National Reference Laboratory for Antimicrobial Resistance, Research and Development Unit, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, Lisbon, Portugal.
Antiviral Res. 2010 May;86(2):128-36. doi: 10.1016/j.antiviral.2010.01.002. Epub 2010 Jan 18.
A research project on antiviral drug resistance of influenza viruses circulating in Portugal has been carried out since 2007. Here, the first results obtained regarding the evaluation of susceptibility to amantadine and oseltamivir are presented. Information about antiviral prescription and exposure was available through the National Influenza Surveillance Programme. Amantadine susceptibility was evaluated by pyrosequencing for known resistance markers on 178 influenza A strains from 2004/2005 to 2006/2007. Susceptibility to oseltamivir was evaluated by 50% inhibitory concentration determination on 340 virus strains from 2004/2005 to 2008/2009, 134 of which were further analyzed by sequencing of the neuraminidase gene. This study revealed that influenza antiviral drugs were rarely prescribed at national level. Resistance to amantadine was observed on only A(H3N2) strain isolated during 2005/2006 and on 38 (74.5%) of the 51 A(H3N2) strains from 2006/2007, all carrying the mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 6 (20.7%) of the 29 A(H1N1) strains from 2007/2008 and in all strains from 2008/2009, which exhibited extremely high IC(50) values and carrying the mutation H275Y in their neuraminidase sequence. The national data generated and analyzed in this study may contribute to increase the knowledge on influenza antiviral drug resistance which is a problem of global concern.
自 2007 年以来，一直在开展一项针对葡萄牙流行的流感病毒的抗病毒药物耐药性研究项目。在此，介绍了关于评估金刚烷胺和奥司他韦敏感性的首批结果。通过国家流感监测计划获得了有关抗病毒药物处方和暴露的信息。通过焦磷酸测序评估了 2004/2005 年至 2006/2007 年的 178 株流感 A 株的已知耐药标记物对金刚烷胺的敏感性。通过测定 340 株病毒株（2004/2005 年至 2008/2009 年）的 50%抑制浓度来评估奥司他韦的敏感性，其中 134 株进一步通过神经氨酸酶基因测序进行了分析。这项研究表明，在全国范围内很少开流感抗病毒药物。仅在 2005/2006 年分离的 A(H3N2)株和 2006/2007 年的 51 株 A(H3N2)株中的 38 株（74.5%）观察到对金刚烷胺的耐药性，所有这些株均在其 M2 序列中携带 S31N 突变。在 2007/2008 年的 29 株 A(H1N1)株中的 6 株（20.7%）和 2008/2009 年的所有株中均观察到奥司他韦耐药性，这些株的 IC（50）值极高，并且在其神经氨酸酶序列中携带 H275Y 突变。本研究产生和分析的全国数据可能有助于增加对全球关注的流感抗病毒药物耐药性问题的了解。
