MUNITA SEPULVEDA, JOSE MANUEL
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MUNITA SEPULVEDA, JOSE MANUEL
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josemunita@udd.cl
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24825037700

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A liaF Codon Deletion Abolishes Daptomycin Bactericidal Activity against Vancomycin-Resistant Enterococcus faecalis

2013 , MUNITA SEPULVEDA, JOSE MANUEL , Truc T. Tran , Lorena Diaz , Diana Panesso , Jinnethe Reyes , Barbara E. Murray , Cesar A. Arias

The genetic bases for antibiotic tolerance are obscure. Daptomycin (DAP) is a lipopeptide antibiotic with bactericidal activity against enterococci. Using time-kill assays, we provide evidence for the first time that a deletion of isoleucine in position 177 of LiaF, a member of the three-component regulatory system LiaFSR involved in the cell envelope response to antimicrobials, is directly responsible for a DAP-tolerant phenotype and is likely to negatively affect response to DAP therapy.

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Erratum for Arias et al., “A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries”

2018 , Cesar A. Arias , Jinnethe Reyes , Lina Paola Carvajal , Sandra Rincon , Lorena Diaz , Diana Panesso , Gabriel Ibarra , Rafael Rios , MUNITA SEPULVEDA, JOSE MANUEL , Mauro J. Salles , Carlos Alvarez-Moreno , Jaime Labarca , Coralith Garcia , Carlos M. Luna , Carlos Mejia-Villatoro , Jeannete Zurita , Manuel Guzman-Blanco , Eduardo Rodriguez-Noriega , Apurva Narechania , Laura J. Rojas , Paul J. Planet , George M. Weinstock , Eduardo Gotuzzo , Carlos Seas

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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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Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries

2022 , María F. Mojica , Elsa De La Cadena , Rafael Ríos , Juan Carlos García-Betancur , Lorena Díaz , Jinnethe Reyes , Cristhian Hernández-Gómez , Marcela Radice , Ana C. Gales , Paulo Castañeda Méndez , MUNITA SEPULVEDA, JOSE MANUEL , Christian José Pallares , José R. W. Martínez , María Virginia Villegas

ObjectivesIdentify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice.MethodsClinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect blaKPC, blaNDM-1, blaVIM, and blaIMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.ResultsA total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated blaPDC and ampD, associated with decreased susceptibility to TOL.ConclusionSubstitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.

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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.

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Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure

2020 , Rafael Rios , Jinnethe Reyes , Lina P. Carvajal , Sandra Rincon , Diana Panesso , Aura M. Echeverri , An Dinh , Sergios-Orestis Kolokotronis , Apurva Narechania , Truc T. Tran , MUNITA SEPULVEDA, JOSE MANUEL , Barbara E. Murray , Paul J. Planet , Cesar A. Arias , Lorena Diaz

AbstractLittle is known about the population structure of vancomycin-resistant Enterococcus faecium (VREfm) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998–2015 in 5 countries. The LATAM VREfm population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VREfm 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 VREfm and revisit the evolution of these pathogens.

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A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenonnics of Staphylococcus aureus Bacterennia in Nine Latin American Countries

2017 , Cesar A. Arias , Jinnethe Reyes , Lina Paola Carvajal , Sandra Rincon , Lorena Diaz , Diana Panesso , Gabriel Ibarra , Rafael Rios , MUNITA SEPULVEDA, JOSE MANUEL , Mauro J. Salles , Carlos Alvarez-Moreno , Jaime Labarca , Coralith Garcia , Carlos M. Luna , Carlos Mejia-Villatoro , Jeannete Zurita , Manuel Guzman-Blanco , Eduardo Rodriguez-Noriega , Apurva Narechania , Laura J. Rojas , Paul J. Planet , George M. Weinstock , Eduardo Gotuzzo , Carlos Seas

ABSTRACT Staphylococcus aureus is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185 S. aureus ) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec [SCC mec ] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCC mec IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.

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Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?

2016 , Bhavarth S. Shukla , Samuel Shelburne , Katherine Reyes , Mini Kamboj , Jessica D. Lewis , Sandra L. Rincon , Jinnethe Reyes , Lina P. Carvajal , Diana Panesso , Costi D. Sifri , Marcus J. Zervos , Eric G. Pamer , Truc T. Tran , Javier Adachi , MUNITA SEPULVEDA, JOSE MANUEL , Rodrigo Hasbun , Cesar A. Arias

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Correlation between Mutations in liaFSR of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints

2012 , MUNITA SEPULVEDA, JOSE MANUEL , Diana Panesso , Lorena Diaz , Truc T. Tran , Jinnethe Reyes , Audrey Wanger , Barbara E. Murray , Cesar A. Arias

Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system (P<0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated

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Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil

2015 , Diana Panesso , Paul J. Planet , Lorena Diaz , Jean-Emmanuel Hugonnet , Truc T. Tran , Apurva Narechania , MUNITA SEPULVEDA, JOSE MANUEL , Sandra Rincon , Lina P. Carvajal , Jinnethe Reyes , Alejandra Londoño , Hannah Smith , Robert Sebra , Gintaras Deikus , George M. Weinstock , Barbara E. Murray , Flavia Rossi , Michel Arthur , Cesar A. Arias

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