Browsing by Author "Araos, Rafael"
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Item Acquisition of Multidrug-resistant Organisms in the Absence of Antimicrobials(2018) D’Agata, Erika M. C.; Varu, Aby; Geffert, Sara F.; Araos, Rafael; Mitchell, Susan; Situ, Aaron; Cameron, ChrisA nested case-control study among 137 nursing home residents who did not receive antimicrobials, of whom 44 acquired a multidrug-resistant organism, was performed. Risk factors for acquisition included gastrointestinal medications that affect the gut microbiome, number of visits from healthcare workers, pressure ulcers, and not residing in a dementia unit.Item Antimicrobial Resistance Gene Prevalence in a Population of Patients with Advanced Dementia Is Related to Specific Pathobionts(2020-03) Rowan-Nash, Aislinn D.; Araos, Rafael; D'Agata, Erika M.C.; Belenky, PeterLong-term care facilities are significant reservoirs of antimicrobial-resistant organisms, and patients with advanced dementia are particularly vulnerable to multidrug-resistant organism (MDRO) acquisition and antimicrobial overuse. In this study, we longitudinally examined a group of patients with advanced dementia using metagenomic sequencing. We found significant inter- and intra-subject heterogeneity in microbiota composition, suggesting temporal instability. We also observed a link between the antimicrobial resistance gene density in a sample and the relative abundances of several pathobionts, particularly Escherichia coli, Proteus mirabilis, and Enterococcus faecalis, and used this relationship to predict resistance gene density in samples from additional subjects. Furthermore, we used metagenomic assembly to demonstrate that these pathobionts had higher resistance gene content than many gut commensals. Given the frequency and abundances at which these pathobionts were found in this population and the underlying vulnerability to MDRO of patients with advanced dementia, attention to microbial blooms of these species may be warranted.Item Bacteriemia en daño hepático crónico(2011) Munita, José; Araos, Rafael; Pérez, Jorge; Alvarez, Alejandra; Canals, Magdalena; Contreras, Jorge; Marcotti, Alejandra; Thompson, Luis; Noriega, LuisBacteremic infections are more frequent in patients with cirrhosis, as their immune system is compromised. Series of cirrhotic patients with bacteremia has seldom been reported in Chile. We retrospectively collected, from 2005 to 2008, 59 episodes of bacteremia in cirrhotics representing 9% of the overall number of bacteremic episodes seen in our center in the period. Spontaneous bacteremia accounted for 29% followed by those of pulmonary origin (22%). Grampositive cocci and gramnegative bacilli were responsible in 52% and 48% respectively, however gramnegative rods predominated in nosocomial bacteremias. Overall, the most frequent organisms were Staphylococcus aureus (24%) and Escherichia coli (22%). Mortality in bacteremic patients was significantly higher compared with all cirrhotic patients hospitalized in the period (37.0 vs 9.4%; p < 0.001) and MELD score was significantly correlated with mortality. Conclusion: bacteremia is a severe complication of cirrhosis and MELD score could be a useful tool to stratify risk in these patients.Item Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa(2020) Gudiol, C.; Albasanz-Puig, A.; Laporte-Amargós, J.; Pallarès, N.; Mussetti, A.; Ruiz-Camps, I.; Puerta-Alcalde, P.; Abdala, E.; Oltolini, C.; Akova, M.; Montejo, M.; Mikulska, M.; Martín-Dávila, P.; Herrera, F.; Gasch, O.; Drgona, L.; Paz Morales, H.; Brunel, A-S; García, E.; Isler, B.; Kern, W.V.; Morales, I.; Maestro-de la Calle, G.; Montero, M.; Kanj, S.S.; Sipahi, O.R.; Calik, S.; Márquez-Gómez, I.; Marin, J.I.; Gomes, M. Z. R.; Hemmatti, P.; Araos, Rafael; Peghin, M.; Pozo, J. L. Del; Yáñez, L.; Tilley, R.; Manzur, A.; Novo, A.; Carratalà, J.We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.Item Comparative evaluation of four rapid SARS-CoV-2 antigen detection tests using universal transport medium(2021) Weitzel, Thomas; Legarraga, Paulette; Iruretagoyena, Mirentxu; Pizarro, Gabriel; Vollrath, Valeska; Araos, Rafael; Munita, José; Porte, LorenaCorrespondenceItem Covid-19 in South America: clinical and epidemiological characteristics among 381 patients during the early phase of the pandemic in Santiago, Chile(2020) Vial, Macarena; Peters, Anne; Pérez, Inia; Spencer-Sandino, María; Barbé, Mario; Porte, Lorena; Weitzel, Thomas; Aylwin, Mabel; Vial, Pablo; Araos, Rafael; Munita, JoséBackground: Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic. Methods: We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome. Results: From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31–49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death. Conclusion: During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.Item Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocáceas gram positivas(Sociedad Chilena de Infectología, 2012) Araos, Rafael; García, Patricia; Chanqueo, Leonardo; Labarca, JaimeDaptomicina es un anti-infeccioso de reciente introducción en Chile, miembro exclusivo de una nueva familia de antimicrobianos conocida como lipopéptidos cíclicos. Tiene un mecanismo de acción único que le confiere un potente efecto bactericida sobre los microorganismos susceptibles. Su especto antimicrobiano comprende cocáceas grampositivas de importancia clínica como Staphylococcus aureus y Enterococcus spp., incluyendo cepas resistentes a antimicrobianos habituales. Está aprobada para el uso clínico en infecciones de piel y tejidos blandos y bacteriemia complicada y no complicada por S. aureus, en adultos. Estudios en curso sugieren que será una alternativa útil en otras infecciones frecuentes como osteomielitis, infecciones asociadas a dispositivos ortopédicos, infecciones asociadas a biopelículas e infecciones en hospederos inmunosuprimidos, en particular en pacientes onco-hematológicos. El principal efecto adverso asociado al uso de daptomicina es la toxicidad muscular, observándose miopatía reversible, la mayoría de las veces asintomática, en aproximadamente 3% de los pacientes que utilizan el fármaco.Publication Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression(2022) Feikin, Daniel R.; Higdon, Melissa M.; Abu-Raddad, Laith J.; Andrews, Nick; Araos, Rafael; Goldberg, Yair; Groome, Michelle J.; Huppert, Amit; O'Brien, Katherine L.; Smith, Peter G.; Wilder-Smith, Annelies; Zeger, Scott; Deloria Knoll, María; Patel, Minal K.Background: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. Methods: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1–6 months after full vaccination. Findings: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer–BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9–29·8) among people of all ages and 20·7 percentage points (10·2–36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4–41·6) in people of all ages and 32·0 percentage points (11·0–69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. Interpretation: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. Funding: Coalition for Epidemic Preparedness Innovations.Publication Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016)(2023) Martínez, José; Planet, Paul; Spencer, Maria; Rivas, Lina; Díaz, Lorena; Moustafa, Ahmed; Riquelme, Roberto; Alcalde, Manuel; Hanson, Blake; Carvajal, Lina; Rincón, Sandra; Reyes, Jinnethe; Lam, Marusella; Calderon, Juan; Araos, Rafael; García, Patricia; Arias, César; Munita, Jose M.The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCmecII and ST72-SCCmecVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America.Item Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile(2021) Jara, Alejandro; Undurraga, Eduardo; González, Cecilia; Paredes, Fabio; Fontecilla, Tomás; Jara, Gonzalo; Pizarro, Alejandra; Acevedo, Johanna; Leo, Katherinne; Leon, Francisco; Sans, Carlos; Leighton, Paulina; Suárez, Pamela; García-Escorza, Heriberto; Araos, Rafael;BACKGROUND Mass vaccination campaigns to prevent coronavirus disease 2019 (Covid-19) are occurring in many countries; estimates of vaccine effectiveness are urgently needed to support decision making. A countrywide mass vaccination campaign with the use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) was conducted in Chile starting on February 2, 2021. METHODS We used a prospective national cohort, including participants 16 years of age or older who were affiliated with the public national health care system, to assess the effectiveness of the inactivated SARS-CoV-2 vaccine with regard to preventing Covid-19 and related hospitalization, admission to the intensive care unit (ICU), and death. We estimated hazard ratios using the extension of the Cox proportional-hazards model, accounting for time-varying vaccination status. We estimated the change in the hazard ratio associated with partial immunization (≥14 days after receipt of the first dose and before receipt of the second dose) and full immunization (≥14 days after receipt of the second dose). Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. RESULTS The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons. Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of Covid-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of Covid-19–related death.Publication Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile(2022) Jara, Alejandro; Undurraga, Eduardo A.; Zubizarreta, José R.; González, Cecilia; Acevedo, Johanna; Pizarro, Alejandra; Vergara, Verónica; Soto-Marchant, Mario; Gilabert, Rosario; Flores, Juan Carlos; Suárez, Pamela; Leighton, Paulina; Eguiguren, Pablo; Ríos, Juan Carlos; Fernández, Jorge; García-Escorza, Heriberto; Araos, RafaelThe outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac’s inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5–39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6–75.2) against hospitalization and 69.0% (95% CI, 18.6–88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3–5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.Publication Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine: a large-scale prospective cohort study(2022) Jara, Alejandro; Undurraga, Eduardo A.; Zubizarreta, José R.; González, Cecilia; Pizarro, Alejandra; Acevedo, Johanna; Leo, Katherinne; Paredes, Favio; Bralic, Tomás; Vergara, Verónica; Mosso, Marcelo; León, Francisco; Parot, Ignacio; Leighton, Paulina; Suárez, Pamela; Ríos, Juan Carlos; García-Escorza, Heriberto; Araos, RafaelBackground: Vaccine protection against Covid-19 may be waning. Several countries have authorized or begun using a booster vaccine dose. Policymakers urgently need evidence of the effectiveness of additional vaccine doses against Covid-19 and its clinical spectrum for individuals with complete primary immunization schedules. Methods: We used a prospective national cohort of 11·2 million persons 16 years or older to assess the effectiveness of CoronaVac, AZD1222, or BNT162b2 vaccine boosters in individuals who completed their primary immunization schedule with CoronaVac compared to unvaccinated individuals. The study was conducted in Chile from February 2 through November 10, 2021. We used inverse probability-weighted survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in the hazard associated with complete immunization (≥14 days after the booster). Findings: We found an adjusted vaccine effectiveness against symptomatic Covid-19 of 78·8% (95% confidence interval, CI, 76·8–80·6) for a three-dose schedule with CoronaVac, 96·5% (95% CI, 96·2–96·7) for BNT162b2 booster, and 93·2% (95% CI, 92·9–93·6) for the AZD1222 booster. The adjusted vaccine effectiveness against hospitalization, ICU admission, and Covid-19 related deaths was 86·3%, 92·2%, and 86·7% for a three-dose schedule with CoronaVac, 96·1%, 96·2%, and 96·8% for the BNT162b2 booster, and 97·7%, 98·9%, and 98·1% for the AZD1222 booster. Interpretation: Our results suggest that a homologous or heterologous booster shot for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against Covid-19, including severe disease and death. However, heterologous boosters showed higher vaccine effectiveness for all outcomes, providing additional support for using a mix and match approach. Funding Information: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The research protocol was approved by the Comité Ético Científico Clínica Alemana Universidad del Desarrollo. The study was considered exempt from informed consent, no human health risks were identified. Research analysts belong to the Chilean Ministry of Health; our use of data follows Chilean law 19·628 on personal data protection.Item Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples(2020) Porte, Lorena; Legarraga, Paulette; Vollrath, Valeska; Aguilera, Ximena; Munita, José; Araos, Rafael; Pizarro, Gabriel; Vial, Pablo; Iruretagoyena, Mirentxu; Dittrich, Sabine; Weitzel, ThomasObjectives: In the context of the coronavirus disease 2019 (COVID-19) pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. This study was performed to evaluate a novel rapid antigen detection test (RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory samples. Methods: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected COVID-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real-time (RT)-PCR. Results: A total of 127 samples were included; 82 were RT-PCR-positive. The median patient age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (95% confidence interval 86.5-97.4%) and 100% (95% confidence interval 92.1-100%), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. Conclusions: The RDT evaluated in this study showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.Item Evaluation of two fluorescence immunoassays for the rapid detection of SARS-CoV-2 antigen-new tool to detect infective COVID-19 patients(2021) Porte, Lorena; Legarraga, Paulette; Iruretagoyena, Mirentxu; Vollrath, Valeska; Pizarro, Gabriel; Munita, José; Araos, Rafael; Weitzel, ThomasBackground Real-Time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) is currently the only recommended diagnostic method for SARS-CoV-2. However, rapid immunoassays for SARS-CoV-2 antigen could significantly reduce the COVID-19 burden currently weighing on laboratories around the world. Methods We evaluated the performance of two rapid fluorescence immunoassays (FIAs), SOFIA SARS Antigen FIA (Quidel Corporation, San Diego, CA, USA) and STANDARD F COVID-19 Ag FIA (SD Biosensor Inc., Gyeonggi-do, Republic of Korea), which use an automated reader. The study used 64 RT-PCR characterized clinical samples (32 positive; 32 negative), which consisted of nasopharyngeal swabs in universal transport medium. Results Of the 32 positive specimens, all from patients within 5 days of symptom onset, the Quidel and SD Biosensor assays detected 30 (93.8%) and 29 (90.6%) samples, respectively. Among the 27 samples with high viral loads (Ct ≤ 25), the two tests had a sensitivity of 100%. Specificity was 96.9% for both kits. Conclusion The high performance of the evaluated FIAs indicates a potential use as rapid and PCR-independent tools for COVID-19 diagnosis in early stages of infection. The excellent sensitivity to detect cases with viral loads above ~106 copies/mL (Ct values ≤ 25), the estimated threshold of contagiousness, suggests that the assays might serve to rapidly identify infective individuals.Item Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and Clostridium difficile(2018) Araos, Rafael; Andreatos, Nikolaos; Ugalde, Juan; Mitchell, Susan; Mylonakis, Eleftherios; D’Agata, Erika M. C.Background/Objectives Patients colonized with toxinogenic strains of Clostridium difficile have an increased risk of subsequent infection. Given the potential role of the gut microbiome in increasing the risk of C. difficile colonization, we assessed the diversity and composition of the gut microbiota among long-term care facility (LTCF) residents with advanced dementia colonized with C. difficile. Design Retrospective analysis of rectal samples collected during a prospective observational study. Setting Thirty-five nursing homes in Boston, Massachusetts. Participants Eighty-seven LTCF residents with advanced dementia. Measurements Operational taxonomic units were identified using 16S rRNA sequencing. Samples positive for C. difficile were matched to negative controls in a 1:3 ratio and assessed for differences in alpha diversity, beta diversity, and differentially abundant features. Results Clostridium difficile sequence variants were identified among 7/87 (8.04%) residents. No patient had evidence of C. difficile infection. Demographic characteristics and antimicrobial exposure were similar between the seven cases and 21 controls. The overall biodiversity among cases and controls was reduced with a median Shannon index of 3.2 (interquartile range 2.7–3.9), with no statistically significant differences between groups. The bacterial community structure was significantly different among residents with C. difficile colonization versus those without and included a predominance of Akkermansia spp., Dermabacter spp., Romboutsia spp., Meiothermus spp., Peptoclostridium spp., and Ruminococcaceae UGC 009. Conclusion LTCF residents with advanced dementia have substantial dysbiosis of their gut microbiome. Specific taxa characterized C. difficile colonization status.Item Fecal Microbiome Characteristics and the Resistome Associated With Acquisition of Multidrug-Resistant Organisms Among Elderly Subjects(Frontiers Media S.A., 2019-09) Araos, Rafael; Battaglia, Thomas; Ugalde, Juan; Rojas-Herrera, Marcelo; Blaser, Martin; D'Agata, ErikaInfections caused by multidrug-resistant organisms (MDRO) lead to considerable morbidity and mortality. The elderly population residing in nursing homes are a major reservoir of MDRO. Our objective was to characterize the fecal microbiome of 82 elderly subjects from 23 nursing homes and compare their resistome to that of healthy young persons. Comparisons of microbiome composition and the resistome between subjects who acquired MDRO or not were analyzed to characterize specific microbiome disruption indices (MDI) associated with MDRO acquisition. An approach based on both 16S rRNA amplicon and whole metagenome shotgun (WMS) sequencing data was used. The microbiome of the study cohort was substantially perturbed, with Bacteroides, Firmicutes, and Proteobacteria predominating. Compared to healthy persons, the cohort of elderly persons had an increased number, abundance, and diversity of antimicrobial resistance genes. High proportions of study subjects harbored genes for multidrug-efflux pumps (96%) and linezolid resistance (52%). Among the 302 antimicrobial resistance gene families identified in any subject, 60% were exclusively detected within the study cohort, including Class D beta-lactamase genes. Subjects who acquired MDRO or not had significant differences in bacterial taxa; Odoribacter laneus, and Akkermansia muciniphila were significantly greater among subjects who did not acquire MDRO whereas Blautia hydrogenotrophica predominated among subjects who acquired MDRO. These findings suggest that specific MDI may identify persons at high risk of acquiring MDRO.Item First wave of SARS-CoV-2 in Santiago Chile: Seroprevalence, asymptomatic infection and infection fatality rate(2022) Vial, Pablo; González, Claudia; Apablaza, Mauricio; Vial, Cecilia; Lavín, M. Estela; Araos, Rafael; Rubilar, Paola; Icaza, Gloria; Florea, Andrei; Pérez, Claudia; Concha, Paula; Bastías, Diego; Errázuriz, María Paz; Pérez, Ruth; Guzmán, Francisco; Olea, Andrea; Guzmán, Eugenio; Correa, Juan; Munita, José; Aguilera, XimenaBackground: The first wave of SARS-CoV-2 infection in Chile occurred during the cold season reaching a peak by the end of June 2020, with 80 % of the cases concentrated in its capital, Santiago. The main objective of this study was to estimate the attack rate during this first wave of SARS-CoV-2 in a large, densely populated city with more than seven million inhabitants. Since the number of confirmed cases provides biased information due to individuals’ potential self-selection, mostly related to asymptomatic patients and testing access, we measured antibodies against SARS-CoV-2 to assess infection prevalence during the first wave in the city, as well as estimate asymptomatic cases, and infection fatality ratio. To our knowledge this is one of the few population-based cross- sectional serosurvey during the first wave in a highly affected emerging country. The challenges of pandemic response in urban settings in a capital city like Santiago, with heterogeneous subpopulations and high mobility through public transportation, highlight the necessity of more accurate information regarding the first waves of new emerging diseases. Methods: From April 24 to June 21, 2020, 1326 individuals were sampled from a long-standing panel of household representatives of Santiago. Immunochromatographic assays were used to detect IgM and IgG anti-body isotypes. Results: Seroprevalence reached 6.79 % (95 %CI 5.58 %− 8.26 %) in the first 107 days of the pandemic, without significant differences among sex and age groups; this figure indicates an attack rate 2.8 times higher than the one calculated with registered cases. It also changes the fatality rate estimates, from a 2.33 % case fatality rate reported by MOH to an estimated crude 1.00 % (CI95 % 0.97–1.03) infection fatality rate (adjusted for test performance 1.66 % [CI95 % 1.61–1.71]). Most seropositive were symptomatic (81,1 %). Conclusions: Despite the high number of cases registered, mortality rates, and the stress produced over the health system, the vast majority of the people remained susceptible to potential new epidemic waves. We contribute to the understanding of the initial spread of emerging epidemic threats. Consequently, our results provide better information to design early strategies that counterattack new health challenges in urban contexts.Item Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa Treated With Ceftolozane/Tazobactam(2019) Rodríguez, Olga; Periañez, Leonor; Oliver, Antonio; Munita, José; Boté, Anna; Gasch, Oriol; Nuvials, Xavier; Dinh, Aurélien; Shaw, Robert; Lomas, José; Torres, Vicente; Castón, Juanjo; Araos, Rafael; Abbo, Lilian; Rakita, Robert; Pérez, Federico; Aitken, Samuel; Arias, Cesar; Martín, María Luisa; Colomar, Asun; Núñez, María Belén; Mensa, Josep; Martínez, José; Soriano, AlexBackground: Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible P. aeruginosa. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-P. aeruginosa considering the C/T MIC. Methods: This was a multicenter retrospective study of 90 patients with LRI caused by resistant P. aeruginosa who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. Results: The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with P. aeruginosa strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; P = .041). Multivariate analysis identified septic shock (P < .001), C/T MIC >2 mg/L (P = .045), and increasing Charlson Comorbidity Index (P = .019) as independent predictors of mortality. Conclusions: The effectiveness of C/T in P. aeruginosa LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.Item Impact of antibiotic resistance on outcomes of neutropenic cancer patients with Pseudomonas aeruginosa bacteraemia (IRONIC study): study protocol of a retrospective multicentre international study(BMJ, 2019-05) Albasanz-Puig, Adaia; Gudiol, Carlota; Parody, Rocío; Tebe, Cristian; Akova, Murat; Araos, Rafael; Bote, Anna; Brunel, Anne-Sophie; Calik, Sebnem; Drgona, Lubos; García, Estefanía; Hemmati, Philipp; Herrera, Fabián; Ibrahim, Karim; Isler, Burcu; Kanj, Souha; Kern, Winfried; Maestro de la Calle, Guillermo; Manzur, Adriana; Marin, Jorge; Márquez-Gómez, Ignacio; Martín-Dávila, Pilar; Mikulska, Malgorzata; Montejo, José Miguel; Montero, Milagros; Paz, Hugo; Morales, Isabel; Novo, Andrés; Oltolini, Chiara; Peghin, Maddalena; Del Pozo, Jose Luis; Puerta-Alcalde, Pedro; Ruiz-Camps, Isabel; Sipahi, Oguz; Tilley, Robert; Yáñez, Lucrecia; Ribeiro, Marisa; Carratalà, Jordi; IRONIC study groupIntroduction: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality. Methods and analysis: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates. Ethics and dissemination: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients' personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications.Item Isolation of Ciprofloxacin and Ceftazidime-Resistant Enterobacterales From Vegetables and River Water Is Strongly Associated With the Season and the Sample Type(2021) Díaz-Gavidia, Constanza; Rivas, Lina; Barría, Carla; García, Patricia; Alvarez, Francisca P.; González-Rocha, Gerardo; Opazo-Capurro, Andrés; Araos, Rafael; Munita, José; Cortes, Sandra; Olivares-Pacheco, Jorge; Adell, Aiko; Moreno-Switt, AndreaThe dissemination of antibiotic-resistant bacteria (ARB) from water used for crop irrigation to vegetables is poorly studied. During a year, five farmer markets in a city in Central Chile were visited, and 478 vegetable samples (parsleys, corianders, celeries, lettuces, chards, and beets) were collected. Simultaneously, 32 water samples were collected from two rivers which are used to irrigate the vegetables produced in the area. Resistant Enterobacterales were isolated and identified. Colistin resistance gene mcr-1 and extended spectrum β-lactamases (ESBL) were molecularly detected. The association of environmental factors was evaluated, with the outcomes being the presence of Enterobacterales resistant to four antibiotic families and the presence of multidrug resistance (MDR) phenotypes. Parsley, coriander, and celery showed the highest prevalence of resistant Enterobacterales (41.9% for ciprofloxacin and 18.5% for ceftazidime). A total of 155 isolates were obtained, including Escherichia coli (n=109), Citrobacter sp. (n=20), Enterobacter cloacae complex (n=8), Klebsiella pneumoniae (n=8), and Klebsiella aerogenes (n=1). Resistance to ampicillin (63.2%) and ciprofloxacin (74.2%) was most frequently found; 34.5% of the isolates showed resistance to third-generation cephalosporins, and the MDR phenotype represented 51.6% of the isolates. In two E. coli isolates (1.29%), the gene mcr-1 was found and ESBL genes were found in 23/62 isolates (37%), with bla CTX-M being the most frequently found in 20 isolates (32%). Resistant Enterobacterales isolated during the rainy season were less likely to be MDR as compared to the dry season. Understanding environmental associations represent the first step toward an improved understanding of the public health impact of ARB in vegetables and water.