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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 , Kasim Allel , Anne Peters , José Conejeros , José R W Martínez , Maria Spencer-Sandino , Roberto Riquelme-Neira , RIVAS JIMENEZ, LINA MARIA , Pamela Rojas , Cristian Orellana Chea , Patricia García , ARAOS BRALIC, RAFAEL IGNACIO , Olivia McGovern , Twisha S Patel , Cesar A Arias , Fernanda C Lessa , Eduardo A Undurraga , MUNITA SEPULVEDA, JOSE MANUEL

Abstract 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.

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The story behind Chile's rapid rollout of COVID-19 vaccination

2021 , AGUILERA SANHUEZA, XIMENA PAZ , Adrian P. Mundt , ARAOS BRALIC, RAFAEL IGNACIO , WEITZEL, THOMAS

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Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection

2023 , Cinthya Ruiz-Tagle , Juan A. Ugalde , Rodrigo Naves , ARAOS BRALIC, RAFAEL IGNACIO , Patricia García , María Elvira Balcells

AbstractThe 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.

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Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and Clostridium difficile

2018 , ARAOS BRALIC, RAFAEL IGNACIO , Nikolaos Andreatos , Juan Ugalde , Susan Mitchell , Eleftherios Mylonakis , Erika M. C. D’Agata

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Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile

2022 , Alejandro Jara , Eduardo A. Undurraga , José R. Zubizarreta , Cecilia González , ACEVEDO ROMO, JOHANNA PATRICIA , Alejandra Pizarro , Verónica Vergara , Mario Soto-Marchant , Rosario Gilabert , Juan Carlos Flores , Pamela Suárez , Paulina Leighton , Pablo Eguiguren , Juan Carlos Ríos , Jorge Fernandez , Heriberto García-Escorza , ARAOS BRALIC, RAFAEL IGNACIO

AbstractThe 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.

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Navigating economic turmoil: Chilean businesses during COVID-19 lockdowns and vaccine rollouts

2023 , Julio A. Pertuze , José Pablo Montégu , Cecilia González , Rafael Araos , Paula Daza

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Pneumocystis en autopsias en la población general

2010 , ARAOS BRALIC, RAFAEL IGNACIO

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Predominance of Lactobacillus spp. among Patients Who Do Not Acquire Multidrug-Resistant Organisms

2016 , ARAOS BRALIC, RAFAEL IGNACIO , Albert K. Tai , Graham M. Snyder , Martin J. Blaser , Erika M. C. D'Agata

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Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile

2023 , Alejandro Jara , Cristobal Cuadrado , Eduardo A. Undurraga , Christian García , Manuel Nájera , María Paz Bertoglia , Verónica Vergara , Jorge Fernández , Heriberto García-Escorza , ARAOS BRALIC, RAFAEL IGNACIO

AbstractIn 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.

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Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors

2022 , Cristina Royo-Cebrecos , Julia Laporte-Amargós , Marta Peña , Isabel Ruiz-Camps , Pedro Puerta-Alcalde , Edson Abdala , Chiara Oltolini , Murat Akova , Miguel Montejo , Malgorzata Mikulska , Pilar Martín-Dávila , Fabian Herrera , Oriol Gasch , Lubos Drgona , Hugo Manuel Paz Morales , Anne-Sophie Brunel , Estefanía García , Burcu Isler , Winfried V. Kern , Zaira R. Palacios-Baena , Guillermo Maestro de la Calle , Maria Milagro Montero , Souha S. Kanj , Oguz R. Sipahi , Sebnem Calik , Ignacio Márquez-Gómez , Jorge I. Marin , Marisa Z. R. Gomes , Philipp Hemmatti , ARAOS BRALIC, RAFAEL IGNACIO , Maddalena Peghin , José Luis del Pozo , Lucrecia Yáñez , Robert Tilley , Adriana Manzur , Andrés Novo , Jordi Carratalà , Carlota Gudiol

Objectives: 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.