High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis

Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric pa...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Current microbiology 2022-11, Vol.79 (11), p.353-353, Article 353
Hauptverfasser: Gutiérrez-Santana, Juan C., Gerónimo-Gallegos, Armando, Martínez-Corona, Mónica B., López-López, Marisol, Toscano-Garibay, Julia D., Cuevas-Schacht, Francisco, Coria-Jiménez, Victor R.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 353
container_issue 11
container_start_page 353
container_title Current microbiology
container_volume 79
creator Gutiérrez-Santana, Juan C.
Gerónimo-Gallegos, Armando
Martínez-Corona, Mónica B.
López-López, Marisol
Toscano-Garibay, Julia D.
Cuevas-Schacht, Francisco
Coria-Jiménez, Victor R.
description Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015–2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and “antibiotic resistance crisis” worsens.
doi_str_mv 10.1007/s00284-022-03048-4
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2723160314</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2723160314</sourcerecordid><originalsourceid>FETCH-LOGICAL-c282t-cd41e7f0063124671b5b798f238e51728f25ae6c4565038f1bb4e6e7ae808193</originalsourceid><addsrcrecordid>eNp9kE1P3DAQhi1EJZZt_0BPlrj0Ehh_JHaOaMuXhNQKcXed7GTXKOuAJwH239fLIiFx4DQzmvd9NfMw9lPAqQAwZwQgrS5AygIUaFvoAzYTWuWxrsUhm4HSqrBVKY7YMdEDgJA1iBn7dx1Wa37nRyQ-dPzidcRI4Rn7Lf-dplVxhxRo9HHkfwmn5bAZoifuMe9CHMjzEPliHfplwshfwrjmiy2NoeWXoUlD9n5n3zrfE_54r3N2f3lxv7gubv9c3SzOb4tWWjkW7VILNB1ApYTUlRFN2ZjadlJZLIWRuSs9Vq0uqxKU7UTTaKzQeLRgRa3m7Nc-9jENTxPS6DaBWux7H3GYyEkjlahAZSZzdvJJ-jBMKebjdipptJH1LlDuVW1-gxJ27jGFjU9bJ8DtmLs9c5eZuzfmbhet9ibK4rjC9BH9hes_HICDcw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2722747299</pqid></control><display><type>article</type><title>High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis</title><source>SpringerLink Journals - AutoHoldings</source><creator>Gutiérrez-Santana, Juan C. ; Gerónimo-Gallegos, Armando ; Martínez-Corona, Mónica B. ; López-López, Marisol ; Toscano-Garibay, Julia D. ; Cuevas-Schacht, Francisco ; Coria-Jiménez, Victor R.</creator><creatorcontrib>Gutiérrez-Santana, Juan C. ; Gerónimo-Gallegos, Armando ; Martínez-Corona, Mónica B. ; López-López, Marisol ; Toscano-Garibay, Julia D. ; Cuevas-Schacht, Francisco ; Coria-Jiménez, Victor R.</creatorcontrib><description>Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015–2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and “antibiotic resistance crisis” worsens.</description><identifier>ISSN: 0343-8651</identifier><identifier>EISSN: 1432-0991</identifier><identifier>DOI: 10.1007/s00284-022-03048-4</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Amikacin ; Antibiotic resistance ; Antibiotics ; Antiinfectives and antibacterials ; Biomedical and Life Sciences ; Biotechnology ; Ceftazidime ; Children ; Cross-infection ; Cystic fibrosis ; Drug resistance ; Eradication ; Genotyping ; Global health ; Life Sciences ; Microbiology ; Multidrug resistance ; Patients ; Pediatrics ; Polymerase chain reaction ; Pseudomonas aeruginosa ; Public health ; Random amplified polymorphic DNA ; Strains (organisms)</subject><ispartof>Current microbiology, 2022-11, Vol.79 (11), p.353-353, Article 353</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c282t-cd41e7f0063124671b5b798f238e51728f25ae6c4565038f1bb4e6e7ae808193</citedby><cites>FETCH-LOGICAL-c282t-cd41e7f0063124671b5b798f238e51728f25ae6c4565038f1bb4e6e7ae808193</cites><orcidid>0000-0002-3975-7305</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00284-022-03048-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00284-022-03048-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Gutiérrez-Santana, Juan C.</creatorcontrib><creatorcontrib>Gerónimo-Gallegos, Armando</creatorcontrib><creatorcontrib>Martínez-Corona, Mónica B.</creatorcontrib><creatorcontrib>López-López, Marisol</creatorcontrib><creatorcontrib>Toscano-Garibay, Julia D.</creatorcontrib><creatorcontrib>Cuevas-Schacht, Francisco</creatorcontrib><creatorcontrib>Coria-Jiménez, Victor R.</creatorcontrib><title>High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis</title><title>Current microbiology</title><addtitle>Curr Microbiol</addtitle><description>Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015–2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and “antibiotic resistance crisis” worsens.</description><subject>Amikacin</subject><subject>Antibiotic resistance</subject><subject>Antibiotics</subject><subject>Antiinfectives and antibacterials</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Ceftazidime</subject><subject>Children</subject><subject>Cross-infection</subject><subject>Cystic fibrosis</subject><subject>Drug resistance</subject><subject>Eradication</subject><subject>Genotyping</subject><subject>Global health</subject><subject>Life Sciences</subject><subject>Microbiology</subject><subject>Multidrug resistance</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Pseudomonas aeruginosa</subject><subject>Public health</subject><subject>Random amplified polymorphic DNA</subject><subject>Strains (organisms)</subject><issn>0343-8651</issn><issn>1432-0991</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kE1P3DAQhi1EJZZt_0BPlrj0Ehh_JHaOaMuXhNQKcXed7GTXKOuAJwH239fLIiFx4DQzmvd9NfMw9lPAqQAwZwQgrS5AygIUaFvoAzYTWuWxrsUhm4HSqrBVKY7YMdEDgJA1iBn7dx1Wa37nRyQ-dPzidcRI4Rn7Lf-dplVxhxRo9HHkfwmn5bAZoifuMe9CHMjzEPliHfplwshfwrjmiy2NoeWXoUlD9n5n3zrfE_54r3N2f3lxv7gubv9c3SzOb4tWWjkW7VILNB1ApYTUlRFN2ZjadlJZLIWRuSs9Vq0uqxKU7UTTaKzQeLRgRa3m7Nc-9jENTxPS6DaBWux7H3GYyEkjlahAZSZzdvJJ-jBMKebjdipptJH1LlDuVW1-gxJ27jGFjU9bJ8DtmLs9c5eZuzfmbhet9ibK4rjC9BH9hes_HICDcw</recordid><startdate>20221101</startdate><enddate>20221101</enddate><creator>Gutiérrez-Santana, Juan C.</creator><creator>Gerónimo-Gallegos, Armando</creator><creator>Martínez-Corona, Mónica B.</creator><creator>López-López, Marisol</creator><creator>Toscano-Garibay, Julia D.</creator><creator>Cuevas-Schacht, Francisco</creator><creator>Coria-Jiménez, Victor R.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3975-7305</orcidid></search><sort><creationdate>20221101</creationdate><title>High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis</title><author>Gutiérrez-Santana, Juan C. ; Gerónimo-Gallegos, Armando ; Martínez-Corona, Mónica B. ; López-López, Marisol ; Toscano-Garibay, Julia D. ; Cuevas-Schacht, Francisco ; Coria-Jiménez, Victor R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c282t-cd41e7f0063124671b5b798f238e51728f25ae6c4565038f1bb4e6e7ae808193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amikacin</topic><topic>Antibiotic resistance</topic><topic>Antibiotics</topic><topic>Antiinfectives and antibacterials</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Ceftazidime</topic><topic>Children</topic><topic>Cross-infection</topic><topic>Cystic fibrosis</topic><topic>Drug resistance</topic><topic>Eradication</topic><topic>Genotyping</topic><topic>Global health</topic><topic>Life Sciences</topic><topic>Microbiology</topic><topic>Multidrug resistance</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Pseudomonas aeruginosa</topic><topic>Public health</topic><topic>Random amplified polymorphic DNA</topic><topic>Strains (organisms)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gutiérrez-Santana, Juan C.</creatorcontrib><creatorcontrib>Gerónimo-Gallegos, Armando</creatorcontrib><creatorcontrib>Martínez-Corona, Mónica B.</creatorcontrib><creatorcontrib>López-López, Marisol</creatorcontrib><creatorcontrib>Toscano-Garibay, Julia D.</creatorcontrib><creatorcontrib>Cuevas-Schacht, Francisco</creatorcontrib><creatorcontrib>Coria-Jiménez, Victor R.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Current microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gutiérrez-Santana, Juan C.</au><au>Gerónimo-Gallegos, Armando</au><au>Martínez-Corona, Mónica B.</au><au>López-López, Marisol</au><au>Toscano-Garibay, Julia D.</au><au>Cuevas-Schacht, Francisco</au><au>Coria-Jiménez, Victor R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis</atitle><jtitle>Current microbiology</jtitle><stitle>Curr Microbiol</stitle><date>2022-11-01</date><risdate>2022</risdate><volume>79</volume><issue>11</issue><spage>353</spage><epage>353</epage><pages>353-353</pages><artnum>353</artnum><issn>0343-8651</issn><eissn>1432-0991</eissn><abstract>Pseudomonas aeruginosa has a high adaptive capacity, favoring the selection of antibiotic-resistant strains, which are currently considered a global health problem. The purpose of this work was to investigate the rate and distribution of extensively drug-resistant (XDR) P. aeruginosa in pediatric patients with cystic fibrosis (CF) with recurrent infections and to distinguish the current efficacy of antibiotics commonly used in eradication therapy at a Mexican institute focused on children. A total of 118 P. aeruginosa isolates from 25 children with CF (2015–2019) underwent molecular identification, antimicrobial sensitivity tests, and Random Amplified Polymorphic DNA genotyping (RAPD-PCR). The bacterial isolates were grouped in 84 RAPD profiles, revealing a cross-infection between two sisters, whose resistance profile remained unchanged for more than 2 years. Furthermore, 77.1% (91/118) and 51.7% (61/118) of isolates showed in vitro susceptibility to ceftazidime and amikacin, respectively, antibiotics often used in eradication therapy at our institution. As well, 42.4% (50/118) were categorized as multi-drug resistant (MDR) and 12.7% (15/118) were XDR. Of these resistant isolates, 84.6% (55/65) were identified from patients with recurrent infections. The high frequency of XDR strains in children with CF should be considered a caution mark, as such resistance patterns are more commonly found in adult patients. Additionally, amikacin may soon prove ineffective. Careful use of available antibiotics is crucial before therapeutic possibilities are reduced and “antibiotic resistance crisis” worsens.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s00284-022-03048-4</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3975-7305</orcidid></addata></record>
fulltext fulltext
identifier ISSN: 0343-8651
ispartof Current microbiology, 2022-11, Vol.79 (11), p.353-353, Article 353
issn 0343-8651
1432-0991
language eng
recordid cdi_proquest_miscellaneous_2723160314
source SpringerLink Journals - AutoHoldings
subjects Amikacin
Antibiotic resistance
Antibiotics
Antiinfectives and antibacterials
Biomedical and Life Sciences
Biotechnology
Ceftazidime
Children
Cross-infection
Cystic fibrosis
Drug resistance
Eradication
Genotyping
Global health
Life Sciences
Microbiology
Multidrug resistance
Patients
Pediatrics
Polymerase chain reaction
Pseudomonas aeruginosa
Public health
Random amplified polymorphic DNA
Strains (organisms)
title High Rates of Extensively Drug-Resistant Pseudomonas aeruginosa in Children with Cystic Fibrosis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T18%3A04%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20Rates%20of%20Extensively%20Drug-Resistant%20Pseudomonas%20aeruginosa%20in%20Children%20with%20Cystic%20Fibrosis&rft.jtitle=Current%20microbiology&rft.au=Guti%C3%A9rrez-Santana,%20Juan%20C.&rft.date=2022-11-01&rft.volume=79&rft.issue=11&rft.spage=353&rft.epage=353&rft.pages=353-353&rft.artnum=353&rft.issn=0343-8651&rft.eissn=1432-0991&rft_id=info:doi/10.1007/s00284-022-03048-4&rft_dat=%3Cproquest_cross%3E2723160314%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2722747299&rft_id=info:pmid/&rfr_iscdi=true