Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage
Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; i...
Gespeichert in:
Veröffentlicht in: | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2020-07, Vol.26 (7), p.745-748 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 748 |
---|---|
container_issue | 7 |
container_start_page | 745 |
container_title | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy |
container_volume | 26 |
creator | Yamada, Nami Nakamoto, Takato Takei, Haruka Shoji, Takayo Takahashi, Kaori Sato, Junichi Takeuchi, Noriko Ohkusu, Misako Ishiwada, Naruhiko |
description | Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future. |
doi_str_mv | 10.1016/j.jiac.2020.02.013 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2377679849</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1341321X20300611</els_id><sourcerecordid>2377679849</sourcerecordid><originalsourceid>FETCH-LOGICAL-c446t-30d94f0835d03c28d92413ded57796c5ea2dd58073b573c897ea5be7b53cd91e3</originalsourceid><addsrcrecordid>eNp9kE1v1DAQhq2qqC2FP8Ch8rGHJvgjjp2KS1vxJVXi0EXiZjn2bPEqsYPtgHrir-PVFo6cZjR63leaB6E3lLSU0P7trt15Y1tGGGkJawnlR-iMdlw2UipyXHfe0YYz-u0Uvcx5RwiVQqkTdFpvkvZCnaHfm18RW5Mh47jFo7EFkjcTniH48OiLz9itgEuslxQXCDA3CbLPxYSCH0qCpUQbrV0zXgKscwzewDW-weV7AlP2rbkmy9MCmIvbK_ywwUIoPPkA5hFeoRdbM2V4_TzP0dcP7zd3n5r7Lx8_393cN7br-tJw4oZuSxQXjnDLlBtYR7kDJ6QceivAMOeEIpKPQnKrBglGjCBHwa0bKPBzdHnoXVL8sUIuevbZwjSZAHHNmnEpezmobqgoO6A2xZwTbPWS_GzSk6ZE78Xrnd6L13vxmjBdxdfQxXP_Os7g_kX-mq7AuwMA9cufHpLO1kOw4HwCW7SL_n_9fwAFR5Sj</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2377679849</pqid></control><display><type>article</type><title>Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Yamada, Nami ; Nakamoto, Takato ; Takei, Haruka ; Shoji, Takayo ; Takahashi, Kaori ; Sato, Junichi ; Takeuchi, Noriko ; Ohkusu, Misako ; Ishiwada, Naruhiko</creator><creatorcontrib>Yamada, Nami ; Nakamoto, Takato ; Takei, Haruka ; Shoji, Takayo ; Takahashi, Kaori ; Sato, Junichi ; Takeuchi, Noriko ; Ohkusu, Misako ; Ishiwada, Naruhiko</creatorcontrib><description>Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.</description><identifier>ISSN: 1341-321X</identifier><identifier>EISSN: 1437-7780</identifier><identifier>DOI: 10.1016/j.jiac.2020.02.013</identifier><identifier>PMID: 32171658</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Bacterial meningitis ; beta-Alanine - analogs & derivatives ; beta-Alanine - pharmacology ; beta-Alanine - therapeutic use ; Cefotaxime - pharmacology ; Cefotaxime - therapeutic use ; Drug Resistance, Multiple, Bacterial - genetics ; Female ; Humans ; Infant ; Male ; Meningitis, Pneumococcal - blood ; Meningitis, Pneumococcal - diagnosis ; Meningitis, Pneumococcal - drug therapy ; Meningitis, Pneumococcal - microbiology ; Meropenem - pharmacology ; Meropenem - therapeutic use ; Meropenem-resistant Streptococcus pneumoniae ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Pneumococcal Vaccines - administration & dosage ; Serotype 35B ; Serotyping ; Streptococcus pneumoniae - drug effects ; Streptococcus pneumoniae - genetics ; Streptococcus pneumoniae - isolation & purification ; Thienamycins - pharmacology ; Thienamycins - therapeutic use ; Treatment Outcome</subject><ispartof>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2020-07, Vol.26 (7), p.745-748</ispartof><rights>2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases</rights><rights>Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-30d94f0835d03c28d92413ded57796c5ea2dd58073b573c897ea5be7b53cd91e3</citedby><cites>FETCH-LOGICAL-c446t-30d94f0835d03c28d92413ded57796c5ea2dd58073b573c897ea5be7b53cd91e3</cites><orcidid>0000-0002-0547-1026 ; 0000-0002-7508-1330</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32171658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Nami</creatorcontrib><creatorcontrib>Nakamoto, Takato</creatorcontrib><creatorcontrib>Takei, Haruka</creatorcontrib><creatorcontrib>Shoji, Takayo</creatorcontrib><creatorcontrib>Takahashi, Kaori</creatorcontrib><creatorcontrib>Sato, Junichi</creatorcontrib><creatorcontrib>Takeuchi, Noriko</creatorcontrib><creatorcontrib>Ohkusu, Misako</creatorcontrib><creatorcontrib>Ishiwada, Naruhiko</creatorcontrib><title>Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage</title><title>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</title><addtitle>J Infect Chemother</addtitle><description>Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Bacterial meningitis</subject><subject>beta-Alanine - analogs & derivatives</subject><subject>beta-Alanine - pharmacology</subject><subject>beta-Alanine - therapeutic use</subject><subject>Cefotaxime - pharmacology</subject><subject>Cefotaxime - therapeutic use</subject><subject>Drug Resistance, Multiple, Bacterial - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Meningitis, Pneumococcal - blood</subject><subject>Meningitis, Pneumococcal - diagnosis</subject><subject>Meningitis, Pneumococcal - drug therapy</subject><subject>Meningitis, Pneumococcal - microbiology</subject><subject>Meropenem - pharmacology</subject><subject>Meropenem - therapeutic use</subject><subject>Meropenem-resistant Streptococcus pneumoniae</subject><subject>Microbial Sensitivity Tests</subject><subject>Multilocus Sequence Typing</subject><subject>Pneumococcal Vaccines - administration & dosage</subject><subject>Serotype 35B</subject><subject>Serotyping</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Streptococcus pneumoniae - genetics</subject><subject>Streptococcus pneumoniae - isolation & purification</subject><subject>Thienamycins - pharmacology</subject><subject>Thienamycins - therapeutic use</subject><subject>Treatment Outcome</subject><issn>1341-321X</issn><issn>1437-7780</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhq2qqC2FP8Ch8rGHJvgjjp2KS1vxJVXi0EXiZjn2bPEqsYPtgHrir-PVFo6cZjR63leaB6E3lLSU0P7trt15Y1tGGGkJawnlR-iMdlw2UipyXHfe0YYz-u0Uvcx5RwiVQqkTdFpvkvZCnaHfm18RW5Mh47jFo7EFkjcTniH48OiLz9itgEuslxQXCDA3CbLPxYSCH0qCpUQbrV0zXgKscwzewDW-weV7AlP2rbkmy9MCmIvbK_ywwUIoPPkA5hFeoRdbM2V4_TzP0dcP7zd3n5r7Lx8_393cN7br-tJw4oZuSxQXjnDLlBtYR7kDJ6QceivAMOeEIpKPQnKrBglGjCBHwa0bKPBzdHnoXVL8sUIuevbZwjSZAHHNmnEpezmobqgoO6A2xZwTbPWS_GzSk6ZE78Xrnd6L13vxmjBdxdfQxXP_Os7g_kX-mq7AuwMA9cufHpLO1kOw4HwCW7SL_n_9fwAFR5Sj</recordid><startdate>202007</startdate><enddate>202007</enddate><creator>Yamada, Nami</creator><creator>Nakamoto, Takato</creator><creator>Takei, Haruka</creator><creator>Shoji, Takayo</creator><creator>Takahashi, Kaori</creator><creator>Sato, Junichi</creator><creator>Takeuchi, Noriko</creator><creator>Ohkusu, Misako</creator><creator>Ishiwada, Naruhiko</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0547-1026</orcidid><orcidid>https://orcid.org/0000-0002-7508-1330</orcidid></search><sort><creationdate>202007</creationdate><title>Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage</title><author>Yamada, Nami ; Nakamoto, Takato ; Takei, Haruka ; Shoji, Takayo ; Takahashi, Kaori ; Sato, Junichi ; Takeuchi, Noriko ; Ohkusu, Misako ; Ishiwada, Naruhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-30d94f0835d03c28d92413ded57796c5ea2dd58073b573c897ea5be7b53cd91e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Bacterial meningitis</topic><topic>beta-Alanine - analogs & derivatives</topic><topic>beta-Alanine - pharmacology</topic><topic>beta-Alanine - therapeutic use</topic><topic>Cefotaxime - pharmacology</topic><topic>Cefotaxime - therapeutic use</topic><topic>Drug Resistance, Multiple, Bacterial - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Meningitis, Pneumococcal - blood</topic><topic>Meningitis, Pneumococcal - diagnosis</topic><topic>Meningitis, Pneumococcal - drug therapy</topic><topic>Meningitis, Pneumococcal - microbiology</topic><topic>Meropenem - pharmacology</topic><topic>Meropenem - therapeutic use</topic><topic>Meropenem-resistant Streptococcus pneumoniae</topic><topic>Microbial Sensitivity Tests</topic><topic>Multilocus Sequence Typing</topic><topic>Pneumococcal Vaccines - administration & dosage</topic><topic>Serotype 35B</topic><topic>Serotyping</topic><topic>Streptococcus pneumoniae - drug effects</topic><topic>Streptococcus pneumoniae - genetics</topic><topic>Streptococcus pneumoniae - isolation & purification</topic><topic>Thienamycins - pharmacology</topic><topic>Thienamycins - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Nami</creatorcontrib><creatorcontrib>Nakamoto, Takato</creatorcontrib><creatorcontrib>Takei, Haruka</creatorcontrib><creatorcontrib>Shoji, Takayo</creatorcontrib><creatorcontrib>Takahashi, Kaori</creatorcontrib><creatorcontrib>Sato, Junichi</creatorcontrib><creatorcontrib>Takeuchi, Noriko</creatorcontrib><creatorcontrib>Ohkusu, Misako</creatorcontrib><creatorcontrib>Ishiwada, Naruhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Nami</au><au>Nakamoto, Takato</au><au>Takei, Haruka</au><au>Shoji, Takayo</au><au>Takahashi, Kaori</au><au>Sato, Junichi</au><au>Takeuchi, Noriko</au><au>Ohkusu, Misako</au><au>Ishiwada, Naruhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage</atitle><jtitle>Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy</jtitle><addtitle>J Infect Chemother</addtitle><date>2020-07</date><risdate>2020</risdate><volume>26</volume><issue>7</issue><spage>745</spage><epage>748</epage><pages>745-748</pages><issn>1341-321X</issn><eissn>1437-7780</eissn><abstract>Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>32171658</pmid><doi>10.1016/j.jiac.2020.02.013</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-0547-1026</orcidid><orcidid>https://orcid.org/0000-0002-7508-1330</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1341-321X |
ispartof | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2020-07, Vol.26 (7), p.745-748 |
issn | 1341-321X 1437-7780 |
language | eng |
recordid | cdi_proquest_miscellaneous_2377679849 |
source | MEDLINE; Alma/SFX Local Collection |
subjects | Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Bacterial meningitis beta-Alanine - analogs & derivatives beta-Alanine - pharmacology beta-Alanine - therapeutic use Cefotaxime - pharmacology Cefotaxime - therapeutic use Drug Resistance, Multiple, Bacterial - genetics Female Humans Infant Male Meningitis, Pneumococcal - blood Meningitis, Pneumococcal - diagnosis Meningitis, Pneumococcal - drug therapy Meningitis, Pneumococcal - microbiology Meropenem - pharmacology Meropenem - therapeutic use Meropenem-resistant Streptococcus pneumoniae Microbial Sensitivity Tests Multilocus Sequence Typing Pneumococcal Vaccines - administration & dosage Serotype 35B Serotyping Streptococcus pneumoniae - drug effects Streptococcus pneumoniae - genetics Streptococcus pneumoniae - isolation & purification Thienamycins - pharmacology Thienamycins - therapeutic use Treatment Outcome |
title | Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T01%3A09%3A10IST&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=Two%20cases%20of%20bacterial%20meningitis%20due%20to%20meropenem-resistant%20Streptococcus%20pneumoniae:%20A%20threat%20of%20serotype%2035B,%20ST%20558%20lineage&rft.jtitle=Journal%20of%20infection%20and%20chemotherapy%20:%20official%20journal%20of%20the%20Japan%20Society%20of%20Chemotherapy&rft.au=Yamada,%20Nami&rft.date=2020-07&rft.volume=26&rft.issue=7&rft.spage=745&rft.epage=748&rft.pages=745-748&rft.issn=1341-321X&rft.eissn=1437-7780&rft_id=info:doi/10.1016/j.jiac.2020.02.013&rft_dat=%3Cproquest_cross%3E2377679849%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=2377679849&rft_id=info:pmid/32171658&rft_els_id=S1341321X20300611&rfr_iscdi=true |