{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:00:34Z","timestamp":1790913634076,"version":"4.1.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Infants exhibit elevated influenza virus loads and prolonged viral shedding, which may increase the risk for resistance development, especially in cases of suboptimal exposure to antiviral therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a prospective surveillance of hospitalized infants undergoing oseltamivir therapy during the 2008\u20132009 and 2011\u20132012 influenza seasons at two paediatric hospitals in Germany. A total of 37 infants less than 1 year of age with laboratory confirmed influenza A(H3N2) infection received oseltamivir as per physician's order for 5 days (2008\u20132009 season: 2 mg\/kg twice daily; 2011\u20132012 season: 2.0 mg\/kg; 2.5 mg\/kg and 3.0 mg\/kg twice daily for infants &lt;1 month; 2\u20133 months and 4\u201312 months, respectively). Virus load, the susceptibility to neuraminidase inhibitors (NAIs), and the presence of molecular markers of resistance to NAIs was assessed for influenza viruses recovered from respiratory samples collected at baseline and during follow-up visits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 73% of the infants continued to shed viral RNA detectable by reverse transcription (RT)-PCR after dose number 10 of oseltamivir; 12 infants shed viruses, 2 of them (both 9 months of age) shed resistant viruses. Resistance was characterized by \u22651,000-fold increase of 50% inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) for oseltamivir, up to 50-fold for zanamivir and elevated Km values when compared to susceptible A(H3N2) strains. Sanger sequencing revealed the selection of the NA-R292K substitution in both instances (after dose number 10 on day 6).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that it may be relevant to monitor antiviral resistance systematically in all infants, considering that the European Medicines Agency has recently extended the licensure for oseltamivir to include full-term infants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3141","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T06:49:03Z","timestamp":1487227743000},"page":"515-522","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Prospective Surveillance of Antiviral Resistance in Hospitalized Infants Less than 12 Months of Age with A(H3N2) Influenza Infection and Treated with Oseltamivir"],"prefix":"10.1177","volume":"22","author":[{"given":"Barbara","family":"Rath","sequence":"first","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"},{"name":"Vienna Vaccine Safety Initiative, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Spies","sequence":"additional","affiliation":[{"name":"Klinikum Worms, Department of Pediatrics and Adolescent Medicine, Worms, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"Muehlhans","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Obermeier","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Tief","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Seeber","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Karsch","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medical Center, Department of Pediatrics, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Milde","sequence":"additional","affiliation":[{"name":"Robert Koch Institute, Division of Influenza Viruses and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heino","family":"Skopnik","sequence":"additional","affiliation":[{"name":"Klinikum Worms, Department of Pediatrics and Adolescent Medicine, Worms, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunhilde","family":"Schweiger","sequence":"additional","affiliation":[{"name":"Robert Koch Institute, Division of Influenza Viruses and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne C","family":"Duwe","sequence":"additional","affiliation":[{"name":"Robert Koch Institute, Division of Influenza Viruses and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,8,1]]},"reference":[{"key":"bibr1-IMP3141","unstructured":"WHO. Influenza (seasonal). Fact sheet N\u00b0211, March 2014. (Accessed 25 November 2015.) Available from http:\/\/www.who.int\/mediacentre\/factsheets\/fs211\/en\/."},{"key":"bibr2-IMP3141","unstructured":"Europe WHO. Influenza H1N1 (2009) key issues for case management 2011 (Accessed 25 November 2015.) Available from http:\/\/www.euro.who.int\/__data\/assets\/pdf_file\/0008\/130859\/H1N1_key_issues_case_mgt_update.pdf?ua=1."},{"key":"bibr3-IMP3141","unstructured":"EMA. Tamiflu-oseltamivir 2015. EMA\/266618\/2015. (Accessed 25 November 2015.) Available from http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Summary_for_the_public\/human\/000402\/WC500033101.pdf."},{"key":"bibr4-IMP3141","unstructured":"FDA. Tamiflu (oseltamivir phosphate) information. (Accessed 25 July 2017.) 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WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza and other influenza viruses, 2010. (Accessed 25 November 2015.) Available from http:\/\/www.who.int\/csr\/resources\/publications\/swineflu\/h1n1_use_antivirals_20090820\/en\/index.html."},{"key":"bibr28-IMP3141","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009966"},{"key":"bibr29-IMP3141","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092500"},{"key":"bibr30-IMP3141","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.15.8418-8425.2003"},{"key":"bibr31-IMP3141","unstructured":"WHO. Global, Influenza, Surveillance, Network. Manual for the laboratory diagnosis and virological surveillance of influenza Switzerland; 2011. (Accessed 25 November 2015.) 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