Longitudinal Characterization of Herpes Simplex Virus (HSV) Isolates Acquired From Different Sites in an Immune-Compromised Child: A New HSV Thymidine Kinase Mutation Associated With Resistance.
Longitudinal Characterization of Herpes Simplex Virus (HSV) Isolates Acquired From Different Sites in an Immune-Compromised Child: A New HSV Thymidine Kinase Mutation Associated With Resistance.
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DOI：
10.1093/jpids/pis009
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发表时间：
2012-06
影响因子：
3.2
通讯作者：
Andrew H. Karaba;Laura K Cohen;Taly Glaubach;Sarah J Kopp;J. Reichek;Hawke H. Yoon;Xiaotian Zheng;W. Muller
中科院分区：
文献类型：
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作者：
Andrew H. Karaba;Laura K Cohen;Taly Glaubach;Sarah J Kopp;J. Reichek;Hawke H. Yoon;Xiaotian Zheng;W. Muller
背景单纯疱疹病毒对阿昔洛韦的耐药性在免疫功能低下的患者中有很好的描述。长期感染和复发的管理可能是有问题的。方法1例神经母细胞瘤患者在化疗后不久发生了可能的原发性疱疹性龈口炎，在接受阿昔洛韦治疗期间扩散到眼睛。在治疗开始后，从不同的地点连续获得病毒分离株，并通过空斑减少和平板接种效率测定来测试对阿昔洛韦和膦甲酸的敏感性。对每个分离株的胸苷激酶和DNA聚合酶基因进行测序。结果从咽拭子、口腔病变和结膜分离的初始菌株在治疗后13天内对阿昔洛韦耐药。随后的分离株，而膦甲酸最初是阿昔洛韦敏感，但随后记录了一个阿昔洛韦耐药分离株的重新激活，而对阿昔洛韦抑制。基因型分析确定了以前未报告的UL23突变在一些耐药菌株。在UL30中鉴定的氨基酸变化均与抗性无关。结论：单纯疱疹病毒分离株的表型和基因型抗病毒耐药性可能因不同的隔室而异，并随着时间的推移，在个别免疫受损的主机，突出了从所有网站获得文化的重要性。对于从一线治疗无效的高危患者中获得的分离株，应考虑进行表型耐药检测。在某些情况下，可以考虑使用多种抗病毒药物的经验性联合治疗。
BACKGROUND Herpes simplex virus resistance to acyclovir is well described in immune-compromised patients. Management of prolonged infection and recurrences in such patients may be problematic. METHODS A patient with neuroblastoma developed likely primary herpes gingivostomatitis shortly after starting a course of chemotherapy, with spread to the eye during treatment with acyclovir. Viral isolates were serially obtained from separate sites after treatment was begun and tested for susceptibility to acyclovir and foscarnet by plaque reduction and plating efficiency assays. The thymidine kinase and DNA polymerase genes from each isolate were sequenced. RESULTS Initial isolates from a throat swab, an oral lesion, and conjunctiva were resistant to acyclovir within 13 days of treatment. Subsequent isolates while on foscarnet were initially acyclovir-susceptible, but reactivation of an acyclovir-resistant isolate was subsequently documented while on acyclovir suppression. Genotypic analysis identified a previously unreported UL23 mutation in some resistant isolates. None of the amino acid changes identified in UL30 were associated with resistance. CONCLUSIONS Phenotypic and genotypic antiviral resistance of herpes simplex isolates may vary from different compartments and over time in individual immune-compromised hosts, highlighting the importance of obtaining cultures from all sites. Phenotypic resistance testing should be considered for isolates obtained from at-risk patients not responding to first-line therapy. Empiric combination treatment with multiple antivirals could be considered in some situations.