title: In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 Japanese influenza seasons.
abstract: To assess the extent of viral resistance to the four neuraminidase inhibitors (NAIs), we measured their 50% inhibitory concentration (IC50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 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. IC50 was measured for 200 influenza A(H3N2) and 19 influenza B in the 2014-2015 season, and no virus with highly reduced sensitivity to the four NAIs was detected. The ratios of the geometric means of the A(H3N2) IC50s of 2014-2015 to those of the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 seasons ranged from 0.72 to 1.05, 0.82 to 1.22, 0.69 to 1.00, and 0.70 to 1.03, respectively. The ratios of the geometric mean of the B IC50s to the previous four seasons ranged from 0.59 to 1.28, 0.66 to 1.34, 0.84 to 1.21, and 1.06 to 1.47, respectively. There was no trend in the change of the IC50s for A(H3N2) or B. Significant differences were found in some seasons, but the differences in the IC50s were all less than two fold. These results show change in the geometric mean IC50 by season but with no trend, which indicates that the influence of viral mutation on the effectiveness of these NAIs was minute for A(H3N2) and B over the past five seasons.
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: Seizaburo
authors.initials: S
authors.lastname: Kashiwagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification; D009981:Influenza B virus / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy*; D020128:Inhibitory Concentration 50; D007564:Japan; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011358:Product Surveillance, Postmarketing; D055815:Young Adult; D053243:Zanamivir / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009439:Neuraminidase; D053243:Zanamivir
keywords: A(H3N2); B; IC(50); Influenza; Neuraminidase inhibitor; Resistance