A retrospective observational study of the treatment of a nosocomial infection caused by oseltamivir-resistant influenza virus A with baloxavir marboxil

BackgroundNosocomial (hospital-acquired) influenza A virus infection is a very important clinical issue. The objective of this study is to describe the effect of baloxavir marboxil in controlling an outbreak of this infection.MethodsA retrospective observational study was performed to assess the effectiveness of baloxavir marboxil in the treatment of nosocomial infections caused by oseltamivir-resistant influenza virus A.ResultsIn September 2019, there was an outbreak of nosocomial influenza A(H1N1)pdm09 viral infection in one out of three facility wards for inpatients at the Okinawa Nanbu Regional Center for Children with Special Needs. Symptomatic staff members were kept off duty until they remained afebrile for 2 days. Prophylactic oseltamivir was administered to inpatients (n = 37) and to staff members (n = 16) who voluntarily requested the drug. However, both inpatients and staff members showed influenza A infection during prophylactic use of oseltamivir. The A(H1N1)pdm09 virus sample obtained from one patient was shown to be oseltamivir-resistant. After administration of baloxavir marboxil, the nosocomial outbreak gradually ceased. Moreover, the time (hours) to alleviation of fever in the oseltamivir group (n = 11) and baloxavir marboxil group (n = 13) was significantly different (p = 0.0034).ConclusionOur report provides evidence for the usefulness of baloxavir marboxil in treating influenza A patients who have received prophylactic doses of oseltamivir. This is the first report describing the successful use of baloxavir marboxil for of a nosocomial outbreak caused by oseltamivir-resistant influenza A virus.     

Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective

Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008-2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC(50)s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC(50) >3 interquartile ranges (IQR) from the 75(th) percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance.     

奥司他韦治疗60例疑似甲型流感的药效评估

目的：探讨奥司他韦抗病毒药治疗疑似甲流的安全性、有效性。方法：将60例疑似甲流患者随机平均分成2组：实验组口服奥司他韦治疗;对照组口服利巴韦林治疗。评估比较2组的流感症状缓解情况及症状消失时间。结果：实验组的临床有效率93.33%,明显高于对照组的70.00%（P〈0.05）。实验组的退热时间以及其他主要症状平均消失时间明显短于对照组（P〈0.05）,实验组治疗5d后发热、咽喉痛、鼻塞、咳嗽、头痛、肌肉关节痛、发冷/出汗、乏力等症状的缓解率明显高于对照组（P〈0.05）;实验组的不良反应发生率13.33%,明显低于对照组36.67%（P〈0.05）。结论：奥司他韦抗病毒用于治疗疑似甲流安全、有效,且效果好于利巴韦林。     

In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011–2012 season in Japan

The neuraminidase inhibitors oseltamivir phosphate (Tamiflu^®), zanamivir (Relenza^®), laninamivir octanoate (Inavir^®), and peramivir (Rapiacta^®) have been available for the treatment of influenza in Japan since 2010. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC₅₀) of each drug for influenza virus isolates from the 2011–2012 influenza season.Specimens were obtained from patients prior to treatment. Viral isolation was done using Madine-Darby canine kidney cells, and the type and subtype of influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate. The lineage of influenza B virus was determined by direct sequencing of the hemagglutinin gene.Influenza A(H3N2) and influenza B viruses were isolated in 283 and 42 patients, respectively, while no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC₅₀ value exceeding 50 nM for any of the neuraminidase inhibitors. IC₅₀ values for A(H3N2) were similar between the 2010–2011 and 2011–2012 seasons. In contrast, the IC₅₀ values for influenza B viruses in the 2011–2012 season to the four drugs were significantly lower than those found in the 2010–2011 season. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC₅₀ values to increase in Japan at present.     

HPLC测定3厂家磷酸奥司他韦胶囊的溶出度

目的 采用HPLC法考察3厂家磷酸奥司他韦胶囊的溶出度,为药品的采购和临床用药提供参考.方法 采用转篮法进行体外溶出度实验,以HPLC-UV法测定含量,计算累计溶出百分率;以威布尔方程拟合溶出度参数T50、Td、T80、m,再利用f2相似因子法对3厂家药物的溶出行为进行分析.结果 3个厂家磷酸奥司他韦胶囊的体外溶出度均符合2010版《中国药典》的规定,但溶出参数T20、Td、T80、m存在一定差异(P＜0.01).结论 不同厂家生产的磷酸奥司他韦胶囊的溶出参数存在一定差异,临床用药时应加以注意.     

Recent changes in the trends of seasonal influenza outbreaks in the Nagano Prefectural area of Japan: an oseltamivir effect?

We carried out a study to assess the pharmacological role of oseltamivir in the regulation of influenza epidemics in Japan, examining data for the years 1998 to 2006 from Nagano Prefecture. Oseltamivir is effective for the treatment of influenza, and its use in Japan has increased in the 3 years from 2003 to 2006. We found that, in the Nagano Prefectural area, the peak in the number of influenza infections showed a deviation to later periods after the 2003 season. and after 2003, it also took a longer time to reach the end of the seasonal epidemics of influenza infections compared with data from 1998 to 2002. To prevent influenza outbreaks having a long duration, we believe that the period of isolation in patients receiving anti-influenza drugs has to be reconsidered.     

小儿肺热咳喘口服液联合奥司他韦治疗小儿病毒性肺炎的临床研究

目的探讨小儿肺热咳喘口服液联合磷酸奥司他韦颗粒治疗小儿病毒性肺炎的临床疗效。方法选取2017年3月—2018年2月中国人民解放军第306医院收治的病毒性肺炎患儿124例为研究对象,按照随机数字表法分为对照组和治疗组,每组各62例。对照组口服磷酸奥司他韦颗粒,体质量15 kg 30 mg/次,15～23 kg 45 mg/次,23～40 kg 60 mg/次,40 kg 75 mg/次,2次/d。治疗组在对照组治疗的基础上口服小儿肺热咳喘口服液,1～3岁,10m L/次,3次/d;4～7岁,10m L/次,4次/d;8～12岁,20 mL/次,3次/d。两组患儿均连续治疗5 d。观察两组的临床疗效,比较两组的临床改善情况和细胞因子水平。结果治疗后,对照组和治疗组的总有效率分别为80.65%、93.55%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组体温恢复正常时间、咳嗽消失时间、肺啰音消失时间短于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组C反应蛋白(CRP)、白细胞介素-6(IL-6)、基质金属蛋白酶9(MMP-9)、肿瘤坏死因子α(TNF-α)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组细胞因子水平明显低于对照组,两组比较差异具有统计学意义(P0.05)结论小儿肺热咳喘口服液联合磷酸奥司他韦颗粒治疗小儿病毒性肺炎具有较好的临床疗效,能改善临床症状,调节细胞因子水平,具有一定的临床推广应用价值。