Emergence of Multidrug-Resistant Influenza A(H1N1)pdm09 Virus Variants in an Immunocompromised Child Treated With Oseltamivir and Zanamivir

Daisuke Tamura; Roberta L DeBiasi; Margaret Okomo-Adhiambo; Vasiliy P Mishin; Angela P Campbell; Brett Loechelt; Bernhard L Wiedermann; Alicia M Fry; Larisa V Gubareva

doi:10.1093/infdis/jiv245

Emergence of Multidrug-Resistant Influenza A(H1N1)pdm09 Virus Variants in an Immunocompromised Child Treated With Oseltamivir and Zanamivir

J Infect Dis. 2015 Oct 15;212(8):1209-13. doi: 10.1093/infdis/jiv245. Epub 2015 May 5.

Authors

Daisuke Tamura¹, Roberta L DeBiasi², Margaret Okomo-Adhiambo¹, Vasiliy P Mishin¹, Angela P Campbell¹, Brett Loechelt³, Bernhard L Wiedermann⁴, Alicia M Fry¹, Larisa V Gubareva¹

Affiliations

¹ Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
² Divisions of Pediatric Infectious Diseases Departments of Pediatrics Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine, Washington D.C.
³ Blood and Marrow Transplantation, Children's National Medical Center Departments of Pediatrics.
⁴ Divisions of Pediatric Infectious Diseases Departments of Pediatrics.

PMID: 25943200
DOI: 10.1093/infdis/jiv245

Abstract

Prolonged treatment of an immunocompromised child with oseltamivir and zanamivir for A(H1N1)pdm09 virus infection led to the emergence of viruses carrying H275Y and/or E119G in the neuraminidase (NA). When phenotypically evaluated by NA inhibition, the dual H275Y-E119G substitution caused highly reduced inhibition by 4 NA inhibitors: oseltamivir, zanamivir, peramivir, and laninamivir.

Keywords: drug resistance; neuraminidase; oseltamivir; pyrosequencing; zanamivir.

Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Acids, Carbocyclic
Amino Acid Substitution
Antiviral Agents / therapeutic use*
Cyclopentanes / therapeutic use
Drug Resistance, Viral / genetics*
Enzyme Inhibitors / therapeutic use*
Guanidines / therapeutic use
Humans
Immunocompromised Host
Infant
Influenza A Virus, H1N1 Subtype / drug effects
Influenza A Virus, H1N1 Subtype / genetics*
Influenza, Human / drug therapy
Influenza, Human / virology*
Male
Mutation, Missense
Neuraminidase / genetics*
Oseltamivir / therapeutic use
Pyrans
Sialic Acids
Viral Proteins / genetics
Zanamivir / analogs & derivatives
Zanamivir / therapeutic use

Substances

Acids, Carbocyclic
Antiviral Agents
Cyclopentanes
Enzyme Inhibitors
Guanidines
Pyrans
Sialic Acids
Viral Proteins
Oseltamivir
laninamivir
Neuraminidase
Zanamivir
peramivir