Browsing by Author "Araos Bralic, Rafael Ignacio"
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Publication Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis(2023) Allel, Kasim; Peters, Anne Sophie; Conejeros, José; Martínez, José; Spencer, Maria; Riquelme, Roberto; Rivas Jiménez, Lina María; Rojas, Pamela; Orellana, Cristian; García, Patricia; Araos Bralic, Rafael Ignacio; McGovern, Olivia; Patel, Twisha; Arias, Cesar; Lessa, Fernanda; Undurraga, Eduardo; Munita, Jose M.Background: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. Methods: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. Results: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum β-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. Conclusions: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.Publication BugBuster: a novel automatic and reproducible workflow for metagenomic data analysis(2025) Fuentes, Francisco; Curiqueo, Carolina; Araos Bralic, Rafael Ignacio; Ugalde, JuanPhages are the most abundant biological entities on the planet, and they play an important role in controlling density, diversity, and network interactions among bacterial communities through predation and gene transfer. To date, a variety of bacteriophage identification tools have been developed that differ in the phage mining strategies used, input files requested, and results produced. However, new users attempting bacteriophage analysis can struggle to select the best methods and interpret the variety of results produced. Here, we present MetaPhage, a comprehensive reads-to-report pipeline that streamlines the use of multiple phage miners and generates an exhaustive report. The report both summarizes and visualizes the key findings and enables further exploration of key results via interactive filterable tables. The pipeline is implemented in Nextflow, a widely adopted workflow manager that enables an optimized parallelization of tasks in different locations, from local server to the cloud; this ensures reproducible results from containerized packages. MetaPhage is designed to enable scalability and reproducibility; also, it can be easily expanded to include new miners and methods as they are developed in this continuously growing field. MetaPhage is freely available under a GPL-3.0 license at https://github.com/MattiaPandolfoVR/MetaPhage. IMPORTANCE Bacteriophages (viruses that infect bacteria) are the most abundant biological entities on earth and are increasingly studied as members of the resident microbiota community in many environments, from oceans to soils and the human gut. Their identification is of great importance to better understand complex bacterial dynamics and microbial ecosystem function. A variety of metagenome bacteriophage identification tools have been developed that differ in the phage mining strategies used, input files requested, and results produced. To facilitate the management and the execution of such a complex workflow, we developed MetaPhage (MP), a comprehensive reads-to-report pipeline that streamlines the use of multiple phage miners and generates an exhaustive report. The pipeline is implemented in Nextflow, a widely adopted workflow manager that enables an optimized parallelization of tasks. MetaPhage is designed to enable scalability and reproducibility and offers an installation-free, dependency-free, and conflict-free workflow execution.Publication Colonization with antibiotic resistant bacteria in communities and hospitals across six countries, including Bangladesh, Botswana, Chile, Guatemala, India, and Kenya(2025) Parra, Gemma; Lautenbach, Ebbing; Mosepele, Mosepele; Mannathoko, Naledi; Gross, Robert; Call, Douglas; Ramay, Brooke; Omulo, Sylvia; Girish, C P; Bhatnagar, Tarun; Chowdhury, Fahmida; Syeda Mah-E-Muneer; Araos Bralic, Rafael Ignacio; Munita, Jose M.; Acevedo, Johanna; Mahon, Garrett; Smith, Rachel; Styczynski, AshleyThe recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek® 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0-99). Colonization with ESCrE in hospitals was high in all sites (range 34-84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.Publication Conocimiento y conductas asociadas al uso comunitario de antimicrobianos en adultos en Santiago de Chile(2022) Ross Pérez, Patricio; Barrera Quiroz, Javier; Ivys Palma, Paula; Radic Sierra, Catalina; Bellinghausen Scott, Matías; Ruiz-Tagle, Reyes, Matías; Blanc Arteaga, Josefina; Kline, Madeleine; Araos Bralic, Rafael IgnacioIntroducción: El uso de antimicrobianos se asocia a efectos late rales como alergias, reacciones adversas específicas y emergencia de resistencia antimicrobiana. Resulta fundamental una comunicación de riesgo efectiva a la población general sobre su utilidad y potenciales problemas. Experiencias internacionales revelan un bajo grado de conocimiento en la comunidad en países sin políticas educativas dirigidas, lo que mejora tras su implementación; a nivel regional y nacional existen escasas publicaciones al respecto. Objetivo: Describir el grado de conocimiento y conductas sobre el uso de antimicrobianos en adultos de Santiago de Chile. Métodos: Estudio transversal realiza do mediante una encuesta a adultos en Santiago de Chile, evaluando cuatro aspectos sobre antimicrobianos: conocimiento, uso reciente, conductas sobre su uso y nociones sobre resistencia antimicrobiana. Resultados: Se encuestaron 300 personas entre 18 y 81 años (tres fueron descartadas posteriormente), siendo 75% de ellas menores de 45 años. Un 65% de los encuestados cree que los antibióticos antimicrobianos son activos frente a virus, 51% cree que sirven para tratar el resfrío común y 32% los ha utilizado sin receta. Un 51% ha escuchado el término resistencia antimicrobiana y 33% conoce su definición correcta. Conclusión: El conocimiento sobre la utilidad y problemas de los antimicrobianos en población chilena es deficiente, lo que podría favorecer su uso inapropiado.Publication Cost-effectiveness of strategies using preventive interventions to protect infants in Chile from respiratory syncytial virus(2025) Bolanos, Rafael; Araos Bralic, Rafael Ignacio; Gonzalez, Cecilia; Sepulveda, Dino; Falconi, Juan; Averin, Ahuva; Atwood, Mark; Quinn, Erin; Law, Amy; Mendes, DianaBackground: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI; RSV-LRTI) among infants in Chile; young infants and infants born prematurely are at greatest risk. Research design and methods: A cohort model was developed to evaluate cost-effectiveness of strategies preventing RSV-LRTI in infants. Using the model, we calculated the economically justifiable price (EJP) of maternal RSVpreF vaccination (MV) versus no intervention and then evaluated the cost-effectiveness of MV (cost/dose assumed at EJP) with complementary use of monoclonal antibody nirsevimab for unprotected infants (MV+N) versus nirsevimab alone (NA) to prevent RSV-LRTI. Nirsevimab published price was $260.00; costs/prices reported in 2023 US$. Results: NA yielded 20,247 cases (hospital: 3,773, emergency ward: 16,474) and $57.2 million (M) in total costs (medical: $6.3 M, intervention: $48.7 M, indirect: $2.2 M). MV+N yielded 23,906 cases (hospital: 3,137, emergency ward: 20,769) and $28.7 M in costs (medical: $4.8 M, intervention: $21.7 M [RSVpreF assumed $75.77/dose; nirsevimab procured $260.00/dose], indirect: $2.2 M). With costs lower by $28.4 M and increased quality-adjusted life-years, MV+N would be cost-saving versus NA. Conclusions: RSVpreF vaccination among pregnant women along with nirsevimab for unprotected infants in Chile would be the most efficient use of resources, yielding substantial cost savings compared to use of nirsevimab alone. Trial registration: ClinicalTrials.gov NCT04424316 NCT03979313.Publication Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia(2022) Albasanz-Puig, Adaia; Durà-Miralles, Xavier; Laporte-Amargós, Júlia; Mussetti, Alberto; Ruiz-Camps, Isabel; Puerta-Alcalde, Pedro ; Abdala, Edson ; Oltolini, Chiara; Akova, Murat; Montejo ,José Miguel; Malgorzata, Mikulska; Martín-Dávila, Pilar; Herrera, Fabián; Gasch, Oriol; Drgona, Lubos; Paz Morales, Hugo Manuel; Brunel, Anne-Sophie; García, Estefanía; Isler, Burcu; Kern, Winfried V.; Retamar-Gentil, Pilar; Aguado, José María; Montero, Milagros; Kanj, Souha S.; Sipahi, Oguz R.; Calik, Sebnem; Márquez-Gómez, Ignacio; Marín, Jorge I.; Gomes, Marisa Z.R.; Hemmati, Philipp; Araos Bralic, Rafael Ignacio; Peghin, Magdalena; Pozo, José Luis del; Yáñez, Lucrecia; Tilley, Robert; Manzur, Adriana; Novo, Andres; Pallarès, Natàlia; Bergas, Alba; Carratalà, Jordi; Gudiol, Carlota; The Ironic Study GroupTo assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.Publication Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study(2023) Jara, Alejandro; Undurraga, Eduardo; Flores, Juan; Zubizarreta, José; González, Cecilia; Pizarro, Alejandra; Ortuño, Duniel; Acevedo, Johanna; Leo, Katherinne; Paredes, Fabio; Bralic , Tomás; Vergara, Verónica; Leon, Francisco; Parot, Ignacio; Leighton, Paulina; Suárez, Pamela; Rios, Juan; García, Heriberto; Rafael Araos; Araos Bralic, Rafael IgnacioBackground: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP)Publication Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile(2023) Jara, Alejandro; Cuadrado, Cristobal; Undurraga, Eduardo; García , Christian; Nájera, Manuel; Bertoglia, María; Vergara, Verónica; Fernández , Jorge; García, Heriberto; Araos Bralic, Rafael IgnacioIn light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2-89.9) against ICU admissions and 90.5% (95%CI 89.4-91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting. A la luz de la actual pandemia de COVID-19 y la aparición de nuevas variantes del SARS-CoV-2, es fundamental comprender la eficacia de varios regímenes de vacunación de refuerzo. En Chile, utilizando una cohorte nacional prospectiva de 3,75 millones de personas de 20 años o más, evaluamos la efectividad contra las admisiones a unidades de cuidados intensivos (UCI) relacionadas con COVID-19 y la muerte de segundas dosis de refuerzo basadas en ARNm para cuatro dosis diferentes de tres dosis. regímenes: serie primaria BNT162b2 seguida de un refuerzo homólogo, y serie primaria CoronaVac seguida de un refuerzo de ARNm, un refuerzo homólogo y un refuerzo de ChAdOx-1. Estimamos la efectividad de la vacuna semanalmente del 14 de febrero al 15 de agosto de 2022, determinando los índices de riesgo de inmunización frente a no vacunación, teniendo en cuenta los factores de confusión relevantes. La eficacia global ajustada de una segunda inyección de refuerzo de ARNm es del 88,2% (IC del 95%, 86,2-89,9) frente a los ingresos en la UCI y del 90,5% (IC del 95%, 89,4-91,4) frente a la muerte. La eficacia de la vacuna muestra una leve disminución en todos los regímenes y resultados, probablemente relacionada con la introducción de los sublinajes Omicron BA.4 y BA.5 y la disminución de la inmunidad. Según nuestros hallazgos, es posible que las personas no necesiten refuerzos adicionales durante al menos 6 meses después de recibir una segunda inyección de refuerzo de ARNm en este entorno.Publication Geographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes(2025) Martínez, Jose; Alcalde, Manuel; Jara, Estefanía; Reyes, Jinnethe; Carvajal, Lina; Rincon, Sandra; Ríos, Rafael; Diaz, Lorena; Quesille, Ana; Riquelme, Roberto; Rivas Jiménez, Lina María; Moustafa, Ahmed; Hanson, Blake; Undurraga, Eduardo; Olivares, Jorge; García, Patricia; Araos Bralic, Rafael Ignacio; Planet, Paul; Arias, César; Munita, Jose M.El Staphylococcus aureus resistente a la meticilina (SARM) es una importante amenaza para la salud pública. La propagación global del SARM se caracteriza por sucesivas oleadas de clones epidémicos que dominan regiones geográficas específicas. Se cree que la adquisición de genes que codifican la resistencia a metales pesados (GMMP) es una característica clave en la divergencia geográfica del SARM. Sin embargo, la relación causa-efecto entre la presencia de GMMP y la divergencia de los clones de SARM aún no se ha dilucidado. En este estudio, evaluamos el papel que los GMMP pudieron haber desempeñado en la divergencia evolutiva del linaje ST5-SCC mec I del SARM en Latinoamérica. Realizamos una caracterización genómica de 113 aislamientos clínicos de SARM de seis centros de salud latinoamericanos, incluyendo 53 aislamientos recolectados en dos ciudades de Chile (Santiago y Concepción). Encontramos un plásmido (pSCL4752) que alberga genes de resistencia al arsénico, cadmio y mercurio en el 65% ( n = 71) de los aislados ST5-SCC mec I. También observamos una divergencia geográfica asociada a la presencia de pSCL4752 en aislados chilenos, con una mayor frecuencia en aislados de Concepción (88%) en comparación con Santiago (29%). Curiosamente, un análisis de reloj molecular reveló que esta divergencia se produjo tras el terremoto y tsunami de magnitud 8,8 Mw que azotó la zona de Concepción en 2010. Además, nuestros resultados demuestran que la presencia de pSCL4752 puede ser beneficiosa o perjudicial para los aislados ST5-SCC mec I, dependiendo de la disponibilidad ambiental de estos metales pesados. Nuestros resultados sugieren que la divergencia del linaje ST5-SCC mec I MRSA en América Latina podría haber sido fomentada por desastres ambientales e influenciada por la presencia/ausencia de HMRG albergados en un plásmido. IMPORTANCIA El Staphylococcus aureus resistente a la meticilina (MRSA) es una de las principales causas de infecciones potencialmente mortales en todo el mundo y una creciente preocupación para la salud pública. El aumento de bacterias resistentes a los antibióticos, como el MRSA, a menudo está vinculado a adaptaciones genéticas que mejoran su supervivencia. Nuestra investigación arroja luz sobre cómo los cambios ambientales, como los desencadenados por un desastre natural, pueden influir en la evolución y la propagación geográfica de un linaje de MRSA altamente resistente en América Latina. Identificamos un plásmido que porta genes de resistencia al arsénico, cadmio y mercurio, el cual se asoció con la divergencia geográfica del ST5-SCC mec.Se ha identificado un linaje de SARM con diferencias notables en su prevalencia entre las regiones afectadas por un gran terremoto y tsunami. Al vincular los eventos ambientales con la evolución del patógeno, nuestro estudio destaca el papel de las presiones ecológicas en la propagación del SARM. Estos hallazgos subrayan la necesidad de integrar el monitoreo ambiental en las estrategias de salud pública para comprender mejor el desafío global de la resistencia a los antimicrobianos.Publication High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study(2023) Araos Bralic, Rafael Ignacio; Smith, Rachel; Styczynski, Ashley; Sánchez, Felipe; Acevedo, Johanna; Maureira, Lea; Paredes, Catalina; González, Maite; Rivas Jiménez, Lina María; Spencer, Maria; Peters, Anne Sophie; Khan, Ayesha; Sepulveda, Dino; Rojas, Loreto; Rioseco, María; Usedo, Pedro; Rojas, Pamela; Huidobro, Laura; Ferreccio, Catterina; Park, Benjamin; Undurraga, Eduardo; D'Agata, Erika; Jara, Alejandro; Munita, Jose M.Background: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. Methods: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. Results: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. Conclusions: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.Publication Multispecies emergence of dual blaKPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile(2025) Quesille, Ana; Solar, Camila; Martínez, Jose; Rivas Jiménez, Lina María; Quiroz, Valeria; González, Ana; Riquelme, Roberto; Ugalde, Juan; Peters, Anne; Ortega, Oscar; Araos Bralic, Rafael Ignacio; García, Patricia; Lebreton, Francois; Munita, Jose M.; Diaz, LorenaCarbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor blaKPC and blaNDM and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring blaKPC and blaNDM. Species corresponded to Escherichia coli (n = 6), Klebsiella pneumoniae (n = 2), Klebsiella oxytoca (n = 2), and Citrobacter freundii (n = 1). Dual CP-CRE isolates exhibited resistance to all tested β-lactams except for cefiderocol. The blaKPC and blaNDM encoding genes were located on independent plasmids. Platforms harboring blaKPC were diverse and included IncN, IncF, and IncFIB plasmids. In contrast, blaNDM-7 was only found on fairly conserved IncX3 plasmids. We report that a rapid increase of CP-CRE in Chile, alongside with the emergence of multiple bacterial species of CP-CRE co-harboring blaKPC-2/3 and blaNDM-7, underscores a critical public health challenge. Our data suggest that the dissemination of blaNDM-7 was predominantly facilitated by IncX3 plasmids, whereas the spread of blaKPC involved multiple plasmid backbones. Active surveillance and genomic monitoring are critical to inform public policy and curtail the spread of these highly resistant pathogens.Publication Navigating economic turmoil: Chilean businesses during COVID-19 lockdowns and vaccine rollouts(2024) Pertuze, Julio A.; Montégu, José Pablo; González, Cecilia; Araos Bralic, Rafael Ignacio; Daza, PaulaObjectives: This study evaluates the effects of COVID-19 lockdowns, differentiated by their stringency, on the sales of Chilean businesses across various size categories and industries throughout 2020 and 2021. It also explores the role of the vaccination campaign and the implementation of the Mobility Pass in mitigating the negative economic effects of stringent containment measures. Methods: The study uses administrative data from the Chilean Internal Revenue Service (SII), examining sales across different business sizes and industries, from March 2020 to December 2021. Through an econometric analysis, we estimate the effects of lockdowns on business sales during two distinct periods: initial reliance on dynamic non-pharmaceutical interventions (NPIs) pre-vaccine, and a subsequent stage characterized by high vaccine uptake and reduced NPI stringency. Results: Lockdowns significantly reduced sales across all business sizes and most industries during the first period, with microenterprises and certain service sectors experiencing the highest decline. The national vaccination campaign and the introduction of the Mobility Pass in the second period appears to have mitigated the negative effects of lockdowns, primarily benefiting micro and small firms. Conclusions: The study highlights the trade-offs between health and economic outcomes during the pandemic, stressing the importance to alleviate mobility restrictions post-vaccine rollout to ease the economic strain on businesses. The findings call for targeted support measures for MSMEs and vulnerable industries affected by NPIs.Publication Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors(2022) Royo-Cebrecos, Cristina; Laporte-Amargós, Julia; Peña, Marta; Ruiz-Camps, Isabel; Puerta-Alcalde, Pedro; Abdala, Edson; Oltolini, Chiara; Akova, Murat; Montejo, Miguel; Mikulska, Malgorzata; Martín-Dávila, Pilar; Herrera, Fabian; Gasch, Oriol; Drgona, Lubos; Paz Morales, Hugo Manuel; Brunel, Anne-Sophie; García, Estefanía; Isler, Burcu; Kern, Winfried V.; Palacios-Baena, Zaira R.; Maestro de la Calle, Guillermo; Montero, Maria Milagro; Kanj, Souha S.; Sipahi, Oguz R.; Calik, Sebnem; Márquez-Gómez, Ignacio; Marin, Jorge I.; Gomes, Marisa Z.R.; Hemmatti, Philipp; Araos Bralic, Rafael Ignacio; Peghin, Maddalena; Pozo, José Luis del; Yáñez, Lucrecia; Tilley, Robert; Manzur, Adriana; Novo, Andrés; Carratalà, Jordi; Gudiol, Carlota; Ironic study groupObjectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.Publication Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy(2024) Royo, Cristina; Laporte, Julia; Peña, Marta; Ruiz, Isabel; Garcia, Carolina; Abdala, Edson; Oltolini, Chiara; Akova, Murat; Montejo, Miguel; Mikulska, Malgorzata; Martín, Pilar; Herrera, Fabián; Gasch, Oriol; Drgona, Lubos; Paz, Hugo; Brunel, Anne; García, Estefanía; Isler, Burcu; Kern, Winfried; Palacios, Zaira; Maestr de la Calle, Guillermo; Montero, Maria; Kanj, Souha; Sipahi, Oguz; Calik, Sebnem; Márquez, Ignacio; Marin, Jorge; Gomes, Marisa; Hemmatii, Philipp; Araos Bralic, Rafael Ignacio; Peghin, Maddalena; Del Pozo, Jose; Yáñez, Lucrecia; Tilley, Robert; Manzur, Adriana; Novo, Andrés; Carratalà, Jordi; Gudiol, Carlota; IRONIC Study GroupThis large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.Publication Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection(2023) Ruiz‑Tagle, Cinthya; Ugalde, Juan; Naves, Rodrigo; Araos Bralic, Rafael Ignacio; García, Patricia; Balcells, MaríaThe upper respiratory tract is an obliged pathway for respiratory pathogens and a healthy microbiota may support the host's mucosal immunity preventing infection. We analyzed the nasopharyngeal microbiome in tuberculosis household contacts (HHCs) and its association with latent tuberculosis infection (TBI). A prospective cohort of HHCs was established and latent TBI status was assessed by serial interferon-γ release assay (IGRA). Nasopharyngeal swabs collected at baseline were processed for 16S rRNA gene sequencing. The 82 participants included in the analysis were classified as: (a) non-TBI [IGRA negative at baseline and follow-up, no active TB (n = 31)], (b) pre-TBI [IGRA negative at baseline but converted to IGRA positive or developed active TB at follow-up (n = 16)], and (c) TBI [IGRA positive at enrollment (n = 35)]. Predominant phyla were Actinobacteriota, Proteobacteria, Firmicutes and Bacteroidota. TBI group had a lower alpha diversity compared to non-TBI (padj = 0.04) and pre-TBI (padj = 0.04). Only TBI and non-TBI had beta diversity differences (padj = 0.035). Core microbiomes' had unique genera, and genus showed differential abundance among groups. HHCs with established latent TBI showed reduced nasopharyngeal microbial diversity with distinctive taxonomical composition. Whether a pre-existing microbiome feature favors, are a consequence, or protects against Mycobacterium tuberculosis needs further investigation.Publication Retrospective study on disparities in time-to-treatment by health insurance system in Chilean breast cancer patients(2025) Acevedo, Johanna; Ip, Teresa; Maureira, Lea; Sanchez, Cesar; Osorio, Claudia; Carvajal, Claudia; Rafael Araos; Araos Bralic, Rafael Ignacio; Letelier, Hernan; Acevedo, Francisco; Merino, TomasIntroduction: Breast cancer is the most common malignancy in the Americas, and the second leading cause of cancer death. Disparities in the time to treatment can significantly impact patient outcomes and typically affect lower socioeconomic individuals and/or ethnic minorities. Our study sought to evaluate disparities in time to treatment at three health institutions in Chile according to their type of health insurance (public or private). Methods: Our study analyzed a database of breast cancer patients diagnosed between 2017 and 2018. Analyses included descriptive statistics and a linear regression model that incorporated clinical and demographic variables. Additionally, using a proportional risks model, we analyzed the association between clinical variables and mortality. Results: Public health insurance (National Health Fund, FONASA) was associated with longer time-to-treatment and extended treatment times versus private health insurance (Social Security Institutions, ISAPRE; p < 0.0001). As expected, a more advanced stage at diagnosis was associated with lower survival. Our proportional risks model found that age was a predictor of breast cancer mortality in stage II patients. Also, total treatment time significantly increased the risk of breast cancer mortality in stage I patients. Conversely, total treatment time did not affect mortality on stages II or III. Conclusions: We found significant disparities in the time to treatment of Chilean breast cancer patients using FONASA versus private ISAPRE. FONASA patients experience delays in the initiation of treatment and longer total treatment times compared to their private insurance counterparts. Finally, longer time-to-treatment was associated with more advanced stages and increased mortality. INTRODUCCIÓN El cáncer de mama es la neoplasia más frecuente y la segunda causa de muerte por cáncer en el continente americano. Diferencias en los tiempos de espera al tratamiento típicamente afectan a individuos de bajo nivel socioeconómico y minorías étnicas, impactando también el pronóstico y la sobrevida. Este estudio evaluó las diferencias en tiempos de espera al tratamiento en relación al tipo de sistema de salud de los pacientes en tres instituciones de salud en Chile. MÉTODOS Se analizó una base de datos de pacientes de cáncer de mama diagnosticados entre 2017 y 2018. El análisis incluyó estadística descriptiva y un modelo de regresión lineal que consideró variables clínico-demográficas. Además la asociación entre variables clínicas y mortalidad se evaluó a través de un análisis de riesgos proporcionales RESULTADOS El sistema público de salud (Fondo Nacional de Salud, FONASA) se asoció a tiempos de espera al tratamiento más largos y tiempos totales de tratamientos más prolongados en comparación con el sistema privado (Instituciones de Salud Previsional, ISAPRES; p < 0,0001). Etapas más avanzadas al diagnóstico se asociaron a menor sobrevida. El modelo de riesgos proporcionales demostró que la edad es un predictor de mortalidad de cáncer de mama en pacientes en etapa II. Además, el tiempo total de tratamiento aumentó significativamente el riesgo de mortalidad por cáncer de mama en pacientes en etapa I. En contraste, el tiempo total de tratamiento no afectó la mortalidad en etapas II ni III. CONCLUSIONES Se encontraron diferencias significativas en el tiempo de espera al tratamiento entre pacientes Chilenas de cáncer de mama usuarias de FONASA e ISAPRES. Las pacientes de FONASA experimentaron demoras en el inicio de sus tratamientos y tiempos totales de tratamiento más prolongados en comparación a usuarias del sistema privado. Por último, tiempos de espera al tratamiento más extensos se asociaron a etapas más avanzadas y mayor mortalidad.Publication Routes of importation and spatial dynamics of SARS-CoV-2 variants during localized interventions in Chile(2024) Gutierrez, Bernardo; L -H Tsui, Joseph; Pullano, Giulia; Mazzoli, Mattia; Inward, Rhys P D; Bajaj, Sumali; Evans Pena, Rosario; Busch-Moreno, Simon; Suchard, Marc A.; Pybus, Oliver G.; Dunner, Alejandra; Puentes, Rodrigo; Fernandez, Jorge; Araos Bralic, Rafael Ignacio; Ferres, Leo; Colizza, Vittoria; Kraemer, Moritz U.G.Human mobility is strongly associated with the spread of SARS-CoV-2 via air travel on an international scale and with population mixing and the number of people moving between locations on a local scale. However, these conclusions are drawn mostly from observations in the context of the global north where international and domestic connectivity is heavily influenced by the air travel network; scenarios where land-based mobility can also dominate viral spread remain understudied. Furthermore, research on the effects of nonpharmaceutical interventions (NPIs) has mostly focused on national- or regional-scale implementations, leaving gaps in our understanding of the potential benefits of implementing NPIs at higher granularity. Here, we use Chile as a model to explore the role of human mobility on disease spread within the global south; the country implemented a systematic genomic surveillance program and NPIs at a very high spatial granularity. We combine viral genomic data, anonymized human mobility data from mobile phones and official records of international travelers entering the country to characterize the routes of importation of different variants, the relative contributions of airport and land border importations, and the real-time impact of the country’s mobility network on the diffusion of SARS-CoV-2. The introduction of variants which are dominant in neighboring countries (and not detected through airport genomic surveillance) is predicted by land border crossings and not by air travelers, and the strength of connectivity between comunas (Chile’s lowest administrative divisions) predicts the time of arrival of imported lineages to new locations. A higher stringency of local NPIs was also associated with fewer domestic viral importations. Our analysis sheds light on the drivers of emerging respiratory infectious disease spread outside of air travel and on the consequences of disrupting regular movement patterns at lower spatial scales.Item Virus Zika en un nuevo mundo(2016) Vial, Pablo; Araos Bralic, Rafael IgnacioDesde 1947, en que fue descubierto en Uganda (África), el virus Zika ha ido expandiendo su rango geográfico siguiendo una dirección de occidente a oriente: primero en diversos países africanos, luego en los años sesenta en Asia, y posteriormente Oceanía (Micronesia, 2007; Polinesia Francesa 2013). El año 2014 se registró un brote en Isla de Pascua, que se contuvo en pocas semanas; la infección fue confirmada en 50-60 habitantes1. En mayo de 2015 se confirmaron los primeros casos de virus Zika de transmisión autóctona en Brasil2. Lo que hemos presenciado desde entonces es la llegada y la expansión de un nuevo virus en un continente con el que no había tenido contacto previo y cuya población de 953 millones de habitantes carecía por completo de inmunidad. América ha tenido varias veces esta experiencia en los últimos 500 años, y algunas epidemias tuvieron consecuencias desastrosas para sus habitantes nativos (viruela, sarampión, influenza, fiebre amarilla). La travesía del virus para llegar a Brasil es descrita en una reciente carta de Didier Musso, y hay evidencia que sugiere que actualmente se encuentra en Cabo Verde, cerca de su lugar de nacimiento, con lo que habría completado la vuelta al mundo.