流感感染早期抗病毒治疗
美国疾病预防控制中心 (CDC) 推荐,对于患有严重、有并发症的或进展性疾病或需要住院的确诊或疑似流感患者以及并发症风险较高的患者,应尽快给予抗病毒治疗。[109]Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. February 2018 [internet publication].https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm[110]Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-24.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21248682?tool=bestpractice.com[111]Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2018 Dec 19.[Epub ahead of print].https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy866/5251935http://www.ncbi.nlm.nih.gov/pubmed/30566567?tool=bestpractice.com虽然神经氨酸酶抑制剂已被美国食品药品监督管理局 (FDA) 批准用于治疗无并发症的急性疾病,但指南常常推荐将这些药物用于治疗有并发症的疾病以及存在并发症风险的患者。当地指南可能存在差异,治疗前应当查阅。[112]Public Health England. Influenza: treatment and prophylaxis using anti-viral agents. October 2017.https://www.gov.uk/government/publications/influenza-treatment-and-prophylaxis-using-anti-viral-agents
神经氨酸酶抑制剂(扎那米韦、奥司他韦和帕拉米韦)可对甲型和乙型流感均有抗病毒活性。[113]Jefferson T, Jones M, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ. 2009;339:b5106.http://www.bmj.com/content/339/bmj.b5106.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19995812?tool=bestpractice.com[114]Shun-Shin M, Thompson M, Heneghan C, et al. Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. BMJ. 2009;339:b3172.http://www.bmj.com/content/339/bmj.b3172.longhttp://www.ncbi.nlm.nih.gov/pubmed/19666987?tool=bestpractice.com[109]Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. February 2018 [internet publication].https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm[115]Doll MK, Winters N, Boikos C, et al. Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: a systematic review of systematic reviews and/or meta-analyses. J Antimicrob Chemother. 2017 Nov 1;72(11):2990-3007.http://www.ncbi.nlm.nih.gov/pubmed/28961794?tool=bestpractice.com[116]Venkatesan S, Myles PR, Leonardi-Bee J, et al. Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an individual participant data metaanalysis. Clin Infect Dis. 2017 May 15;64(10):1328-1334.http://www.ncbi.nlm.nih.gov/pubmed/28199524?tool=bestpractice.com奥司他韦和扎那米韦对其他方面均健康的成人流感症状具有一定疗效,[117]Jackson RJ, Cooper KL, Tappenden P, et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: a systematic review. J Infect. 2011;62:14-25.http://www.ncbi.nlm.nih.gov/pubmed/20950645?tool=bestpractice.com [
]What are the benefits and harms of neuraminidase inhibitors for the treatment of influenza in otherwise healthy adults?https://cochranelibrary.com/cca/doi/10.1002/cca.990/full显示答案 并被广泛用于治疗 2009 年甲型 H1N1 流感。[113]Jefferson T, Jones M, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ. 2009;339:b5106.http://www.bmj.com/content/339/bmj.b5106.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19995812?tool=bestpractice.com[118]Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014;(4):CD008965.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24718923?tool=bestpractice.com[119]Heneghan CJ, Onakpoya I, Thompson M, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2547.http://www.bmj.com/content/348/bmj.g2547.longhttp://www.ncbi.nlm.nih.gov/pubmed/24811412?tool=bestpractice.com[120]Jefferson T, Jones M, Doshi P, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2545.http://www.bmj.com/content/348/bmj.g2545.longhttp://www.ncbi.nlm.nih.gov/pubmed/24811411?tool=bestpractice.com 然而,应用奥司他韦是否降低健康成人和儿童并发症存在广泛争议。[113]Jefferson T, Jones M, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ. 2009;339:b5106.http://www.bmj.com/content/339/bmj.b5106.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19995812?tool=bestpractice.com[121]Cohen D. Complications: tracking down the data on oseltamivir. BMJ. 2009;339:b5387. [Erratum in: BMJ. 2010;340:c406.]http://www.ncbi.nlm.nih.gov/pubmed/19995818?tool=bestpractice.com[122]Doshi P. Neuraminidase inhibitors - the story behind the Cochrane review. BMJ. 2009;339:b5164.http://www.ncbi.nlm.nih.gov/pubmed/19995813?tool=bestpractice.com[123]Jefferson T, Doshi P, Thompson M, et al. Ensuring safe and effective drugs: who can do what it takes? BMJ. 2011;342:c7258.http://www.ncbi.nlm.nih.gov/pubmed/21224325?tool=bestpractice.com 一些观察性研究表明,奥司他韦可降低季节性流感住院患者的死亡率。[124]Uyeki T. Antiviral treatment for patients hospitalized with 2009 pandemic influenza A (H1N1). N Engl J Med. 2009;361:e110.http://www.ncbi.nlm.nih.gov/pubmed/19923564?tool=bestpractice.com 一项 meta 分析的发现显示,奥司他韦可适当缩短成人流感的临床症状恢复时间,但是增加了恶心和呕吐的发生率。[125]Dobson J, Whitley RJ, Pocock S, et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385:1729-1737.http://www.ncbi.nlm.nih.gov/pubmed/25640810?tool=bestpractice.com
M2 抑制剂金刚烷胺和金刚乙胺仅对甲型流感有抗病毒活性。 [
]In children with clinically or serologically confirmed influenza A, do amantadine and rimantadine improve outcomes?https://cochranelibrary.com/cca/doi/10.1002/cca.21/full显示答案 [
]If there is an outbreak of influenza A in the community, do amantadine and rimantadine given prophylactically prevent the development of influenza in children?https://cochranelibrary.com/cca/doi/10.1002/cca.25/full显示答案 金刚乙胺不应该用作一线治疗已成为专家共识,因为病毒对金刚烷胺的交叉耐药性高。因为耐药毒株的增加,关于季节性耐药模式的抗病毒治疗,临床医生应从当地权威机构征求建议。[109]Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. February 2018 [internet publication].https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
无论是12岁以上的儿童还是成人。 若症状发作48小时内口服奥司他韦和吸入扎那米韦均可减少流感的持续时间。[126]Jefferson T, Demicheli V, Rivetti D, et al. Antivirals for influenza in healthy adults: systematic review. Lancet. 2006;367:303-313.http://www.ncbi.nlm.nih.gov/pubmed/16443037?tool=bestpractice.com[127]Wang K, Shun-Shin M, Gill P, et al. Neuraminidase inhibitors for preventing and treating influenza in children (published trials only). Cochrane Database Syst Rev. 2012;(1):CD002744.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002744.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22513907?tool=bestpractice.com最大获益是在症状出现的24~30小时进行治疗。[126]Jefferson T, Demicheli V, Rivetti D, et al. Antivirals for influenza in healthy adults: systematic review. Lancet. 2006;367:303-313.http://www.ncbi.nlm.nih.gov/pubmed/16443037?tool=bestpractice.com[128]Stiver G. The treatment of influenza with antiviral drugs. CMAJ. 2003;168:49-56.http://www.cmaj.ca/content/168/1/49.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12515786?tool=bestpractice.com[129]Cooper NJ, Sutton AJ, Abrams KR, et al. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ. 2003;326:1235.http://www.bmj.com/content/326/7401/1235.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12791735?tool=bestpractice.com[130]Heinonen S, Silvennoinen H, Lehtinen P, et al. Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial. Clin Infect Dis. 2010;51:887-894.http://cid.oxfordjournals.org/content/51/8/887.longhttp://www.ncbi.nlm.nih.gov/pubmed/20815736?tool=bestpractice.com
开具处方时,奥司他韦和扎那米韦应在症状出现 2 天内给药,连续给予 5 天。帕拉米韦给药方式为单次输注,也应在症状出现 2 天内给药。[109]Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. February 2018 [internet publication].https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm[110]Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-24.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21248682?tool=bestpractice.com对于不能服用口服或吸入型神经氨酸酶抑制剂的患者,可推荐使用帕拉米韦。
奥司他韦成人耐受性良好,儿童可能会引起呕吐。 扎那米韦比奥司他韦在减少成人呼吸系统并发症方面证据较少。
奥司他韦的药物安全性警告:2006年11月后有与其使用相关的自我伤害和谵妄的报告。 警告指出,流感患者特别是儿童,服用奥司他韦后自我伤害和谵妄的风险增加,应该密切监测异常行为的征象。
对于出现流感表现但无并发症的孕妇,如果没有全身性疾病的证据,可给予扎那米韦或奥司他韦。[110]Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-24.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21248682?tool=bestpractice.com 尽管两种药物都可以使用,鉴于给药方式不同,首选扎那米韦。 对于哺乳期妇女,奥司他韦优于扎那米韦。 小于1岁儿童出现季节性流感症状用奥司他韦治疗。[110]Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-24.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21248682?tool=bestpractice.com