Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Laboratory of Viral Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Transpl Infect Dis. 2020 Aug;22(4):e13336. doi: 10.1111/tid.13336. Epub 2020 Jun 10.
Seasonal influenza causes significant morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. In this population, influenza virus can replicate for prolonged periods, despite neuraminidase inhibitor treatment, leading to resistance and treatment failure. Baloxavir targets the influenza polymerase and may be an effective treatment option in these patients.
We used baloxavir to treat five allogeneic SCT recipients that were still symptomatic and shedding influenza virus after completing one or more treatment courses of oseltamivir and characterized the viral isolates before and during treatment.
Two patients were infected with influenza A/H1pdm09 carrying a neuraminidase variant (H275Y) linked to oseltamivir resistance. Both these two patients were successfully treated with baloxavir. Of the three patients infected with wild-type influenza virus, two cleared the virus after baloxavir treatment, while the third patient developed the polymerase I38T variant linked to baloxavir resistance.
Our data suggest that baloxavir treatment can be effective in treating neuraminidase inhibitor-resistant influenza in profoundly immunocompromised patients. Randomized clinical trials are needed to define the role of baloxavir alone and combined with oseltamivir for the treatment of influenza in SCT recipients and other immunocompromised populations.
季节性流感可导致异基因造血干细胞移植（SCT）受者发生严重的发病率和死亡率。在该人群中，流感病毒可在神经氨酸酶抑制剂治疗的情况下持续复制很长时间，导致耐药性和治疗失败。巴洛沙韦针对流感聚合酶，可能是这些患者的有效治疗选择。
我们使用巴洛沙韦治疗了五例仍有症状且在完成一个或多个奥司他韦疗程后仍在排出流感病毒的异基因 SCT 受者，并在治疗前后对病毒分离株进行了特征分析。
两名患者感染了携带与奥司他韦耐药相关的神经氨酸酶变异（H275Y）的甲型流感 A/H1pdm09。这两名患者均成功接受了巴洛沙韦治疗。在感染野生型流感病毒的三名患者中，有两名在接受巴洛沙韦治疗后清除了病毒，而第三名患者则出现了与巴洛沙韦耐药相关的聚合酶 I38T 变异。
我们的数据表明，巴洛沙韦治疗可有效治疗严重免疫抑制患者的神经氨酸酶抑制剂耐药性流感。需要进行随机临床试验来确定巴洛沙韦单独或与奥司他韦联合用于治疗 SCT 受者和其他免疫抑制人群中的流感的作用。
