Primarily Oseltamivir-Resistant Influenza a (H1N1pdm09) virus Evolving into a Multidrug-Resistant virus Carrying H275Y and I223R Neuraminidase Substitutions
Free accessCase reportFirst published online January, 2015
Primarily Oseltamivir-Resistant Influenza a (H1N1pdm09) virus Evolving into a Multidrug-Resistant virus Carrying H275Y and I223R Neuraminidase Substitutions
Antiviral susceptibility testing and reporting of viruses carrying amino acid substitutions conferring antiviral drug resistance is essential to assess the spread and clinical impact of these viruses. Here, we report on a patient who was infected with a primarily oseltamivir-resistant influenza A (H1N1pdm09) virus following allogeneic stem cell transplantation and rituximab treatment. Under prolonged virus replication and zanamivir therapy the neuraminidase amino acid substitutions H275Y and I223R were detected conferring high-level resistance to oseltamivir and cross-resistance to zanamivir. The emergence of these amino acid changes has been reported rarely worldwide and has been associated with fatal clinical outcomes. The patient survived the influenza infection after 170 days of follow-up.
References
1.
ThorlundK., AwadT., BoivinG.Systematic review of influenza resistance to the neuraminidase inhibitors.BMC Infect Dis2011; 11: 134.
2.
NguyenH.T., TrujilloA.A., SheuT.G.Analysis of influenza viruses from patients clinically suspected of infection with an oseltamivir resistant virus during the 2009 pandemic in the United States.Antiviral Res2012; 93: 381–386.
3.
GraitcerS.B., GubarevaL., KamimotoL.Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009, United States.Emerg Infect Dis2011; 17: 255–257.
4.
MehtaT., McGrathE., BheemreddyS.Detection of oseltamivir resistance during treatment of 2009 H1N1 influenza virus infection in immunocompromised patients: utility of cycle threshold values of qualitative real-time reverse transcriptase PCR.J Clin Microbiol2010; 48: 4326–4328.
5.
LeGoffJ., RoussetD., Abou-JaoudeG.I223R mutation in influenza A(H1N1)pdm09 neuraminidase confers reduced susceptibility to oseltamivir and zanamivir and enhanced resistance with H275Y.PLoS ONE2012; 7: e37095.
6.
NguyenH.T., FryA.M., LovelessP.A.Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir.Clin Infect Dis2010; 51: 983–984.
7.
van der VriesE., StelmaF.F., BoucherC.A.Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus.N Engl J Med2010; 363: 1381–1382.
8.
PizzornoA., AbedY., BouhyX.Impact of mutations at residue I223 of the neuraminidase protein on the resistance profile, replication level, and virulence of the 2009 pandemic influenza virus.Antimicrob Agents Chemother2012; 56: 1208–1214.
9.
DeydeV.M., SheuT.G., TrujilloA.A.Detection of molecular markers of drug resistance in 2009 pandemic influenza A (H1N1) viruses by pyrosequencing.Antimicrob Agents Chemother2010; 54: 1102–1110.
10.
BrookesD.W., MiahS., LackenbyA.Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitness.J Antimicrob Chemother2011; 66: 466–470.
11.
TramontanaA.R., GeorgeB., HurtA.C.Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia.Emerg Infect Dis2010; 16: 1068–1075.
12.
HungI.F., ToK.K., LeeC.K.Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.Clin Infect Dis2011; 52: 447–456.
