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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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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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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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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Isolation of Ciprofloxacin and Ceftazidime-Resistant Enterobacterales From Vegetables and River Water Is Strongly Associated With the Season and the Sample Type

2021 , Constanza Díaz-Gavidia , Carla Barría , RIVAS JIMENEZ, LINA MARIA , Patricia García , Francisca P. Alvarez , Gerardo González-Rocha , Andrés Opazo-Capurro , ARAOS BRALIC, RAFAEL IGNACIO , Sandra Cortes , MUNITA SEPULVEDA, JOSE MANUEL , Jorge Olivares-Pacheco , Aiko D. Adell , Andrea I. Moreno-Switt

The dissemination of antibiotic-resistant bacteria (ARB) from water used for crop irrigation to vegetables is poorly studied. During a year, five farmer markets in a city in Central Chile were visited, and 478 vegetable samples (parsleys, corianders, celeries, lettuces, chards, and beets) were collected. Simultaneously, 32 water samples were collected from two rivers which are used to irrigate the vegetables produced in the area. Resistant Enterobacterales were isolated and identified. Colistin resistance gene mcr-1 and extended spectrum β-lactamases (ESBL) were molecularly detected. The association of environmental factors was evaluated, with the outcomes being the presence of Enterobacterales resistant to four antibiotic families and the presence of multidrug resistance (MDR) phenotypes. Parsley, coriander, and celery showed the highest prevalence of resistant Enterobacterales (41.9% for ciprofloxacin and 18.5% for ceftazidime). A total of 155 isolates were obtained, including Escherichia coli (n=109), Citrobacter sp. (n=20), Enterobacter cloacae complex (n=8), Klebsiella pneumoniae (n=8), and Klebsiella aerogenes (n=1). Resistance to ampicillin (63.2%) and ciprofloxacin (74.2%) was most frequently found; 34.5% of the isolates showed resistance to third-generation cephalosporins, and the MDR phenotype represented 51.6% of the isolates. In two E. coli isolates (1.29%), the gene mcr-1 was found and ESBL genes were found in 23/62 isolates (37%), with blaCTX-M being the most frequently found in 20 isolates (32%). Resistant Enterobacterales isolated during the rainy season were less likely to be MDR as compared to the dry season. Understanding environmental associations represent the first step toward an improved understanding of the public health impact of ARB in vegetables and water.

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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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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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Mechanical and antimicrobial properties of low‐density‐polyethylene/ MgO nanocomposites

2022 , Alejandro Cament , Viviana Moreno‐Serna , Carlos Loyo , Pabla Quintana , Pablo Seura , Raúl Vallejos Baier , Rosario Benavente , María Teresa Ulloa , RIVAS JIMENEZ, LINA MARIA , Eduardo Pino , Tatiana Gómez , Paula A. Zapata

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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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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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