Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias (CIBERES), Spain.
J Clin Virol. 2011 Feb;50(2):114-8. doi: 10.1016/j.jcv.2010.10.007. Epub 2010 Nov 11.
Pandemic 2009 influenza A/H1N1 (H1N1v) is resistant to adamantanes, leaving neuraminidase inhibitors as the only therapeutic option. Other mutations are considered to be associated with virulence and clinical severity. However, out of the surveillance programs, few studies analyze the presence of resistance/virulent H1N1v variants in certain clinical circumstances.
To define the frequency and role of resistance and virulence mutations in a specific clinical circumstance-in patients with persistent infection by H1N1v.
Observational study of patients with persistent H1N1v infection admitted to our hospital.
NAI-resistance mutations were detected in 14.3% of cases with persistent infection (2/14), and in none of the non-persistent controls (0/15). These cases were initially infected with susceptible variants that acquired resistance at different time-points after therapy with oseltamivir (OTV). The first case (case 2) was an HIV-positive patient who rapidly acquired resistance 9 days after diagnosis (6 days on OTV) and whose infection resolved after standard OTV therapy. The second case (case 3) was a patient with chronic lymphocytic leukemia [corrected] and the longest viral persistence (59 days). The resistance mutation was detected in the specimen taken on day 37 after diagnosis (30 days on OTV). Once the resistance mutation was identified, OTV was substituted by zanamivir and the infection resolved. In addition to mutations encoding resistance, variants associated with virulence were also sought. The D225G mutation was not found in any case, whereas the D225E variant was identified in three persistent cases but also in two non-persistent ones. In one patient, the D225E substitution coincided with the H275 resistant mutation.
NAI-resistance mutations were detected, at rather different paces, in non-severe immunosuppressed cases with persistent infection by influenza A/H1N1v.
大流行 2009 年甲型 H1N1（H1N1v）对金刚烷胺具有耐药性，使得神经氨酸酶抑制剂成为唯一的治疗选择。其他突变被认为与毒力和临床严重程度有关。然而，在监测计划之外，很少有研究分析在某些临床情况下抗药性/毒力变异的 H1N1v 变体的存在。
在特定的临床情况下-持续性感染 H1N1v 的患者中，确定耐药性和毒力突变的频率和作用。
对我院收治的持续性 H1N1v 感染患者进行观察性研究。
在持续性感染（14 例中有 2 例，占 14.3%）的病例中检测到神经氨酸酶抑制剂耐药性突变，而非持续性对照组（15 例中无 0 例）中未检测到。这些病例最初感染的是对奥司他韦（OTV）敏感的变体，在治疗后不同时间点获得了耐药性。第一例（病例 2）是 HIV 阳性患者，在诊断后 9 天（OTV 治疗 6 天后）迅速获得耐药性，其感染在标准 OTV 治疗后得到解决。第二例（病例 3）是一名慢性淋巴细胞白血病患者[更正]，病毒持续时间最长（59 天）。在诊断后第 37 天（OTV 治疗 30 天后）采集的标本中检测到耐药性突变。一旦发现耐药性突变，就将 OTV 替换为扎那米韦，感染得到解决。除了编码耐药性的突变外，还寻找与毒力相关的变体。在任何病例中均未发现 D225G 突变，而在 3 例持续性病例和 2 例非持续性病例中发现了 D225E 变体。在一名患者中，D225E 取代与 H275 耐药性突变同时发生。
在非严重免疫抑制患者中，以不同的速度检测到对神经氨酸酶抑制剂的耐药性突变，这些患者持续性感染了甲型 H1N1v。
