Frequency of drug-resistant viruses and virus shedding in pediatric influenza patients treated with neuraminidase inhibitors.
BACKGROUND
Although influenza virus resistance to the neuraminidase inhibitor zanamivir is reported less frequently than is resistance to the neuraminidase inhibitor oseltamivir in clinical settings, it is unknown whether this difference is due to the limited use of zanamivir or to an inherent property of the drug. We therefore compared the prevalence of drug-resistant viruses and virus shedding in seasonal influenza virus-infected children treated with either oseltamivir or zanamivir.


METHODS
Clinical specimens (throat or nasal swab) were collected from a total of 144 pediatric influenza patients during the 2005-2006, 2006-2007, 2007-2008, and 2008-2009 influenza seasons. Neuraminidase inhibitor-resistant mutants were detected among the isolated viruses by sequencing the viral hemagglutinin and neuraminidase genes. Sensitivity of the viruses to neuraminidase inhibitors was tested by neuraminidase inhibition assay.


RESULTS
In oseltamivir- or zanamivir-treated influenza patients who were statistically comparable in their age distribution, vaccination history, and type or subtype of virus isolates, the virus-shedding period in zanamivir-treated patients was significantly shorter than that in oseltamivir-treated patients. Furthermore, the frequency of zanamivir-resistant viruses was significantly lower than that of oseltamivir-resistant viruses.


CONCLUSIONS
In comparison with treatment with oseltamivir, treatment of pediatric patients with zanamivir resulted in the emergence of fewer drug-resistant influenza viruses and a shorter virus-shedding period. We conclude that zanamivir shows promise as a better therapy for pediatric influenza patients.
Division of Virology, Department of Microbiology and Immunology, Institute of MedicalScience, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
Daisuke
D
Tamura
Norio
N
Sugaya
Makoto
M
Ozawa
Ryo
R
Takano
Masataka
M
Ichikawa
Masahiko
M
Yamazaki
Chiharu
C
Kawakami
Hideaki
H
Shimizu
Ritei
R
Uehara
Maki
M
Kiso
Eiryo
E
Kawakami
Keiko
K
Mitamura
Yoshihiro
Y
Kawaoka
D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008826:Microbial Sensitivity Tests; D009297:Nasal Mucosa / Q000821:virology; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000302:isolation & purification; D053139:Oseltamivir / Q000494:pharmacology / Q000627:therapeutic use*; D010614:Pharynx / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D017201:Virus Shedding; D053243:Zanamivir / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D012367:RNA, Viral; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir
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