Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children
Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children
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DOI：
10.1086/596311
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发表时间：
2009-02-15
影响因子：
11.8
通讯作者：
Zambon, Maria
中科院分区：
文献类型：
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作者：
Stephenson, Iain;Democratis, Jane;Zambon, Maria
背景。奥司他韦是一种特异性流感神经氨酸酶抑制剂，是治疗季节性流感的有效药物。据报道，治疗后会出现耐药流感病毒，特别是在日本的儿童中，因为日本的给药方案与世界其他地区使用的方案不同。我们调查了接受基于体重的分级给药方案治疗的儿童中耐药感染的出现情况。方法。我们分析了 2005 年至 2007 年期间患有急性流感的儿童在奥司他韦分层治疗前后获得的连续临床鼻咽样本。我们分离了病毒，使用基于荧光的神经氨酸酶抑制测定法测试了耐药性，进行了神经氨酸酶基因测序，并确定了定量病毒载量。结果。纳入64名1-12岁（中位年龄3岁1个月）儿童（34名甲型H3N2流感、11名甲型H1N1流感、19名乙型流感病毒）。治疗开始后第 4-7 天，在 64 个测试样本中，通过逆转录聚合酶链式反应和培养分别检测到 47 个样本 (73.4%) 和 26 个样本 (40.6%) 检测到病毒。治疗开始后第 8-12 天，在 53 个测试样本中，通过逆转录酶聚合酶链反应和培养分别检测到 18 个（33.9%）和 1 个（1.8%）病毒。我们发现病毒亚型之间的病毒脱落减少或病毒清除时间没有统计学上的显着差异。从 11 名甲型 H1N1 流感儿童中的 3 名（27.3%）、34 名甲型 H3N2 流感儿童中的 1 名（2.9%）和 19 名乙型流感病毒儿童中的 0 名（0%）中回收到抗病毒耐药病毒，所有这些儿童都接受了奥司他韦治疗（P = .004）。没有证据表明感染耐药病毒的儿童会长期患病。结论。在基于体重的分级奥司他韦治疗后，甲型 H1N1 流感病毒的耐药性出现率高于甲型 H3N2 流感或乙型流感病毒。对耐药模式的病毒学监测对于确定抗病毒治疗策略和大流行防范储备的组成至关重要。
Background. Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen.Methods. We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005-2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads.Results. Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1-12 years (median age, 3 years, 1 month) were enrolled. By days 4-7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8-12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir (P = .004) There was no evidence of prolonged illness in children infected with drug-resistant virus.Conclusions. Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.