Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States
Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States
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DOI：
10.1001/jama.295.8.joc60020
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发表时间：
2006-02-22
影响因子：
120.7
通讯作者：
Klimov, AI
中科院分区：
文献类型：
--
作者：
Bright, RA;Shay, DK;Klimov, AI
金刚烷类，金刚烷胺和金刚乙胺，多年来一直被用作社区甲型流感病毒爆发的首选抗病毒药物。在全球范围内，对这些药物具有耐药性的病毒比率一直在上升。快速监测耐药病毒的出现和传播已成为适当治疗患者的关键。目的调查2005-2006年流感季节前几个月美国出现的金刚烷耐药甲型流感病毒的频率。设计和背景2005年10月1日至12月31日期间从26个州收集并提交给美国疾病控制和预防中心的流感分离株进行了耐药性测试，作为持续监测的一部分。分离株来自世界卫生组织合作实验室和国家呼吸道和肠道病毒监测系统实验室。通过焦磷酸测序和验证性测定，我们鉴定出含有M2基因突变的病毒，已知这些病毒对金刚烷胺和金刚乙胺具有抗性。结果从26个州分离的甲型流感（H3N2）病毒209株中，有193株（92.3%）含有已知与金刚烷耐药相关的M2基因中第31个氨基酸（丝氨酸→天冬酰胺[S31N]）的变化。8种甲型H1N1流感病毒中有2种含有相同的突变。耐药病毒分布在美国各地。结论目前在美国流行的高比例甲型流感病毒显示金刚烷耐药，这突出了快速监测抗病毒药物耐药的临床重要性。我们的结果表明，在美国，这些药物不应用于治疗或预防流感，直到在流行的甲型流感分离株中重新建立金刚烷类药物的敏感性。
Context The adamantanes, amantadine and rimantadine, have been used as first-choice antiviral drugs against community outbreaks of influenza A viruses for many years. Rates of viruses resistant to these drugs have been increasing globally. Rapid surveillance for the emergence and spread of resistant viruses has become critical for appropriate treatment of patients.Objective To investigate the frequency of adamantane-resistant influenza A viruses circulating in the United States during the initial months of the 2005-2006 influenza season.Design and Setting Influenza isolates collected from 26 states from October 1 through December 31, 2005, and submitted to the US Centers for Disease Control and Prevention were tested for drug resistance as part of ongoing surveillance. Isolates were submitted from World Health Organization collaborating laboratories and National Respiratory and Enteric Virus Surveillance System laboratories.Main Outcome Measures Using pyrosequencing and confirmatory assays, we identified viruses containing mutations within the M2 gene that are known to confer resistance to both amantadine and rimantadine.Results A total of 209 influenza A(H3N2) viruses isolated from patients in 26 states were screened, of which 193 (92.3%) contained a change at amino acid 31 (serine to asparagine [S31N]) in the M2 gene known to be correlated with adamantane resistance. Two of 8 influenza A(H1N1) viruses contained the same mutation. Drug-resistant viruses were distributed across the United States.Conclusions The high proportion of influenza A viruses currently circulating in the United States demonstrating adamantane resistance highlights the clinical importance of rapid surveillance for antiviral resistance. Our results indicate that these drugs should not be used for the treatment or prophylaxis of influenza in the United States until susceptibility to adamantanes has been reestablished among circulating influenza A isolates.