Research Output

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Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study

2022 , Minggui Wang , Michelle Earley , Liang Chen , Blake M Hanson , Yunsong Yu , Zhengyin Liu , Soraya Salcedo , Eric Cober , Lanjuan Li , Souha S Kanj , Hainv Gao , MUNITA SEPULVEDA, JOSE MANUEL , Karen Ordoñez , Greg Weston , Michael J Satlin , Sandra L Valderrama-Beltrán , Kalisvar Marimuthu , Martin E Stryjewski , Lauren Komarow , Courtney Luterbach , Steve H Marshall , Susan D Rudin , Claudia Manca , David L Paterson , Jinnethe Reyes , Maria V Villegas , Scott Evans , Carol Hill , Rebekka Arias , Keri Baum , Bettina C Fries , Yohei Doi , Robin Patel , Barry N Kreiswirth , Robert A Bonomo , Henry F Chambers , Vance G Fowler , Cesar A Arias , David van Duin , Lilian M Abbo , Deverick J Anderson , Rebekka Arias , Cesar A Arias , Keri Baum , Robert A Bonomo , Henry F Chambers , Liang Chen , Kean Lee Chew , Eric Cober , Heather R Cross , Partha Pratim De , Samit Desai , Sorabh Dhar , Valentina Di Castelnuovo , Lorena Diaz , AN Q Dinh , Yohei Doi , Michelle Earley , Brandon Eilertson , Beth Evans , Scott Evans , Vance G Fowler Jr , Bettina C Fries , Hainv Gao , Julia Garcia-Diaz , Omai B Garner , Kerryl Greenwood-Quaintance , Blake Hanson , Erica Herc , Carol Hill , Jesse T Jacob , Jianping Jiang , Robert C Kalayjian , Souha S Kanj , Keith S Kaye , Angela Kim , Lauren Komarow , Barry N Kreiswirth , Courtney Lauterbach , Lanjuan Li , Zhengyin Liu , Claudia Manca , Kalisvar Marimuthu , Steven H Marshall , Todd McCarty , Oon Tek Ng , Jose Millan Oñate Gutierrez , Karen Ordoñez , Robin Patel , David L Paterson , Anton Peleg , Jinnethe Reyes , Susan D Rudin , Robert A Salata , Soraya Salcedo , Michael J Satlin , Suzannah Schmidt-Malan , Nares Smitasin , Maria Spencer , Martin Stryjewski , Jiachun Su , Paul Ananth Tambyah , Sandra Valderrama , David van Duin , Maria Virginia Villegas Botero , Minggui Wang , Mary Waters , Greg Weston , Darren Wong , Glenn Wortmann , Yang Yang , Yunsong Yu , Fujie Zhang

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Selective digestive decontamination with oral colistin plus gentamicin for persistent bacteraemia caused by non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae in a neutropenic patient

2021 , Maria Spencer-Sandino , Roberto Riquelme-Neira , William C Shropshire , An Q Dinh , Gerardo González-Rocha , Paulina González-Muñoz , Alejandra Vera-Leiva , ARAOS BRALIC, RAFAEL IGNACIO , Blake Hanson , Cesar A Arias , MUNITA SEPULVEDA, JOSE MANUEL

Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CRKp) have become an increasing public health problem worldwide. While most CRKp around the world harbour a carbapenemase enzyme, the clinical relevance of non-carbapenemase-producing CRKp (non-CP-CRKp) is increasingly recognized. Selective digestive decontamination (SDD) has been proven successful as a decolonization strategy for patients colonized with Gram-negatives in the ICU. However, it is not regularly used to treat invasive infections. Objectives To report the use of SDD as a useful strategy for managing recalcitrant CRKp bloodstream infections. Patients and methods We present a neutropenic patient with a recalcitrant bloodstream infection with non-CP-CRKp treated with SDD. Besides, genomic analyses of five isolates of non-CP-CRKp was performed. Results After 11 days of SDD treatment with oral colistin and gentamicin, bacteraemia was successfully eradicated. Genomic analysis indicates a fully carbapenem-resistant phenotype evolved in vivo and suggests that the mechanism of carbapenem resistance in our strains relates to gene amplification of narrow-spectrum β-lactamases. Conclusions Our report highlights that SDD might be a useful strategy to manage CRKp bloodstream infections, when intestinal translocation is the likely source of the bacteraemia. In addition, the development of a resistant phenotype during therapy is worrisome as therapies directed against these organisms are likely to favour the amplification process.

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Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000–2016)

2023 , José R. W. Martínez , Paul J. Planet , Maria Spencer-Sandino , RIVAS JIMENEZ, LINA MARIA , Ahmed M. Moustafa , Lorena Díaz , Blake Hanson , RIQUELME NEIRA, ROBERTO ANDRES , ALCALDE RICO, MANUEL , Ana Quesille-Villalobos , Lina P. Carvajal , Sandra Rincón , Jinnethe Reyes , Marusella Lam , Patricia García , ARAOS BRALIC, RAFAEL IGNACIO , César A. Arias , Juan F. Calderon , MUNITA SEPULVEDA, JOSE MANUEL , Adriana E. Rosato

Methicillin-resistant Staphylococcus aureus (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.

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Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America

2022 , Betsy E Castro , Rafael Rios , Lina P Carvajal , Mónica L Vargas , Mónica P Cala , Lizeth León , Blake Hanson , An Q Dinh , Oscar Ortega-Recalde , Carlos Seas , MUNITA SEPULVEDA, JOSE MANUEL , Cesar A Arias , Sandra Rincon , Jinnethe Reyes , Sandra Patricia Díaz Ortiz

Abstract Background 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. Objective To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. Methods 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. Results 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. Conclusions 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.

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Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

2023 , Jinnethe Reyes , Lauren Komarow , Liang Chen , Lizhao Ge , Blake M Hanson , Eric Cober , Erica Herc , Thamer Alenazi , Keith S Kaye , Julia Garcia-Diaz , Lanjuan Li , Souha S Kanj , Zhengyin Liu , Jose M Oñate , Robert A Salata , Kalisvar Marimuthu , Hainv Gao , Zhiyong Zong , Sandra L Valderrama-Beltrán , Yunsong Yu , Paul Tambyah , Gregory Weston , Soraya Salcedo , Lillian M Abbo , Qing Xie , Karen Ordoñez , Minggui Wang , Martin E Stryjewski , Jose M Munita , David L Paterson , Scott Evans , Carol Hill , Keri Baum , Robert A Bonomo , Barry N Kreiswirth , Maria Virginia Villegas , Robin Patel , Cesar A Arias , Henry F Chambers , Vance G Fowler , Yohei Doi , David van Duin , Michael J Satlin , Jinnethe Reyes , Lauren Komarow , Liang Chen , Lizhao Ge , Blake Hanson , Eric Cober , Erica Herc , Thamer Alenazi , Keith Kaye , Julia Garcia-Diaz , Lanjuan Li , Souha Kanj , Zhengyin Liu , Jose Oñate , Robert Salata , Kalisvar Marimuthu , Hainv Gao , Zhiyong Zong , Sandra Valderrama-Beltrán , Yunsong Yu , Paul Tambyah , Gregory Weston , Soraya Salcedo , Lillian Abbo , Qing Xie , Karen Ordoñez , Minggui Wang , Martin Stryjewski , MUNITA SEPULVEDA, JOSE MANUEL , David Paterson , Scott Evans , Carol Hill , Keri Baum , Robert Bonomo , Barry Kreiswirth , Maria Virginia Villegas , Robin Patel , Cesar Arias , Henry Chambers , Vance Fowler , Yohei Doi , David van Duin , Michael Satlin

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Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter Baumannii Among Patients From Different Global Regions

2023 , Minggui Wang , Lizhao Ge , Liang Chen , Lauren Komarow , Blake Hanson , Jinnethe Reyes , Eric Cober , Thamer Alenazi , Zhiyong Zong , Qing Xie , Zhengyin Liu , Lanjuan Li , Yunsong Yu , Hainv Gao , Souha S Kanj , Jairo Figueroa , Erica Herc , Ezequiel Cordova , Gregory Weston , Paul Ananth Tambyah , Julia Garcia-Diaz , Keith S Kaye , Sorabh Dhar , MUNITA SEPULVEDA, JOSE MANUEL , Robert A Salata , Samuel Vilchez , Martin E Stryjewski , Maria Virginia Villegas Botero , Alina Iovleva , Scott R Evans , Keri Baum , Carol Hill , Barry N Kreiswirth , Robin Patel , David L Paterson , Cesar A Arias , Robert A Bonomo , Henry F Chambers , Vance G Fowler , Michael J Satlin , David van Duin , Yohei Doi , Souha S Kanj , Fujie Zhang , Judith J Lok , Robert A Salata , Martin Stryjewski , Valentina Di Castelnuovo , Jose Millan Oñate Gutierrez , Eric Cober , Susan Richter , Deverick J Anderson , Beth Evans , Carol Hill , Heather R Cross , Keri Baum , Rebekka Arias , Vance G Fowler , Karen Ordoñez , Jesse T Jaco , Linghua L , Barry N Kreiswirth , Claudia Manca , Liang Chen , Samit Desai , SALVAJ CARRERA, ERICA HELENA , Ezequiel Cordov , Maria Riosec , Samuel Vilche , Marisa L Sanche , Sandra Valderram , Jairo Figuero , Cesar A Arias , An Q Dinh , Diane Panesso , Kirsten Rydell , Truc T Tra , Fupin Hu , Jiachun Su , Jianping Jiang , Minggui Wang , Xiaogang Xu , Yang Yan , Maria Spence , Thamer Alenazi , Robert A Bonomo , Steven H Marshall , Susan D Rudin , Charles Huskins , Kerry Greenwood-Quaintance , Robin Patel , Suzannah Schmidt-Malan , Sara Revolinski , Glenn Wortmann , Robert C Kalayjian , Gregory Weston , Belinda Ostrowsky , Gopi Patel , Daniel Eiras , Angela Kim , Julia Garcia-Diaz , Soraya Salcedo , John J Farrell , Zhengyin Liu , Andrew Henderson , David L Paterso , Qing Xie , Keith S Kaye , Hainv Gao , Yunsong Y , Mary Water , Bettina C Fries , Brandon Eilertson , Kalisvar Marimuthu , Oon Tek Ng , Partha Pratim De , Kean Lee Chew , Nares Smitasin , Paul Ananth Tambyah , Jason C Gallagher , Anton Peleg , Marcel Leroi , Lanjuan Li , Yonghong Xiao , Lauren Komarow , Lizhao Ge , Scott Evans , Todd McCarty , Henry F Chambers , Omai B Garner , Lilian M Abbo , David van Duin , Ebbing Lautenbach , Jennifer H Han , Yohei Doi , Darren Wong , Blake Hanson , Jinnethe Reyes , Maria Virginia Villegas Botero , Lorena Dia , Federico Perez , Ritu Banerjee , Sorabh Dhar , Michael J Satlin , Lars F Westblade , Zhiyong Zong

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. Results Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. Conclusions CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.