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.     

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。     

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.     

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。     

11例甲型H1N1流感患者临床分析

目的探讨甲型H1N1流感患者的临床特点及其转归。方法对11例甲型H1N1流感患者进行隔离治疗,分析其流行病学、临床表现、实验室检查、治疗效果及临床转归等方面资料。结果甲型H1N1流感好发于年轻人,发热、咳嗽及咽部不适为主要临床症状,部分患者出现白细胞减少及低钾血症,早期应用抗病毒治疗后,平均1.5d后体温正常,平均6.6d后咽拭子病毒转阴,8.3d痊愈;治疗中未见明显药物不良反应出现。结论甲型H1N1流感轻症患者早期抗病毒治疗有助于缩短病程,使用奥司他韦无论是进口的达菲,还是我国的军科奥韦治疗甲型H1N1流感均是安全、有效的。     

帕拉米韦治疗儿童甲型流感病毒感染的临床疗效

目的探讨帕拉米韦在治疗儿童甲型流感病毒感染的临床疗效及安全性。 方法将2016年6月至2017年1月首都医科大学附属北京儿童医院收治的确诊甲型流感患儿共300例,采用前瞻性研究,分为帕拉米韦治疗组（150例）和奥司他韦治疗组（150例）。观察两组患儿治疗后发热缓解时间、症状缓解时间及不良反应。 结果帕拉米韦治疗组和奥司他韦治疗组患儿中位症状缓解时间分别为27.9 h和42.7 h,差异具有统计学意义（t=－18.325、P < 0.001）;两组患儿中位发热缓解时间分别为17.8 h和22.3 h,差异具有统计学意义（t =－9.365、P < 0.001）。两组病例均无并发症发生。帕拉米韦治疗组和奥司他韦治疗组患儿不良反应发生率分别为4.0%和7.3%,差异无统计学意义（χ²= 1.349、P= 0.246）。两组患儿不良反应均未经特殊处理自行缓解消退。 结论帕拉米韦治疗儿童甲型流感病毒感染可快速有效缓解症状、缩短发热持续时间,安全性及耐受性良好。     

中医辨证治疗甲型H1N1流感疗效观察

目的：探讨中医治疗甲型H1N1流感疗效。方法：回顾性分析我院2009年9月至2010年1月间46例甲型H1N1流感病例，随机分为治疗组和对照组，每组23例，治疗组在奥司他韦治疗基础上给予中医辨证治疗；对照组仅给予奥司他韦治疗。结果：两组，6-有效率为100％，治疗组显效率（78．26％）优于对照组（47．83％）。结论：中医辨证治疗甲型H1N1流感疗效显著。     

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.