Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
Pediatr Infect Dis J. 2011 Apr;30(4):284-8. doi: 10.1097/INF.0b013e3181ff863b.
Immunocompromised patients are highly susceptible to influenza infection and can have prolonged viral shedding, which is a risk factor for the development of antiviral resistance.
We investigated the emergence of oseltamivir-resistant influenza variants in children and young adults with cancer during the 2002-2008 influenza seasons. The demographic and clinical features of influenza infections in 12 patients who had viral isolates obtained before and after oseltamivir therapy was initiated were studied. Antiviral susceptibilities were determined by the fluorescence-based neuraminidase (NA) enzyme inhibition assay and by sequencing genes encoding NA and matrix M2 proteins.
The mean age of patients was 10.5 (range, 1.1-23.0) years. Ten patients had hematologic malignancies, 4 were recipients of hematopoietic stem cell transplants, and all patients were receiving immunosuppressive therapy. Eleven patients had prolonged respiratory symptoms and 8 had prolonged viral shedding. Serial viral isolates were available for 8 of 12 patients. Oseltamivir-resistant influenza viruses were isolated from 4 children (3 influenza A [H3N2] and 1 influenza B virus): before the initiation of antiviral therapy in 2 patients and during therapy in the other 2 patients. Three resistant influenza A (H3N2) viruses shared a common E119V NA mutation. One patient was infected with oseltamivir-resistant influenza B virus (IC50, 731.86 ± 155.12 nM) that harbored a N294S NA mutation, the first report of this mutation in influenza B viruses.
Oseltamivir-resistant influenza viruses can exist before or rapidly emerge during antiviral therapy in immunocompromised individuals, and this has important implications for therapy and infection control.
免疫功能低下的患者极易感染流感，并且可能会出现病毒持续排出，这是产生抗病毒药物耐药性的一个危险因素。
我们研究了在 2002 年至 2008 年流感季节期间，癌症患儿和年轻成年患者中奥司他韦耐药流感变异株的出现情况。研究了 12 例患者在开始奥司他韦治疗前后获得病毒分离物的流感感染的人口统计学和临床特征。通过基于荧光的神经氨酸酶（NA）酶抑制测定法和测序编码 NA 和基质 M2 蛋白的基因来确定抗病毒药物敏感性。
患者的平均年龄为 10.5 岁（范围，1.1-23.0 岁）。10 例患者患有血液系统恶性肿瘤，4 例患者接受了造血干细胞移植，所有患者均接受免疫抑制治疗。11 例患者有持续的呼吸道症状，8 例患者有持续的病毒排出。12 例患者中有 8 例可获得连续的病毒分离物。4 例儿童（3 例甲型流感[H3N2]和 1 例乙型流感病毒）分离出奥司他韦耐药流感病毒：2 例患者在开始抗病毒治疗前，2 例患者在治疗期间。3 例耐药的甲型流感（H3N2）病毒共享一个常见的 E119V NA 突变。1 例患者感染了奥司他韦耐药的乙型流感病毒（IC50，731.86±155.12 nM），该病毒携带 N294S NA 突变，这是乙型流感病毒中首次报道该突变。
在免疫功能低下的个体中，奥司他韦耐药的流感病毒可能在抗病毒治疗前存在或在治疗期间迅速出现，这对治疗和感染控制具有重要意义。
