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Prospective surveillance of antiviral resistance in hospitalized infants less than 12 months of age with A(H3N2) influenza infection and treated with oseltamivir

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  • Prospective surveillance of antiviral resistance in hospitalized infants less than 12 months of age with A(H3N2) influenza infection and treated with oseltamivir

    Antivir Ther. 2017 Feb 16. doi: 10.3851/IMP3141. [Epub ahead of print]
    Prospective surveillance of antiviral resistance in hospitalized infants less than 12 months of age with A(H3N2) influenza infection and treated with oseltamivir.

    Rath B1,2, Chen X1, Spies V3, Muehlhans S1, Obermeier P1, Tief F1, Seeber L1, Karsch K1, Milde J4, Skopnik H3, Schweiger B4, Duwe SC4.
    Author information

    Abstract

    BACKGROUND:

    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.
    METHODS:

    We performed a prospective surveillance of hospitalized infants undergoing oseltamivir therapy during the 2008-2009 and 2011-2012 influenza seasons at two paediatric hospitals in Germany. A total of 37 infants less than one year of age with laboratory confirmed influenza A(H3N2) infection received oseltamivir as per physician's order for 5 days (2008-2009 season: 2mg/kg BID; 2011-2012 season: 2.0 mg/kg; 2.5 mg/kg and 3.0 mg/kg BID for infants <1 month; 2-3 months and 4-12 months, respectively). Virus load, the susceptibility to neuraminidase inhibitors, and the presence of molecular markers of resistance to NAI was assessed for influenza viruses recovered from respiratory samples collected at baseline and during follow-up visits.
    RESULTS:

    Overall, 73% of the infants continued to shed viral RNA detectable by RT-PCR after dose #10 of oseltamivir (i.e. on day five); twelve infants shed viruses, two of them (both 9 months of age) shed resistant viruses. Resistance was characterized by ≥1000-fold increase of IC50 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 #10 on day 6).
    CONCLUSIONS:

    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.


    PMID: 28205506 DOI: 10.3851/IMP3141
    [PubMed - as supplied by publisher]
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