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The Latin American Society for Immunodeficiencies Registry
(2024)
Gisela Seminario
;
Maria Edith Gonzalez-Serrano
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Carolina Sanchez Aranda
;
Anete Sevciovic Grumach
;
Gesmar Rodrigues Silva Segundo
Scopus© Citations 1 3
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Excess burden of antibiotic-resistant bloodstream infections: evidence from a multicentre retrospective cohort study in Chile, 2018–2022
(2024)
Kasim Allel
;
Anne Peters
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Hassan Haghparast-Bidgoli
;
Maria Spencer-Sandino
;
Jose Conejeros
Scopus© Citations 2 4
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Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review
(2023)
Sarah B Doernberg
;
Cesar A Arias
;
Deena R Altman
;
Ahmed Babiker
;
Helen W Boucher
<jats:title>Abstract</jats:title><jats:p>The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.</jats:p>
8Scopus© Citations 7
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Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome
(2023)
Roxane Labrosse
;
Julia I. Chu
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Myriam A. Armant
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John K. Everett
;
Danilo Pellin
<jats:title>Abstract</jats:title> <jats:p>Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.6-kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All patients were alive and well with sustained multilineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections, and bleeding diathesis was universal. Immune function was consistently improved despite subphysiologic levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity after GT, despite similar percentages of WAS protein–expressing cells and gene marking to those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), interleukin-10–producing regulatory B cells (Bregs), and transitional B cells. Thus, recovery of the Breg compartment, along with Tregs appears to be protective against development of autoimmunity after GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered at clinicaltrials.gov as #NCT01410825.</jats:p>
12Scopus© Citations 30
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Multiple clonal transmissions of clinically relevant extended-spectrum beta-lactamase–producing Escherichia coli among livestock, dogs, and wildlife in Chile
(2023)
Juliette Hayer
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Marília Salgado-Caxito
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Andrés Opazo-Capurro
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Paulina González Muñoz
;
Javier Millán
Scopus© Citations 16 1
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Head-to-head comparison of CAMPYAIR aerobic culture medium versus standard microaerophilic culture for Campylobacter isolation from clinical samples
(2023)
Arturo Levican
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Carmen Varela
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Lorena Porte
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WEITZEL, THOMAS
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Isabel Briceño
<jats:p><jats:italic>Campylobacter</jats:italic> spp. are considered the most frequent cause of acute gastroenteritis worldwide. However, outside high-income countries, its burden is poorly understood. Limited published data suggest that <jats:italic>Campylobacter</jats:italic> prevalence in low- and middle-income countries is high, but their reservoirs and age distribution are different. Culturing <jats:italic>Campylobacter</jats:italic> is expensive due to laboratory equipment and supplies needed to grow the bacterium (e.g., selective culture media, microaerophilic atmosphere, and a 42°C incubator). These requirements limit the diagnostic capacity of clinical laboratories in many resource-poor regions, leading to significant underdiagnosis and underreporting of isolation of the pathogen. CAMPYAIR, a newly developed selective differential medium, permits <jats:italic>Campylobacter</jats:italic> isolation without the need for microaerophilic incubation. The medium is supplemented with antibiotics to allow <jats:italic>Campylobacter</jats:italic> isolation in complex matrices such as human feces. The present study aims to evaluate the ability of the medium to recover <jats:italic>Campylobacter</jats:italic> from routine clinical samples. A total of 191 human stool samples were used to compare the ability of CAMPYAIR (aerobic incubation) and a commercial <jats:italic>Campylobacter</jats:italic> medium (CASA, microaerophilic incubation) to recover <jats:italic>Campylobacter</jats:italic>. All <jats:italic>Campylobacter</jats:italic> isolates were then identified by MALDI-TOF MS. CAMPYAIR showed sensitivity and specificity values of 87.5% (95% CI 47.4%–99.7%) and 100% (95% CI 98%–100%), respectively. The positive predictive value of CAMPYAIR was 100% and its negative predictive value was 99.5% (95% CI 96.7%–99.9%); Kappa Cohen coefficient was 0.93 (95% CI 0.79–1.0). The high diagnostic performance and low technical requirements of the CAMPYAIR medium could permit <jats:italic>Campylobacter</jats:italic> culture in countries with limited resources.</jats:p>
Scopus© Citations 3 1
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Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing <i>Klebsiella pneumoniae</i> 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
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Maria Spencer-Sandino
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P &lt; .001), 50.9 to 110.1 (P &lt; .001), and 4.1 to 13.3 (P &lt; .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 &lt; .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 &lt; .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
30Scopus© Citations 36
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Prognostic significance of early urinary catheterization after acute stroke: Secondary analyses of the international HeadPoST trial
(2020)
Menglu Ouyang
;
Laurent Billot
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Lili Song
;
Xia Wang
;
Christine Roffe
<jats:sec><jats:title>Background</jats:title><jats:p> An indwelling urinary catheter (IUC) is often inserted to manage bladder dysfunction, but its impact on prognosis is uncertain. We aimed to determine the association of IUC use on clinical outcomes after acute stroke in the international, multi-center, cluster crossover, Head Positioning in Acute Stroke Trial (HeadPoST). </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Data were analyzed on HeadPoST participants (n = 11,093) randomly allocated to the lying-flat or sitting-up head position. Binomial, logistic regression, hierarchical mixed models were used to determine associations of early insertion of IUC within seven days post-randomization and outcomes of death or disability (defined as “poor outcome,” scores 3–6 on the modified Rankin scale) and any urinary tract infection at 90 days with adjustment of baseline and post-randomization management covariates. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Overall, 1167 (12%) patients had an IUC, but the frequency and duration of use varied widely across patients in different regions. IUC use was more frequent in older patients, and those with vascular comorbidity, greater initial neurological impairment (on the National Institutes of Health Stroke Scale), and intracerebral hemorrhage as the underlying stroke type. IUC use was independently associated with poor outcome (adjusted odds ratio (aOR): 1.40, 95% confidence interval (CI): 1.13–1.74), but not with urinary tract infection after adjustment for antibiotic treatment and stroke severity at hospital separation (aOR: 1.13, 95% CI: 0.59–2.18). The number exposed to IUC for poor outcome was 13. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> IUC use is associated with a poor outcome after acute stroke. Further studies are required to inform appropriate use of IUC. </jats:p></jats:sec>
Scopus© Citations 4 3
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Variability in care for children with severe acute asthma in Latin America
(2020)
Nicolas Monteverde‐Fernandez
;
Franco Diaz‐Rubio
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Pablo Vásquez‐Hoyos
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Alexandre T. Rotta
;
Sebastián González‐Dambrauskas
12Scopus© Citations 5
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Immune Dysregulation Mimicking Systemic Lupus Erythematosus in a Patient With Lysinuric Protein Intolerance: Case Report and Review of the Literature
(2021)
Josefina Longeri Contreras
;
Mabel A. Ladino
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Katherine Aránguiz
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Gonzalo P. Mendez
;
Zeynep Coban-Akdemir
<jats:p>Lysinuric protein intolerance (LPI) is an inborn error of metabolism caused by defective transport of cationic amino acids in epithelial cells of intestines, kidneys and other tissues as well as non-epithelial cells including macrophages. LPI is caused by biallelic, pathogenic variants in <jats:italic>SLC7A7</jats:italic>. The clinical phenotype of LPI includes failure to thrive and multi-system disease including hematologic, neurologic, pulmonary and renal manifestations. Individual presentations are extremely variable, often leading to misdiagnosis or delayed diagnosis. Here we describe a patient that clinically presented with immune dysregulation in the setting of early-onset systemic lupus erythematosus (SLE), including renal involvement, in whom an LPI diagnosis was suspected post-mortem based on exome sequencing analysis. A review of the literature was performed to provide an overview of the clinical spectrum and immune mechanisms involved in this disease. The precise mechanism by which ineffective amino acid transport triggers systemic inflammatory features is not yet understood. However, LPI should be considered in the differential diagnosis of early-onset SLE, particularly in the absence of response to immunosuppressive therapy.</jats:p>
5Scopus© Citations 18

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