022, we conducted a multinational multicenter prospective cohort study in 58 ICUs of 34 hospitals in 21 cities in 8 Latin American countries (Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama). We applied multiple-logistic regression. Outcomes are shown as adjusted-odds ratios (aOR). RESULTS: About 29,385 patients were hospitalized during 92,956 days, acquired 400 CLABSIs, and pooled CLABSI rate was 4.30 CLABSIs per 1,000 CL-days. We analyzed following 10 variables: Gender, age, length of stay (LOS) before CLABSI acquisition, CL-days before CLABSI acquisition, CL-device utilization (DU) ratio, CL-type, tracheostomy use, hospitalization type, intensive care unit (ICU) type, and facility ownership, Following variables were independently associated with CLABSI: LOS before CLABSI acquisition, rising risk 3% daily (aOR=1.03;95%CI=1.02-1.04; P < .0001); number of CL-days before CLABSI acquisition, rising risk 4% per CL-day (aOR=1.04;95%CI=1.03-1.05; P < .0001); publicly-owned facility (aOR=2.33;95%CI=1.79-3.02; P < .0001). ICU with highest risk was medical-surgical (aOR=2.61;95%CI=1.41-4.81; P < .0001). CL with the highest risk were femoral (aOR=2.71;95%CI=1.61-4.55; P < .0001), and internal-jugular (aOR=2.62;95%CI=1.82-3.79; P < .0001). PICC (aOR=1.25;95%CI=0.63-2.51; P = .52) was not associated with CLABSI risk. CONCLUSIONS: Based on these findings it is suggested to focus on reducing LOS, CL-days, using PICC instead of femoral or internal-jugular; and implementing evidence-based CLABSI prevention recommendations.

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Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21-9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34-7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17-1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15-1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22-5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78-3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79-3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51-0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

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BACKGROUND: The International Nosocomial Infection Control Consortium has found a high ICU mortality rate. Our aim was to identify all-cause mortality risk factors in ICU-patients. METHODS: Multinational, multicenter, prospective cohort study at 786 ICUs of 312 hospitals in 147 cities in 37 Latin American, Asian, African, Middle Eastern, and European countries. RESULTS: Between 07/01/1998 and 02/12/2022, 300,827 patients, followed during 2,167,397 patient-days, acquired 21,371 HAIs. Following mortality risk factors were identified in multiple logistic regression: Central line-associated bloodstream infection (aOR:1.84; P<.0001); ventilator-associated pneumonia (aOR:1.48; P<.0001); catheter-associated urinary tract infection (aOR:1.18;P<.0001); medical hospitalization (aOR:1.81; P<.0001); length of stay (LOS), risk rises 1% per day (aOR:1.01; P<.0001); female gender (aOR:1.09; P<.0001); age (aOR:1.012; P<.0001); central line-days, risk rises 2% per day (aOR:1.02; P<.0001); and mechanical ventilator (MV)-utilization ratio (aOR:10.46; P<.0001). Coronary ICU showed the lowest risk for mortality (aOR: 0.34;P<.0001). CONCLUSION: Some identified risk factors are unlikely to change, such as country income-level, facility ownership, hospitalization type, gender, and age. Some can be modified; Central line-associated bloodstream infection, ventilator-associated pneumonia, catheter-associated urinary tract infection, LOS, and MV-utilization. So, to lower the risk of death in ICUs, we recommend focusing on strategies to shorten the LOS, reduce MV-utilization, and use evidence-based recommendations to prevent HAIs.

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Environmental cleaning and disinfection are fundamental health care-associated infection prevention measures. This study aimed to evaluate the disinfection compliance of high-touch surfaces in a COVID-19-only intensive care unit, using a fluorescent marker. It was divided into 3 phases, baseline assessment, educational feedback, and post feedback. Disinfection compliance improved significantly from the first to the third phase, 14.3% to 51.4% (P < .001), respectively.

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Resumo: Introdução: A Política Nacional de Saúde Integral de Lésbicas, Gays, Bissexuais, Travestis e Transexuais (PNSILGBT) é formada por um agrupamento de diretrizes e planos, sendo um eixo importante para formação dos profissionais de saúde, por meio de ações e estratégias específicas, para minimizar os efeitos da discriminação de gênero e sexualidade de uma população historicamente marginalizada. Na literatura, encontram-se estudos que evidenciam a falta de carga horária específica para gênero e sexualidade, a falta de transversalidade da temática LGBTI+ ou ainda a ausência da abordagem de aspectos socioeconômicos, políticos e raciais da saúde LGBTI+ dentro dos currículos de Medicina no Brasil e no mundo. Objetivo: Este estudo teve como objetivo comparar a percepção entre discentes assumidamente LGBTI+ e discentes heterossexuais no que concerne à formação dos médicos sobre a saúde de minorias sexuais e de gênero. Método: Trata-se de um estudo qualitativo, em profundidade, com análise de discurso de grupos focais, um com alunos LGBTI+ e outro com alunos não LGBTI+, em que se aplicou um questionário semiestruturado com base na análise de práticas discursivas de Spink. Resultado: A análise dos grupos identificou como questões mais pertinentes: pouca carga horária programática; falta de transversalidade; abordagem do tema com olhar pejorativo e preconceituoso; associação da população LGBTI+ com doenças infectocontagiosas ou psiquiátricas; ausência de abordagem dos aspectos socioeconômicos, culturais e raciais da temática; e atenção primária à saúde como espaço de maior abertura para discussões sobre gênero e sexualidade; Conclusão: Há uma percepção, em ambos os grupos, de que o ensino de saúde LGBTI+ é insuficiente e há um despreparo dos alunos para a abordagem da temática de gênero e sexualidade, o que gera impacto direto na assistência em saúde dessa população. Além disso, são necessários mais estudos sobre educação médica em saúde LGBTI+.

Abstract: Introduction: Brazil national public policy for the comprehensive healthcare of the LGBTi+ population consists of several guidelines and plans that include the training of health professionals. Through actions and strategies, it aims to minimize the effects of gender and sexuality discrimination on this historically marginalized population. Studies were found that show a lack of specific hours for gender and sexuality, a lack of transversality of the LGBTI+ topic and a lack of addressing the socioeconomic, political and racial aspects of LGBTI+ health in the curricula of Faculties of Medicine in Brazil and in the world. Objective: To compare the perception between admittedly LGBTI+ students and heterosexual students regarding the training of medical students on the health of sexual and gender minorities. Methodology: An in-depth qualitative study was carried out through two focus groups: one with LGBTI+ students and the other with non-LGBTI+ students. In addition, a semi-structured questionnaire was also applied. The analysis was made through the analysis of Spink's Discursive Practices. Result: Current problems were identified: low number of programmatic hours on the topic; lack of transversality; addressing the topic through a pejorative and prejudiced look; association of LGBTI+ people with infectious or psychiatric diseases; lack of addressing socioeconomic, cultural and racial aspects; Primary Care as a space of greater openness to fight against the cisheteronormative hegemony; Conclusion: LGBTI+ health education is still insufficient, as students feel unprepared to address the issue of gender and sexuality, which directly impacts the healthcare of this population. Additionally, further studies on medical education in LGBTI+ health are needed.

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BACKGROUND: The International Nosocomial Infection Control Consortium (INICC) has found a high ICU mortality rate in Latin America. METHODS: A prospective cohort study in 198 ICUs of 96 hospitals in 46 cities in 12 Latin American countries to identify mortality risk factors (RF), and data were analyzed using multiple logistic regression. RESULTS: Between 07/01/1998 and 02/12/2022, 71,685 patients, followed during 652,167 patient-days, acquired 4700 HAIs, and 10,890 died. We prospectively collected data of 16 variables. Following 11 independent mortality RFs were identified in multiple logistic regression: ventilator-associated pneumonia (VAP) acquisition (adjusted odds ratio [aOR] = 1.17; 95% CI: 1.06-1.30; p < 0.0001); catheter-associated urinary tract infection (CAUTI) acquisition (aOR = 1.34; 95% CI: 1.15-1.56; p < 0.0001); older age, rising risk 2% yearly (aOR = 1.02; 95% CI: 1.01-1.02; p < 0.0001); longer indwelling central line(CL)-days, rising risk 3% daily (aOR = 1.03; 95% CI: 1.02-1.03; p < 0.0001); longer indwelling urinary catheter(UC)-days, rising risk 1% daily (aOR = 1.01; 95% CI: 1.01-1.26; p < 0.0001); higher mechanical ventilation (MV) (aOR = 6.47; 95% CI: 5.96-7.03; p < 0.0001) and urinary catheter-utilization ratio (aOR = 1.19; 95% CI: 1.11-1.27; p < 0.0001); lower-middle level income country (aOR = 2.94; 95% CI: 2.10-4.12; p < 0.0001); private (aOR = 1.50; 95% CI: 1.27-1.77; p < 0.0001) or public hospital (aOR = 1.47; 95% CI: 1.24-1.74; p < 0.0001) compared with university hospitals; medical hospitalization instead of surgical (aOR = 1.67; 95% CI: 1.59-1.75; p < 0.0001); neurologic ICU (aOR = 4.48; 95% CI: 2.68-7.50; p < 0.0001); adult oncology ICU (aOR = 3.48; 95% CI: 2.14-5.65; p < 0.0001); and others. CONCLUSION: Some of the identified mortality RFs are unlikely to change, such as the income level of the country, facility ownership, hospitalization type, ICU type, and age. But some of the mortality RFs we found can be changed, and efforts should be made to reduce CL-days, UC-days, MV-utilization ratio, UC-utilization ratio, and lower VAPs and CAUTI rates.

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With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

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Bacteriophages (phages) are viruses considered to be natural bacterial predators and widely detected in aquatic environments. Sewage samples are an important source of phage isolation since high density and diversity of bacterial cells are present, due to human, animal and household fluids. This study aims to investigate and characterise phages against an extremely drug-resistant (XDR) lineage, Klebsiella pneumoniae ST16, using sewage samples from different parts of the World. Sewage samples from Brazil, Bangladesh, Saudi Arabia, Thailand and the United Kingdom were collected and used to investigate phages against ten K. pneumoniae ST16 (hosts) recovered from infection sites. The phages were microbiological and genetically characterised by double-agar overlay (DLA), transmission electron microscopy and Illumina WGS. The host range against K. pneumoniae belonging to different sequence types was evaluated at different temperatures by spot test. Further phage characterisation, such as efficiency of plating, optimal phage temperature, and pH/temperature susceptibility, were conducted. Fourteen lytic phages were isolated, belonging to Autographiviridae, Ackermannviridae, Demerecviridae, Drexlerviridae, and Myoviridae families, from Brazil, Bangladesh, Saudi Arabia and Thailand and demonstrated a great genetic diversity. The viruses had good activity against our collection of clinical K. pneumoniae ST16 at room temperature and 37 °C, but also against other important Klebsiella clones such as ST11, ST15, and ST258. Temperature assays showed lytic activity in different temperatures, except for PWKp18 which only had activity at room temperature. Phages were stable between pH 5 and 10 with minor changes in phage activity, and 70 °C was the temperature able to kill all phages in this study. Using sewage from different parts of the World allowed us to have a set of highly efficient phages against an K. pneumoniae ST16 that can be used in the future to develop new tools to combat infections in humans or animals caused by this pathogen.

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Bacteriophages are the most abundant organisms on Earth. As there are few effective treatment options against some pathogens, the interest in the bacteriophage control of multi-drug-resistant bacterial pathogens is escalating, especially for Klebsiella pneumoniae. This study aimed to develop a phage-based solution to the rising incidence of extensively drug-resistant clinical Klebsiella pneumoniae sequence type (ST16) infections starting from a set of phages recently characterized against this lineage. A phage-cocktail (Katrice-16) composed of eight lytic phages was characterized for potential use in humans. In vitro and in vivo broth inhibition and Galleria mellonella rescue assays were used to demonstrate the efficacy of this approach using a collection of 56 strains of K. pneumoniae ST16, with distinct genetic backgrounds that were collected from clinical infections from four disparate nations. Additionally, Katrice-16 anti-biofilm activity, synergism with meropenem, and activity in human body fluids were also assessed. Katrice-16 was highly active in vitro against our K. pneumoniae ST16 collection (AUC% median = 86.48%; Q1 = 83.8%; Q2 = 96.85%; Q3 = 98.85%). It additionally demonstrated excellent in vivo activity in G. mellonella rescue assays, even with larvae infected by isolates that exhibited moderate in vitro inhibition. We measured significant anti-biofilm activity over 12 h (p = .0113) and synergic activity with meropenem. In addition, we also demonstrate that Katrice-16 maintained high activity in human body fluids. Our results indicate that our cocktail will likely be an effective solution for human infections with this increasingly prevalent and often highly resistant bacterial clone.

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OBJECTIVE: To describe the undetected circulation of an epidemic BKC-1-producing Klebsiella pneumoniae ST442 clone, occasioning the first reported outbreak of the infrequent carbapenemase BKC-1. METHODS: Six hundred and forty-seven K. pneumoniae isolates (2008-2017) with reduced susceptibility to carbapenems were screened for blaBKC-1. BKC-1-positive isolates were typed using pulsed-field gel electrophoresis and multi-locus sequence typing. Susceptibility profiles were determined by broth microdilution, and additional antimicrobial resistance genes (ARGs) were investigated by polymerase chain reaction. Some isolates were submitted to full genomic characterization by whole-genome sequencing (Illumina MiSeq and MinIon), and in-vivo virulence studies using the Galleria mellonella model. RESULTS: Sixteen (2.5%) K. pneumoniae, from 15 patients, carrying blaBKC-1 were found between 2010 and 2012. Among these patients, the all-cause mortality rate was 54.5%. A major clone - A1-ST442 (13/16) - was isolated during the study period. The BKC-1-producing isolates had a multi-drug-resistant phenotype, remaining susceptible to gentamicin (87.5%) and ceftazidime-avibactam (100%) alone. The presence of two carbapenemases - blaBKC-1 and blaKPC-2 - was detected in six isolates, increasing the ß-lactam minimum inhibitory concentration significantly. Additionally, other ARGs were identified on A1-ST442 and B1-ST11 clones. The B1-ST11 clone was more virulent than the A1-ST442 clone. CONCLUSION: An undetected outbreak caused predominantly by a BKC-1-positive A1-ST442 clone between 2010 and 2012 was identified 10 years later in a Brazilian hospital. The misidentification of BKC-1 may have worsened the spread of resistant clones; this reinforces the need for correct and rapid identification of antimicrobial resistance mechanisms in hospitals.

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BACKGROUND: There is an increasing use of daily chlorhexidine gluconate (CHG) bathing to decrease healthcare associated infections (HAI). Daily bathing of patients with CHG has been successfully used to prevent multidrug-resistant organisms (MDROs) HAI in intensive care units (ICU). METHODS: This was a 12-month, single-center, open, cluster randomized trial, conducted at four ICUs of the University Hospital of Universidade Federal de São Paulo, Unifesp, Brazil. ICUs were randomized to either perform daily bathing of the patients with pH neutral soap and water - control units, or daily bathing with 2% CHG detergent solution - intervention units. We evaluated the incidence density rate of central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), catheter associated urinary tract infection (CAUTI), Klebsiella pneumoniae carbapenemase (KPC)-producing enterobacteria HAI, and death in the intervention and control units. RESULTS: A total of 1,640 admissions of 1,487 patients occurred during the study period (41.2% control group, and 58.8% intervention group). Incidence density rates of KPC-producing enterobacteria HAI were 5.01 and 2.25 infections/1000 patient-days in the control units and in the intervention units (p = 0.013) and mortality rates were 28.7% and 18.7% in the control units and in the intervention units (p<0.001), respectively. No difference between groups was observed in CLABSI incidence (p = 0.125), VAP incidence (p = 0.247) and CAUTI incidence (p = 0.435). No serious skin reactions were noted in either study group. Daily 2% CHG detergent solution bathing is a feasible, low cost option for HAI prevention in ICU.

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Abstract With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.