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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Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae 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 , Maria Spencer-Sandino , Roberto Riquelme-Neira , RIVAS JIMENEZ, LINA MARIA , Pamela Rojas , Cristian Orellana Chea , Patricia García , ARAOS BRALIC, RAFAEL IGNACIO , Olivia McGovern , Twisha S Patel , Cesar A Arias , Fernanda C Lessa , Eduardo A Undurraga , MUNITA SEPULVEDA, JOSE MANUEL

Abstract Background 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. Methods 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. Results Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .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 < .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 < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. Conclusions 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.

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Enterococcal Endocarditis: Can We Win the War?

2012 , MUNITA SEPULVEDA, JOSE MANUEL , Cesar A. Arias , Barbara E. Murray

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Mechanisms of Antibiotic Resistance

2016 , MUNITA SEPULVEDA, JOSE MANUEL , Cesar A. Arias , Indira T. Kudva , Qijing Zhang

ABSTRACT Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.

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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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Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA

2022 , Truc T Tran , Nicolo L Cabrera , Anne J Gonzales-Luna , Travis J Carlson , Faris Alnezary , William R Miller , Aki Sakurai , An Q Dinh , Kirsten Rydell , Rafael Rios , Lorena Diaz , Blake M Hanson , MUNITA SEPULVEDA, JOSE MANUEL , Claudia Pedroza , Samuel A Shelburne , Samuel L Aitken , Kevin W Garey , Ryan Dillon , Laura Puzniak , Cesar A Arias

Abstract Background Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

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Respuesta inmunitaria al SARS-CoV-2 y factores asociados previo a la vacunación, en personal de salud de atención primaria en una comuna de Santiago, Chile

2022 , OLEA NORMANDIN, ANDREA MARIA , Elena Pedroni , HIRMAS ADAUY, MACARENA SOLEDAD , MATUTE WILLEMSEM, MARIA ISABEL , IRURETAGOYENA BRUCE, MIRENTXU INES , MUNITA SEPULVEDA, JOSE MANUEL , GONZALEZ WIEDMAIER, CLAUDIA MARTA , María Inés Gómez , Manuel Nájera

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In Vivo Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa Arising by AmpC- and Non-AmpC-Mediated Pathways

2018 , Erik Skoglund , Henrietta Abodakpi , Rafael Rios , Lorena Diaz , Elsa De La Cadena , An Q. Dinh , Javier Ardila , William R. Miller , MUNITA SEPULVEDA, JOSE MANUEL , Cesar A. Arias , Vincent H. Tam , Truc T. Tran

Two pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa were isolated from 2 patients after exposure to β-lactams. The genetic basis of ceftolozane/tazobactam resistance was evaluated, and β-lactam-resistant mechanisms were assessed by phenotypic assays. Whole genome sequencing identified mutations in AmpC including the mutation (V213A) and a deletion of 7 amino acids (P210–G216) in the Ω-loop. Phenotypic assays showed that ceftolozane/tazobactam resistance in the strain with AmpCV213A variant was associated with increased β-lactamase hydrolysis activity. On the other hand, the deletion of 7 amino acids in the Ω-loop of AmpC did not display enhanced β-lactamase activity. Resistance to ceftolozane/tazobactam in P. aeruginosa is associated with changes in AmpC; however, the apparent loss of β-lactamase activity in AmpC∆7 suggests that non-AmpC mechanisms could play an important role in resistance to β-lactam/β-lactamase inhibitor combinations.

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Community acquired infections with methicillin resistant strains of Staphylococcus aureus. Report of five cases

2008 , MUNITA SEPULVEDA, JOSE MANUEL , Noriega Ricalde, Luis Miguel , González, Patricia , Hormazábal, Juan Carlos , Pinto, Consuelo , Magdalena Canals , THOMPSON MOYA, LUIS ADALBERTO , Marcotti, Alejandra , Pérez, Jorge , Ibáñez, Daniel , Araya, Pamela , Canals, Claudio , VIAL CLARO, PABLO AGUSTIN

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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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Creación del primer biorrepositorio nacional de bacterias multirresistentes disponible para el estudio de la resistencia bacteriana en Chile

2022 , Patricia García , RIVAS JIMENEZ, LINA MARIA , Anne Peters , Paola Henríquez , Loriana Castillo , Vijna Illesca , Andrea Maripani , Juan Moreno , Margareta Mühlhauser , PORTE TORRE, LORENA ISABEL , María Luisa Rioseco , Pamela Rojas , Francisco Silva , Patricio Suazo , MUNITA SEPULVEDA, JOSE MANUEL

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