title: In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against clinical isolates of the influenza virus circulating in the Japanese 2013-2014 season.
abstract: To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC50) of neuraminidase inhibitors (NAIs) for the influenza virus isolates in the 2013-2014 influenza season and compared the results to those of the 2010-2011 to 2012-2013 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 327 influenza viruses were isolated: 172 influenza A(H1N1)pdm09 (52.6%), 49 A(H3N2) (15.0%), and 106 B (32.4%). Numbers of Victoria and Yamagata lineage isolates were 36 and 70, respectively. Two A(H1N1)pdm09 isolates showed a high IC50 for oseltamivir (130 and 150 nM) exceeding by 100 times the geometric mean of the IC50 of oseltamivir for A(H1N1)pdm09 isolates (0.76 nM). No isolate showed a very high IC50 for A(H3N2) or B. The IC50 of the NAIs except for oseltamivir for A(H1N1) pdm09 were significantly higher than those of the 2010-2011 season (P < 0.05). The IC50 of all four NAIs for A(H3N2) were significantly lower than those of the 2012-2013 season (P < 0.001). The IC50 of the NAIs for B except for oseltamivir were significantly lower than those of the 2012-2013 season (P < 0.001). Although there are some isolates that show highly reduced sensitivity to oseltamivir among A(H1N1)pdm09 isolates, the currently epidemic influenza A(H1N1)pdm09, A(H3N2) and B viruses are susceptible to all four NAIs with no trend toward decreased sensitivity.
authors.affiliation: Japan Physicians Association, Tokyo, Japan. Electronic address: ikematsu@gray.plala.or.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawai
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Iwaki
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Seizabro
authors.initials: S
authors.lastname: Kashiwagi
mesh_terms: D000146:Acids, Carbocyclic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003517:Cyclopentanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000201:enzymology; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology; D007251:Influenza, Human / Q000821:virology*; D020128:Inhibitory Concentration 50; D007564:Japan; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000494:pharmacology*; D011714:Pyrans; D012794:Sialic Acids; D013997:Time Factors; D055815:Young Adult; D053243:Zanamivir / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000146:Acids, Carbocyclic; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; C546918:laninamivir; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir
keywords: 50% Inhibitory concentration; Influenza; Laninamivir; Oseltamivir; Peramivir; Zanamivir