Molecular epidemiology of the Chilean-Cordobes clone in South America and the contribution of heavy metal resistance in the ability of MRSA to disseminate and prevail

Project Title

Partner Organisations

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Internal ID

1171805

Principal Investigator

MUNITA SEPULVEDA, JOSE MANUEL

Type

basic research

Status

TERMINADO

Start Date

2017

Investigators

Juan Ugalde

Publications

Now showing 1 - 10 of 13

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Covid-19 in South America: clinical and epidemiological characteristics among 381 patients during the early phase of the pandemic in Santiago, Chile
(2020)
Macarena R. Vial
;
Anne Peters
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Inia Pérez
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María Spencer-Sandino
;
Mario Barbé
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31–49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.</jats:p> </jats:sec>
1 3Scopus© Citations 15
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Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000–2016)
(2023)
José R. W. Martínez
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Paul J. Planet
;
Maria Spencer-Sandino
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RIVAS JIMENEZ, LINA MARIA
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Ahmed M. Moustafa
<jats:p> Methicillin-resistant <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. </jats:p>
4Scopus© Citations 12
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Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections
(2019)
German A. Contreras
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MUNITA SEPULVEDA, JOSE MANUEL
;
Cesar A. Arias
1Scopus© Citations 36
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A One Health - One World initiative to control antibiotic resistance: A Chile - Sweden collaboration
(2019)
Jaime R. Cabrera-Pardo
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Rolf Lood
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Klas Udekwu
;
Gerardo Gonzalez-Rocha
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MUNITA SEPULVEDA, JOSE MANUEL
1Scopus© Citations 23
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Correction for Khan et al., “A Multicenter Study To Evaluate Ceftaroline Breakpoints: Performance in an Area with High Prevalence of Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Lineage”
(2021)
Ayesha Khan
;
Lina M. Rivas
;
Maria Spencer
;
Rodrigo Martinez
;
Marusella Lam
1 1
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Multiomics characterization of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America
(2022)
Betsy E Castro
;
Rafael Rios
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Lina P Carvajal
;
Mónica L Vargas
;
Mónica P Cala
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.</jats:p> </jats:sec>
1 3Scopus© Citations 8
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Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure
(2020)
Rafael Rios
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Jinnethe Reyes
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Lina P. Carvajal
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Sandra Rincon
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Diana Panesso
<jats:title>Abstract</jats:title><jats:p>Little is known about the population structure of vancomycin-resistant <jats:italic>Enterococcus faecium</jats:italic> (VR<jats:italic>Efm</jats:italic>) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VR<jats:italic>Efm</jats:italic> recovered from 1998–2015 in 5 countries. The LATAM VR<jats:italic>Efm</jats:italic> population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VR<jats:italic>Efm</jats:italic> by including 285 genomes from 36 countries spanning from 1946 to 2017. In contrast to previous studies, our results show an early branching of animal related isolates and a further split of clinical isolates into two sub-clades within clade A. The overall phylogenomic structure of clade A was highly dependent on recombination (54% of the genome) and the split between clades A and B was estimated to have occurred more than 2,765 years ago. Furthermore, our molecular clock calculations suggest the branching of animal isolates and clinical clades occurred ~502 years ago whereas the split within the clinical clade occurred ~302 years ago (previous studies showed a more recent split between clinical an animal branches around ~74 years ago). By including isolates from Latin America, we present novel insights into the population structure of VR<jats:italic>Efm</jats:italic> and revisit the evolution of these pathogens.</jats:p>
1 1Scopus© Citations 59
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Managing All the Genotypic Knowledge: Approach to a Septic Patient Colonized by Different Enterobacteriales with Unique Carbapenemases
(2019)
Stacy C. Park
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Alexander M. Wailan
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Katie E. Barry
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Kasi Vegesana
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Joanne Carroll
<jats:p> The recent development of new antimicrobials active against carbapenemase-producing <jats:italic>Enterobacteriales</jats:italic> (CPE) has brought new hope for the treatment of infections due to these organisms. However, the evolving epidemiology of bacteria with carbapenemases may complicate management, as providers are faced with treating patients colonized by bacteria producing multiple carbapenemases. </jats:p>
1Scopus© Citations 8
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Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile
(2021)
IRURETAGOYENA BRUCE, MIRENTXU INES
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Macarena R. Vial
;
Maria Spencer-Sandino
;
Pablo Gaete
;
Anne Peters
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The overall seroprevalence at the end of the study period was 24% (95% CI20.2–28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding’s impact on the risk of reinfection are warranted.</jats:p> </jats:sec>
1Scopus© Citations 21 2
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Phenotypic and Genotypic Characterization of Macrolide, Lincosamide and Streptogramin B Resistance among Clinical Methicillin-Resistant Staphylococcus aureus Isolates in Chile
(2022)
Mario Quezada-Aguiluz
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Alejandro Aguayo-Reyes
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Cinthia Carrasco
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Daniela Mejías
;
Pamela Saavedra
<jats:p>Macrolides, lincosamides, and type B streptogramins (MLSB) are important therapeutic options to treat methicillin-resistant Staphylococcus aureus (MRSA) infections; however, resistance to these antibiotics has been emerging. In Chile, data on the MLSB resistance phenotypes are scarce in both community-(CA) and hospital-acquired (HA) MRSA isolates. Antimicrobial susceptibility to MLSB was determined for sixty-eight non-repetitive isolates of each HA-(32) and CA-MRSA (36). Detection of SCCmec elements, ermA, ermB, ermC, and msrA genes was performed by PCR. The predominant clones were SCCmec I-ST5 (HA-MRSA) and type IVc-ST8 (CA-MRSA). Most of the HA-MRSA isolates (97%) showed resistance to clindamycin, erythromycin, azithromycin, and clarithromycin. Among CA-MRSA isolates, 28% were resistant to erythromycin, azithromycin, and 25% to clarithromycin. All isolates were susceptible to linezolid, vancomycin, daptomycin and trimethoprim/sulfamethoxazole, and over 97% to rifampicin. The ermA gene was amplified in 88% of HA-MRSA and 17% of CA-MRSA isolates (p < 0.001). The ermC gene was detected in 6% of HA-SARM and none of CA-SARM isolates, whereas the msrA gene was only amplified in 22% of CA-MRSA (p < 0.005). Our results demonstrate the prevalence of the cMLSB resistance phenotype in all HA-MRSA isolates in Chile, with the ermA being the predominant gene identified among these isolates.</jats:p>
3Scopus© Citations 10

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