Person: Araos Bralic, Rafael Ignacio
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Araos Bralic
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Rafael Ignacio
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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 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 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 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 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 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 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 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 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.