RIVAS JIMENEZ, LINA MARIA
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RIVAS JIMENEZ, LINA MARIA
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lrivas@udd.cl
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55921716700

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Antimicrobial nanocomposites based on biowaste eggshell derived CaO nanoparticles for potential food packaging application

2024 , Enzo Ormazábal , Viviana Moreno-Serna , Francesca A. Sepúlveda , Carlos Loyo , J. Andrés Ortiz , Francisco Melo , Maria T. Ulloa , RIVAS JIMENEZ, LINA MARIA , Teresa Corrales , Silvia Matiacevich , Paula A. Zapata

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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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A multispecies outbreak of carbapenem-resistant bacteria harboring the blaKPC gene in a non-classical transposon element

2021 , Aniela Wozniak , Cristian Figueroa , Francisco Moya-Flores , Piero Guggiana , Claudia Castillo , RIVAS JIMENEZ, LINA MARIA , Patricia C. García , MUNITA SEPULVEDA, JOSE MANUEL

Abstract Background Klebsiella pneumoniae is the most frequent KPC-producing bacteria. The blaKPC gene is frequently embedded in Tn4401 transposon, and less frequently in non-Tn4401 elements (NTEKPC) variants I-III. The first case of KPC in the UC-CHRISTUS Clinical Hospital was detected in Pseudomonas aeruginosa. Soon after this event, KPC was detected in 2 additional Pseudomonas aeruginosa, 3 Escherichia coli, 3 Enterobacter cloacae, 3 Klebsiella pneumoniae, and 1 Citrobacter freundii, isolated from 6 different patients. We aimed to elucidate the possible mechanisms of genetic transfer and dissemination of the blaKPC gene among isolates of this multispecies outbreak. A molecular epidemiology analysis of the above mentioned clinical isolates (n = 13) through Multi-Locus Sequence Typing, plasmid analysis, Pulsed-Field Gel-Electrophoresis, and Whole-genome sequencing (WGS) was performed. Results High-risk sequence types were found: K. pneumoniae ST11, P. aeruginosa ST654, and E. cloacae ST114. All enterobacterial isolates were not clonal except for 3 E. coli isolated from the same patient. WGS analysis in 6 enterobacterial isolates showed that 4 of them had blaKPC embedded in a novel variant of NTEKPC designated NTEKPC-IIe. Upstream of blaKPC gene there was a 570 pb truncated blaTEM-1 gene followed by an insertion sequence that was 84% similar to ISEc63, a 4473 bp element of the Tn3 family. Downstream the blaKPC gene there was a truncated ISKpn6 gene, and the inverted repeat right sequence of Tn4401. The ISec63-like element together with the blaKPC gene plus Tn4401 remnants were inserted in the Tra operon involved in conjugative transfer of the plasmid. This NTE was carried in a broad host-range IncN plasmid. P. aeruginosa isolates carried blaKPC gene embedded in a typical Tn4401b transposon in a different plasmid, suggesting that there was no plasmid transfer between Enterobacteriaceae and P. aeruginosa as initially hypothesized. Conclusions Most enterobacterial isolates had blaKPC embedded in the same NTEKPC-IIe element, suggesting that this multispecies KPC outbreak was due to horizontal gene transfer rather than clonal spread. This poses a greater challenge to infection control measures often directed against containment of clonal spread.

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High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study

2023 , ARAOS BRALIC, RAFAEL IGNACIO , Rachel M Smith , Ashley Styczynski , Felipe Sánchez , Lea Maureira , ACEVEDO ROMO, JOHANNA PATRICIA , Catalina Paredes , Maite González , RIVAS JIMENEZ, LINA MARIA , Maria Spencer-Sandino , Anne Peters , Ayesha Khan , Dino Sepulveda , Loreto Rojas Wettig , María Luisa Rioseco , Pedro Usedo , Pamela Rojas Soto , Laura Andrea Huidobro , Catterina Ferreccio , Benjamin J Park , Eduardo Undurraga , Erika M C D’Agata , Alejandro Jara , MUNITA SEPULVEDA, JOSE MANUEL

Abstract Background Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. Methods From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. Results A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9–50.0), 41.2% (95% CI, 37.7–44.6), 14.5% (95% CI, 12.0–16.9), and 26.3% (95% CI, 23.2–29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4–44.6), 28.9% (95% CI, 24.2–33.6), 5.6% (95% CI, 3.2–8.0), and 4.8% (95% CI, 2.6–7.0), respectively. Conclusions A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

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Colonization With Antibiotic-Resistant Gram-Negative Bacteria in Population-Based Hospital and Community Settings in Chile

2020 , ARAOS BRALIC, RAFAEL IGNACIO , Anne Peters , Felipe Sanchez , Danilo Alvares , RIVAS JIMENEZ, LINA MARIA , Maria Spencer , MARTÍNEZ SOLIS, RODRIGO , Francisco Moya , Loreto Rojas , Maria Luisa Rioseco , Pamela Rojas , Pedro Usedo , Rachel Smith , Paul Malpiedi , Benjamin J. Park , Aditya Sharma , Andrea Huidobro , Catterina Ferreccio , Erika DAgata , MUNITA SEPULVEDA, JOSE MANUEL

Background: Estimating the burden of intestinal colonization with antibiotic-resistant gram-negative bacteria (AR-GNB) is critical to understanding their global epidemiology and spread. We aimed to determine the prevalence of, and risk factors for, intestinal colonization due to AR-GNB in population-based hospital and community settings in Chile. Methods: Between December 2018 and May 2019, we enrolled randomly selected hospitalized adults in 4 tertiary-care public hospitals (Antofagasta, Santiago, Curico and Puerto Montt), and adults residing in a community-based cohort in the rural town of Molina. Following informed consent, we collected rectal swabs and epidemiological information through a standardized questionnaire. Swabs were plated onto MacConkey agar with 2 µg/mL ciprofloxacin or ceftazidime. All recovered morphotypes were identified, and antibiotic susceptibility testing was performed via disk diffusion. The primary outcome was the prevalence of colonization with fluoroquinolone (FQ)- or third-generation cephalosporin (3GC)–resistant GNB. The secondary outcome was the prevalence of colonization with multidrug-resistant (MDR) GNB, defined as GNB resistant to ≥3 antibiotic classes. Categories were not mutually exclusive. Bivariate and multivariate analyses were performed to describe risk factors for colonization with these categories. Results: In total, 775 hospitalized adults and 357 community participants were enrolled, with a median age of 60 years (IQR, 42–72) and 55 years (IQR, 48–62) years, respectively. Among hospitalized participants, the prevalence of colonization with FQ- or 3GC-resistant GNB was 47% (95% CI, 43%–50%) and 41% (95% CI, 38%–45%), respectively, whereas the prevalence of MDR-GNB colonization was 27% (95% CI, 24%–31%). In the community setting, the prevalence of colonization with either FQ-, 3GC-resistant GNB, or MDR-GNB was 40% (95% CI, 34%–45%), 29% (95% CI, 24%– 34%), and 5% (95% CI, 3%–8%), respectively. Independent risk factors for hospital MDR-GNB colonization included the hospital of admission, unit of hospitalization (intensive care units carried the highest risk), in-hospital antimicrobial exposure, comorbidities (Charlson index), and length of stay. In the community setting, recent antibiotic exposure (<3 months) predicted colonization with either FQ- or 3GC-resistant GNB, and alcohol consumption was inversely associated with MDR GNB colonization. Conclusions: A high burden of colonization with AR-GNB was observed in this sample of hospitalized and community-dwelling adults in Chile. The high burden of colonization with GNB resistant to commonly used antibiotics such as FQ and 3GC found in community dwellers, suggests that the community may be a relevant source of antibiotic resistance. Efforts to understand relatedness between resistant strains circulating in the community and the hospital are needed.Funding: NoneDisclosures: None

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Multiple clonal transmissions of clinically relevant extended-spectrum beta-lactamase–producing Escherichia coli among livestock, dogs, and wildlife in Chile

2023 , Juliette Hayer , Marília Salgado-Caxito , Andrés Opazo-Capurro , Paulina González Muñoz , Javier Millán , Ana Piñeiro , MUNITA SEPULVEDA, JOSE MANUEL , RIVAS JIMENEZ, LINA MARIA , Julio A. Benavides

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Venus antiqua Clamshell-Derived Calcium Oxide Nanoparticles for the Preparation of PLA/d-Limonene/CaO Nanocomposites with Antimicrobial Properties

2023 , Viviana Moreno-Serna , Claudio Oyarzún , Maria T. Ulloa-Flores , RIVAS JIMENEZ, LINA MARIA , Francesca Antonella Sepúlveda , Carlos Loyo , Esmeralda Lopez Toro , Paula A. Zapata

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Risk factors associated with faecal carriage of extended-spectrum cephalosporin-resistant Escherichia coli among dogs in Southeast Brazil

2021 , Marília Salgado-Caxito , Julio A. Benavides , MUNITA SEPULVEDA, JOSE MANUEL , RIVAS JIMENEZ, LINA MARIA , Patricia García , Fernando J.P. Listoni , Andrea I. Moreno-Switt , Antonio C. Paes

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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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Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa

2022 , María José Contreras-Gómez , José R. W. Martinez , RIVAS JIMENEZ, LINA MARIA , Juan A. Ugalde , Roberto Riquelme-Neira , Aniela Wozniak , Patricia García , Jorge Olivares-Pacheco , MUNITA SEPULVEDA, JOSE MANUEL , ALCALDE RICO, MANUEL

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.

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