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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2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 2016 2016 2015 2015 0 0 2 2 4 4 6 6 8 8 10 10 12 12 14 14 16 16 18 18 20 20
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Transmission of gram-negative antibiotic-resistant bacteria following differing exposure to antibiotic-resistance reservoirs in a rural community: a modelling study for bloodstream infections

2022 , Kasim Allel , Lara Goscé , ARAOS BRALIC, RAFAEL IGNACIO , Daniel Toro , Catterina Ferreccio , MUNITA SEPULVEDA, JOSE MANUEL , Eduardo A. Undurraga , Jasmina Panovska-Griffiths

AbstractExposure to community reservoirs of gram-negative antibiotic-resistant bacteria (GN-ARB) genes poses substantial health risks to individuals, complicating potential infections. Transmission networks and population dynamics remain unclear, particularly in resource-poor communities. We use a dynamic compartment model to assess GN-ARB transmission quantitatively, including the susceptible, colonised, infected, and removed populations at the community-hospital interface. We used two side streams to distinguish between individuals at high- and low-risk exposure to community ARB reservoirs. The model was calibrated using data from a cross-sectional cohort study (N = 357) in Chile and supplemented by existing literature. Most individuals acquired ARB from the community reservoirs (98%) rather than the hospital. High exposure to GN-ARB reservoirs was associated with 17% and 16% greater prevalence for GN-ARB carriage in the hospital and community settings, respectively. The higher exposure has led to 16% more infections and attributed mortality. Our results highlight the need for early-stage identification and testing capability of bloodstream infections caused by GN-ARB through a faster response at the community level, where most GN-ARB are likely to be acquired. Increasing treatment rates for individuals colonised or infected by GN-ARB and controlling the exposure to antibiotic consumption and GN-ARB reservoirs, is crucial to curve GN-ABR transmission.

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Dissecting the Mechanisms of Linezolid Resistance in a Drosophila melanogaster Infection Model of Staphylococcus aureus

2013 , Lorena Diaz , Dimitrios P. Kontoyiannis , Diana Panesso , Nathaniel D. Albert , Kavindra V. Singh , Truc T. Tran , MUNITA SEPULVEDA, JOSE MANUEL , Barbara E. Murray , Cesar A. Arias

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Gram-Positive Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group

2017 , Sarah B. Doernberg , Thomas P. Lodise , Joshua T. Thaden , MUNITA SEPULVEDA, JOSE MANUEL , Sara E. Cosgrove , Cesar A. Arias , Helen W. Boucher , G. Ralph Corey , Franklin D. Lowy , Barbara Murray , Loren G. Miller , Thomas L. Holland

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Comparative In Vitro Activity of Ceftolozane/Tazobactam against Clinical Isolates of Pseudomonas aeruginosa and Enterobacterales from Five Latin American Countries

2022 , Juan Carlos García-Betancur , Elsa De La Cadena , María F. Mojica , Cristhian Hernández-Gómez , Adriana Correa , Marcela A. Radice , Paulo Castañeda-Méndez , Diego A. Jaime-Villalon , Ana C. Gales , MUNITA SEPULVEDA, JOSE MANUEL , María Virginia Villegas

Background: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known β-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. Methods: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. Results: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. Conclusions: these results show that C/T is an active β-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales.

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ESBL-Producing Escherichia coli Carrying CTX-M Genes Circulating among Livestock, Dogs, and Wild Mammals in Small-Scale Farms of Central Chile

2021 , Julio A. Benavides , Marília Salgado-Caxito , Andrés Opazo-Capurro , Paulina González Muñoz , Ana Piñeiro , Macarena Otto Medina , RIVAS JIMENEZ, LINA MARIA , MUNITA SEPULVEDA, JOSE MANUEL , Javier Millán

Antibiotic-resistant bacteria of critical importance for global health such as extended-spectrum beta-lactamases-producing (ESBL)-Escherichia coli have been detected in livestock, dogs, and wildlife worldwide. However, the dynamics of ESBL-E. coli between these animals remains poorly understood, particularly in small-scale farms of low and middle-income countries where contact between species can be frequent. We compared the prevalence of fecal carriage of ESBL-E. coli among 332 livestock (207 cows, 15 pigs, 60 horses, 40 sheep, 6 goats, 4 chickens), 82 dogs, and wildlife including 131 European rabbits, 30 rodents, and 12 Andean foxes sharing territory in peri-urban localities of central Chile. The prevalence was lower in livestock (3.0%) and wildlife (0.5%) compared to dogs (24%). Among 47 ESBL-E. coli isolates recovered, CTX-M-group 1 was the main ESBL genotype identified, followed by CTX-M-groups 2, 9, 8, and 25. ERIC-PCR showed no cluster of E. coli clones by either host species nor locality. To our knowledge, this is the first report of ESBL-E. coli among sheep, cattle, dogs, and rodents of Chile, confirming their fecal carriage among domestic and wild animals in small-scale farms. The high prevalence of ESBL-E. coli in dogs encourages further investigation on their role as potential reservoirs of this bacteria in agricultural settings.

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Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin

2024 , Stephanie L. Egge , Samie A. Rizvi , Shelby R. Simar , ALCALDE RICO, MANUEL , JOSE RODRIGO WALDEMAR MARTINEZ SOLIS , Blake M. Hanson , An Q. Dinh , Rodrigo P. Baptista , Truc T. Tran , Samuel A. Shelburne , MUNITA SEPULVEDA, JOSE MANUEL , Cesar A. Arias , Morgan Hakki , William R. Miller , Ryan K. Shields

ABSTRACT The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR , pirS , pirA , piuA , or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates ( n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

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Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa

2024 , Katherine D. Soto , ALCALDE RICO, MANUEL , UGALDE, JUAN ANTONIO , Jorge Olivares Pacheco , Valeria Quiroz , Bárbara Brito , RIVAS JIMENEZ, LINA MARIA , MUNITA SEPULVEDA, JOSE MANUEL , GARCÍA CEBALLOS, PATRICIA , Aniela Wozniak

IntroductionCeftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum β-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible.MethodsAntimicrobial susceptibility was determined through agar dilution and broth microdilution, while blaPER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of blaPER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. ResultsTwenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried blaPER. One isolate carried blaPER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their blaPER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of blaPER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the in vitro evolved isolate. DiscussionPER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other β-lactams.

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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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A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player

2022 , EZQUER, EDUARDO FERNANDO , María Elena Quintanilla , Paola Morales , Daniela Santapau , MUNITA SEPULVEDA, JOSE MANUEL , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Francisco Moya-Flores , Yedy Israel

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Innate gut microbiota predisposes to high alcohol consumption

2021 , EZQUER, EDUARDO FERNANDO , Maria Elena Quintanilla , Francisco Moya‐Flores , Paola Morales , MUNITA SEPULVEDA, JOSE MANUEL , OLIVARES, MARIA BELEN , Glauben Landskron , Marcela A. Hermoso , EZQUER, EDUARDO MARCELO , Mario Herrera‐Marschitz , Yedy Israel

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