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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
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
Scopus© Citations 10 2
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Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing <i>Klebsiella pneumoniae</i> 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
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P &lt; .001), 50.9 to 110.1 (P &lt; .001), and 4.1 to 13.3 (P &lt; .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 &lt; .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 &lt; .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
30Scopus© Citations 36
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Acquisition of resistance to ceftazidime-avibactam during infection treatment in Pseudomonas aeruginosa through D179Y mutation in one of two blaKPC-2 gene copies without losing carbapenem resistance
(2022-09)
García, Patricia
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Brito, Bárbara
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ALCALDE RICO, MANUEL
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MUNITA SEPULVEDA, JOSE MANUEL
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Martínez, José R.W.
Scopus© Citations 13 2
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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
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RIVAS JIMENEZ, LINA MARIA
;
Patricia García
;
Francisca P. Alvarez
<jats:p>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 <jats:italic>mcr-1</jats:italic> 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 <jats:italic>Escherichia coli</jats:italic> (<jats:italic>n</jats:italic>=109), <jats:italic>Citrobacter</jats:italic> sp. (<jats:italic>n</jats:italic>=20), <jats:italic>Enterobacter cloacae</jats:italic> complex (<jats:italic>n</jats:italic>=8), <jats:italic>Klebsiella pneumoniae</jats:italic> (<jats:italic>n</jats:italic>=8), and <jats:italic>Klebsiella aerogenes</jats:italic> (<jats:italic>n</jats:italic>=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 <jats:italic>E. coli</jats:italic> isolates (1.29%), the gene <jats:italic>mcr-1</jats:italic> was found and ESBL genes were found in 23/62 isolates (37%), with <jats:italic>bla</jats:italic><jats:sub>CTX-M</jats:sub> 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.</jats:p>
1Scopus© Citations 28
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Higher Prevalence of Extended-Spectrum Cephalosporin-Resistant Enterobacterales in Dogs Attended for Enteric Viruses in Brazil Before and After Treatment with Cephalosporins
(2021)
Marília Salgado-Caxito
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Andrea I. Moreno-Switt
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Antonio Carlos Paes
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Carlos Shiva
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MUNITA SEPULVEDA, JOSE MANUEL
<jats:p>The extensive use of antibiotics is a leading cause for the emergence and spread of antimicrobial resistance (AMR) among dogs. However, the impact of using antibiotics to treat viral infections on AMR remains unknown. In this study, we compared the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) between dogs with a suspected infection of canine parvovirus (CPV) and canine distemper (CDV) before and after treatment with third-generation cephalosporins. We found a higher prevalence of ESCR-E faecal carriage in dogs suspected of CPV (37%) and CDV (15%) compared to dogs with noninfectious pathologies (9%) even prior to the start of their treatment. A 7-day course of ceftriaxone or ceftiofur administrated to CPV and CDV-suspected dogs substantially increased their ESCR-E faecal carriage during treatment (85% for CPV and 57% for CDV), and 4 weeks after the treatment ended (89% for CPV and 60% for CDV) when dogs were back in their households. Most of the observed resistance was carried by ESCR-E. coli carrying blaCTX-M genes. Our results suggest the need to optimize prophylactic antibiotic therapy in dogs treated for a suspected viral infection to prevent ESCR-E emergence and spread in the community.</jats:p>
5Scopus© Citations 15
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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
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MUNITA SEPULVEDA, JOSE MANUEL
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RIVAS JIMENEZ, LINA MARIA
;
Patricia García
Scopus© Citations 21 2
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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
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RIVAS JIMENEZ, LINA MARIA
;
Juan A. Ugalde
;
Roberto Riquelme-Neira
<jats:p>Carbapenem-resistant <jats:italic>Pseudomonas aeruginosa</jats:italic> (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 <jats:italic>P. aeruginosa</jats:italic> 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.</jats:p>
Scopus© Citations 2 1
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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
<jats:sec><jats:title>Objectives</jats:title><jats:p>Identify molecular mechanisms responsible for the <jats:italic>in vitro</jats:italic> non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of <jats:italic>Pseudomonas aeruginosa</jats:italic> from five Latin American countries collected before the introduction of TOL into the clinical practice.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Clinical isolates of <jats:italic>P. aeruginosa</jats:italic> (<jats:italic>n</jats:italic> = 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 <jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>NDM-1</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>VIM</jats:sub>, and <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A 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 <jats:italic>bla</jats:italic><jats:sub>PDC</jats:sub> and <jats:italic>ampD</jats:italic>, associated with decreased susceptibility to TOL.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Substitutions 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.</jats:p></jats:sec>
5Scopus© Citations 14
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Real-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase-Producing Carbapenem-Resistant Pseudomonas aeruginosa
(2022)
RIVAS JIMENEZ, LINA MARIA
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Manuel Alcalde-Rico
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José R. W. Martínez
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María Victoria Moreno
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Pamela Rojas
<jats:p> Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenem-resistant <jats:named-content content-type="genus-species">Pseudomonas aeruginosa</jats:named-content> (non-CP-CR-PA). Accurate, precise, and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions. </jats:p>
19Scopus© Citations 2
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Fecal Microbiome Characteristics and the Resistome Associated With Acquisition of Multidrug-Resistant Organisms Among Elderly Subjects
(2019)
ARAOS BRALIC, RAFAEL IGNACIO
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Thomas Battaglia
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Juan A. Ugalde
;
Marcelo Rojas-Herrera
;
Martin J. Blaser
Scopus© Citations 14 2

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