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2005 - 2006年流感季节初期在美国分离出的甲型流感病毒中的金刚烷胺耐药性。

Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States.

作者信息

Bright Rick A, Shay David K, Shu Bo, Cox Nancy J, Klimov Alexander I

机构信息

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Influenza Branch, Atlanta, Ga, USA.

出版信息

JAMA. 2006 Feb 22;295(8):891-4. doi: 10.1001/jama.295.8.joc60020. Epub 2006 Feb 2.

Abstract

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.

摘要

背景

金刚烷类药物,如金刚烷胺和金刚乙胺,多年来一直被用作抗甲型流感病毒社区暴发的首选抗病毒药物。全球范围内,对这些药物耐药的病毒比例一直在上升。对耐药病毒的出现和传播进行快速监测对于患者的恰当治疗至关重要。

目的

调查2005 - 2006年流感季节最初几个月在美国流行的对金刚烷类耐药的甲型流感病毒的频率。

设计与环境

作为正在进行的监测的一部分,对2005年10月1日至12月31日从26个州收集并提交给美国疾病控制与预防中心的流感病毒分离株进行耐药性检测。分离株来自世界卫生组织合作实验室和国家呼吸道及肠道病毒监测系统实验室。

主要观察指标

使用焦磷酸测序和确证试验,我们鉴定出M2基因内含有已知赋予对金刚烷胺和金刚乙胺耐药性的突变的病毒。

结果

对从26个州的患者中分离出的209株甲型流感病毒(H3N2)进行了筛查,其中193株(92.3%)在M2基因的第31位氨基酸(丝氨酸变为天冬酰胺[S31N])处发生了变化,已知该变化与金刚烷类耐药相关。8株甲型流感病毒(H1N1)中有2株含有相同突变。耐药病毒分布于美国各地。

结论

目前在美国流行的显示对金刚烷类耐药的甲型流感病毒比例很高,这突出了对抗病毒耐药性进行快速监测的临床重要性。我们的结果表明,在流行的甲型流感病毒分离株对金刚烷类重新恢复敏感性之前,这些药物不应在美国用于流感的治疗或预防。

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