Antivirals for influenza: Strategies for use in pediatrics

Pediatric Drugs

Volumn 12, Issue 5, 2010, Pages 285-299

  Smith, Steven M ^a,b   Gums, John G ^a,b  

^a UNIVERSITY OF FLORIDA HEALTH   (United States)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

adamantanes, therapeutic use; amantadine, therapeutic use; antivirals, therapeutic use; influenza virus infections, treatment; influenza virus infections, prevention; neuraminidase inhibitors, therapeutic use; oseltamivir, therapeutic use; peramivir, therapeutic use; research and development; rimantadine, therapeutic use; zanamivir, therapeutic use

Indexed keywords

ADAMANTANE DERIVATIVE; AMANTADINE; ANTIBIOTIC AGENT; ANTIVIRUS AGENT; CYANOVIRIN N; DAS 181; FAVIPIRAVIR; LANINAMIVIR; MONOCLONAL ANTIBODY; OSELTAMIVIR; PARACETAMOL; PERAMIVIR; PHYSOSTIGMINE; RIBAVIRIN; RIMANTADINE; SIALIDASE INHIBITOR; SMALL INTERFERING RNA; TARIBAVIRIN; UNCLASSIFIED DRUG; ZANAMIVIR;

ABDOMINAL PAIN; ANOREXIA; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ANXIETY DISORDER; BACTERIAL INFECTION; BEHAVIOR; BRONCHOSPASM; CLINICAL TRIAL; DELIRIUM; DEPRESSION; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG FATALITY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG OVERDOSE; FATIGUE; FEVER; GENE MUTATION; HALLUCINATION; HEALTH CARE COST; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLUENZA; INFLUENZA A (H1N1); INFLUENZA A (H3N2); INFLUENZA A (H5N1); INFLUENZA B; INFLUENZA VACCINATION; INFLUENZA VIRUS; INFLUENZA VIRUS A H1N1; INFLUENZA VIRUS A H5N1; INSOMNIA; IRRITABILITY; JAPAN; LUNG FUNCTION; MORBIDITY; MORTALITY; NAUSEA; NERVOUSNESS; NEUROLEPTIC MALIGNANT SYNDROME; NONHUMAN; OTITIS MEDIA; PATIENT COMPLIANCE; PNEUMONIA; PRESCRIPTION; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; SEASONAL INFLUENZA; SEIZURE; SIDE EFFECT; SINGLE DRUG DOSE; SUICIDE; VIRUS REPLICATION; VIRUS STRAIN; VOMITING; WITHDRAWAL SYNDROME; XEROSTOMIA;

ADAMANTANE; ANIMALS; ANTIVIRAL AGENTS; CHILD; DRUG THERAPY, COMBINATION; HUMANS; INFLUENZA, HUMAN; NEURAMINIDASE; ORTHOMYXOVIRIDAE; PEDIATRICS;

EID: 77956330032     PISSN: 11745878     EISSN: 11792019     Source Type: Journal    
DOI: 10.2165/11532530-000000000-00000     Document Type: Review

References (135)

1. Thompson WW, Shay DK, Weintrab E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179-186
2. Thompson WW, Shay DK, Weintrab E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004; 292: 1333-1340
3. Cox FM, Cobb MM, Chua WQ, et al. Cost of treating influenza in emergency department and hospital settings. Am J Manag Care 2000; 6 (2): 205-214
4. Couch RB. Prevention and treatment of influenza. N Engl J Med 2000; 343 (24): 1778-1787
5. Centers forDisease Control and Prevention (CDC). Prevention and control of influenza: recommendations of the advisory committee on immunization practices (ACIP), 2007. MMWR Recomm Rep 2007; 56: 1-54
6. Allen U. The battle against influenza: the role of neuraminidase inhibitors in children. Can J Infect Dis 2000; 11 (6): 295-298
7. Glezen WP. Modifying clinical practices to manage influenza in children effectively. Pediatr Infect Dis J 2008; 27: 738-743
8. Bhat N, Wright JG, Broder KR, et al. Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005; 353: 2559-2567
9. Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza.Clinical aspects of pandemic 2009 influenzaA (H1N1) virus infection. N Engl J Med 2010; 362: 1708-1719
10. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of influenza: recommendations for influenza immunization of children, 2007-2008. Pediatrics 2008; 121: e1016-31
11. Harper SA, Fukuda K, Uyeki TM, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2004; 53 (RR-6): 1-40
12. Center for Disease Control and Prevention. Influenza vaccination coverage among children aged 6-59 months: six immunization information system sentinel sites, United States, 2006-2007 influenza season. MMWR 2007; 56 (37): 963-965
13. Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. Centers forDisease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). MMWR ecomm Rep 2008; 57 (RR-7): 1-60
14. Maeda T, Shintani Y, Miyamoto H, et al. Prophylactic effect of inactivated influenza vaccine on young children. Pediatr Int 2002; 44: 43-46
15. Maeda T, Shintani Y, Nakano K, et al. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Pediatr Int 2004; 46: 122-125
16. Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007; 356: 685-696
17. Shuler CM, Iwamoto M, Bridges CB, et al. Vaccine effectiveness against medically attended, laboratory-confirmed influenza among children aged 6 to 59 months, 2003-2004. Pediatrics 2007; 119: e587-95
18. Allison MA, Daley MF, Crane LA, et al. Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season. J Pediatr 2006; 149: 755-762
19. Ritzwoller DP, Bridges CB, Shetterly S, et al. Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Pediatrics 2005; 116: 153-159
20. Nicholson KG. Clinical features of influenza. Semin Respir Infect 1992; 7 (1): 26-37
21. Hermsen ED, Rupp ME. Influenza. In: Dipiro JT, Talbert R, Yee G, et al., editors. Pharmacotherapy: a pathophysiologic approach. 7th ed.New York: McGraw Hill Medical, 2008: 1791-1799
22. Wright P. Influenza viruses. In: Kliegman RM, Behrman RE, Jenson HB, et al., editors. Nelson textbook of pediatrics. 8th ed. Philadelphia (PA): Saunders, 2007: 901-903
23. Aoki FY, Macleod MD, Paggiaro P, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003; 51: 123-129
24. McGeer A, Green KA, Plevneshi A, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007; 45: 1568-1575
25. Symmetrel® (amantadine hydrochloride, USP) [package insert]. Chadds Ford (PA): Endo Pharmaceuticals, 2007
26. Flumadine® (rimantadine hydrochloride) [prescribing information]. St Louis (MO): Forest Laboratories Inc., 2007 Apr
27. RELENZA® (zanamivir for inhalation) [prescribing information]. Research Triangle Park (NC): GlaxoSmithKline, 2008 Oct
28. TAMIFLU® (oseltamivir phosphate) [prescribing information]. Nutley (NJ): Roche Laboratories Inc., 2006 Nov
29. BuiM, Whittaker G, Helenius A. Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 1996; 70: 8391-8401
30. Sugrue RJ, Hay AJ. Structural characteristics of the M2 protein of influenza A viruses: evidence that it forms a tetrameric channel. Virology 1991; 180: 617-624
31. Stiver G. The treatment of influenza with antiviral drugs. CMAJ2003; 168 (1): 49-57
32. Centers for Disease Control and Prevention (CDC). Interim recommendations for the use of influenza antiviral medications in the setting of oseltamivir resistance among circulating influenza A (H1N1) viruses, 2008-09 influenza season [online]. Available from URL: professionals/antivirals/recommendations. htm [Accessed 2009 Apr 22]
33. Kitamoto O. Therapeutic effectiveness of amantadine hydrochloride in influenza A2: double blind studies. Jpn J Tuberc Chest Dis 1968; 15: 17-26
34. Gallbraith AW, Oxford JS, Schild GC, et al. Therapeutic effect of 1- adamantanamine hydrochloride in naturally occurring influenza A2-Hong Kong infection: a controlled double-blind study. Lancet 1971; 2 (7716): 113-115
35. Kitamoto O. Therapeutic effectiveness of amantadine hydrochloride in naturally occurring Hong Kong influenza: double-blind studies. Jpn J Tuberc Chest Dis 1971; 17: 1-7
36. Gallbraith AW, Schild GC, Potter CW, et al. The therapeutic effect of amantadine in influenza occurring during the winter of 1971-2 assessed by double-blind study. J R Coll Gen Pract 1973; 23: 34-37
37. Alves Galva o MG, Rocha Crispino Santos MA, Alves da Cunha AJL. Amantadine and rimantadine for influenza A in children and the elderly. Cochrane Database Syst Rev 2008; (1): CD002745
38. Hall CB, Dolin R, Gala CL, et al. Children with influenza A infection: treatment with rimantadine. Pediatrics 1987; 80: 275-282
39. Thompson J, Fleet W, Lawrence E, et al.Acomparison of acetaminophen and rimantadine in the treatment of influenza A infection in children. J Med Virol 1987; 21: 249-255
40. Vernier VG, Harmon JB, Stump JM, et al. The toxicologic and pharmacologic properties of amantadine hydrochloride. Toxicol Appl Pharmacol 1969; 15: 642-665
41. Strawn JR, Keck PE, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry 2007; 164 (6): 870-876
42. Shobugawa Y, Saito R, Sato I, et al. Recurrence and persistence of fever in children who developed amantadine-resistant influenza viruses after treatment. Tohoku J Exp Med 2008; 214: 129-138
43. Pinto LH, Holsinger LJ, Lamb RA. Influenza virus M2 protein has ion channel activity. Cell 1992; 69: 517-528
44. Holsinger LJ, Nichani D, Pinto LH, et al. Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol 1994; 68: 1551-1563
45. Englund JA, Champlin RE, Wyde PR, et al. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis 1998; 26: 1418-1424
46. Bright RA, Medina M-J, Xu X, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005; 366: 1175-1181
47. Bright RA, Shay DK, Shu B, et al. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 2006; 295 (8): 891-894
48. Centers for Disease Control and Prevention (CDC). Update: influenza activity . United States, September 30, 2007-April 5, 2008 and composition of the 2008-09 influenza vaccine. MMWR Morb Mortal Wkly Rep 2008; 57 (15): 404-409
49. Centers for Disease Control and Prevention (CDC). Weekly report: influenza summary update week 14, 2008-2009 season [online]. Available from URL: http://www.cdc.gov/flu/weekly/ [Accessed 2009 Apr 22]
50. Centers forDisease Control and Prevention (CDC). Interim guidance on antiviral recommendations for patients with confirmed or suspected swine influenzaA( H1N1) virus infection and close contacts [online].Available fromURL: http://www.cdc.gov/swineflu/recommendations.htm [Accessed 2009 Apr 28]
51. Itzstein M. The war against influenza: discovery and development of sialidase inhibitors. Nat Rev Drug Discov 2007; 6 (12): 967-974
52. Kim CU, Lew W, Williams MA, et al. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 1997; 119: 681-690
53. Varghese JN, Laver WG, Colman PM. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9Åresolution. Nature 1983; 303: 35-40
54. Moscona A. Neuraminidase inhibitors for influenza. NEngl J Med 2005; 353: 1363-1373
55. Dines GD, Bethell R, Daniel M. Preclinical development of low toxicity drugs: focus on zanamivir, an anti-influenza drug. Drug Saf 1998; 19 (3): 233-241
56. Hedrick JA, Barzilai A, Behre U, et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J 2000; 19: 410-417
57. Sugaya N, Tamura D, Yamazaki M, et al. Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis 2008; 47: 339-345
58. Hayden FG, Gubareva LV, Monto AS, et al. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med 2000; 343 (18): 1282-1289
59. Peng AW, Hussey EK, Rosolowski B, et al. Pharmacokinetics and tolerability of a single inhaled dose of zanamivir in children. Curr Ther Res Clin Exp 2000; 61: 33-46
60. Imuta F, Toyoda M, Toyoda T. New application method of zanamivir with a straw. Pediatr Int 2003; 45: 366-367
61. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza. JAMA2000; 283 (8): 1016-1024
62. 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-analysis of randomized controlled trials. BMJ 2003; 326: 1235-1240
63. Roche Pharmaceuticals. Roche update on Tamiflu for pandemic influenza preparedness [online]. Available from URL: 2007-04-26 [Accessed 2008 Sep 13]
64. Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001; 20: 127-133
65. Hayden FG, Belshe R, Villanueva C, et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis 2004; 189 (3): 440-449
66. US FDA. Dear healthcare professional letter: Tamiflu® (oseltamivir) 2003 [online]. Available from URL: 2003/safety03.htm#tamiflu [Accessed 2008 Oct 1]
67. Whitley RJ, Monto AS. Prevention and treatment of influenza in high-risk groups: children, pregnant women, immunocompromised hosts, and nursing home residents. J Infect Dis 2006; 194 Suppl. 2: S133-8
68. Tamura D, Miura T, Kikuchi Y. Oseltamivir phosphate in infants under 1 year of age with influenza infection [letter]. Pediatr Int 2005; 47: 484
69. Siedler K, Skopnik H. Oseltamivir for treatment of influenza in infants less than one year: a retrospective analysis. Pediatr Infect Dis J 2010; 29: 495-498
70. Centers forDisease Control and Prevention (CDC). Termination of the emergency use authorization (EUA) ofmedical products and devices [online]. Available from URL: http://www.cdc.gov/h1n1flu/eua/ [Accessed 2010 Jul 26]
71. Centers for Disease Control and Prevention (CDC). Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season [online]. Available from URL: http://www.cdc.gov/h1n1flu/recommendations.htm [Accessed 2010 Jun 25]
72. Public Health Agency of Canada. Guidance for expanded use of oseltamivir (Tamiflu) in children under one year of age in the context of pandemic (H1N1) 2009 [online]. Available from URL: alert-alerte/h1n1/guidance-lignesdirectrices/ guidance-tamiflu-eng.php [Accessed 2010 Jun 25]
73. Acosta EP, Jester P, Gal P, et al. Oseltamivir dosing for influenza infection in premature neonates. J Infect Dis 2010; 202: 563-566
74. Williamson JC, Pegram PS. Respiratory distress associated with zanamivir. N Engl J Med 2000; 342: 661-662
75. Freund B, Gravenstein S, ElliotM, et al. Zanamivir: a review of clinical safety. Drug Saf 1999; 21: 267-281
76. Murphy KR, Eivindson A, Pauksens K, et al. Efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled, multicenter study. Clin Drug Invest 2000; 20: 337-349
77. Nicholson KG, Aoki FY, Osterhaus ADME, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomized controlled trial. Lancet 2000; 355: 1845-1850
78. Hama R. Fifty sudden deaths may be related to central suppression [letter]. BMJ 2007; 335: 59
79. Maxwell SRJ. Tamiflu and neuropsychiatric disturbance in adolescents. BMJ 2007; 334: 1232-1233
80. Toovey S, Rayner C, Prinssen E, et al. Assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: a comprehensive review. Drug Saf 2008; 31: 1097-1114
81. Blumentals WA, Song X. The safety of oseltamivir in patients with influenza: analysis of healthcare claims data from six influenza seasons. Med Gen Med 2007; 9: 23
82. Yorifuji T, Suzuki E, Tsuda T. Oseltamivir and abnormal behaviors: true or not? Epidemiology 2009; 20: 619-621
83. Hama R. Fatal neuropsychiatric adverse reactions to oseltamivir: case series and overview of causal relationships. Int J Risk Safety Med 2008; 20: 5-36
84. Jefferson T, Jones M, Doshi P, et al. Possible harms of oseltamivir: a call for urgent action. Lancet 2009; 374: 1312-1313
85. Okamoto S, Kamiya I, Kishida K, et al. Experience with oseltamivir for infants younger than 1 year old in Japan. Pediatr Infect Dis J 2005; 24 (6): 575-576
86. Kimberlin DW, Shalabi M, AbzugMJ, et al. Safety of oseltamivir compared with the adamantanes in children less than 12 months of age. Pediatr Infect Dis J 2010; 29: 195-198
87. Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008; 359: 1-10
88. McKimm-Breschkin J. Resistance of influenza viruses to neuraminidase inhibitors: a review. Antiviral Res 2000; 47 (1): 1-17
89. Moscona A. Medical management of influenza infection. Annu Rev Med 2008; 59: 397-413
90. Hatakeyama S, Sugaya N, Ito M, et al. Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. JAMA 2007; 297: 1435-1442
91. Sheu TG, Deyde VM, Okomo-Adhiambo M, et al. Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide in 2004-2008. Antimicrob Agents Chemother 2008; 53 (9): 3284-3292
92. Meijer A, Lackenby A, Hungnes O, et al. Oseltamivir-resistant influenza virus A (H1N1): Europe, 2007-08 season. Emerg Infect Dis 2009; 15: 552-560
93. World Health Organization. Influenza A virus resistance to oseltamivir and other antiviral medicines [online]. Available from URL: . who.int/csr/disease/influenza/2008-9nhemisummaryreport/en/ [Accessed 2010 Jun 27]
94. Gooskens J, Jonges M, Claas ECJ, et al. Morbidity and mortality associated with nosocomial transmission of oseltamivir-resistant influenza A(H1N1) virus. JAMA 2009; 301: 1042-1046
95. Kiso M, Mitamura K, Sakai-Tagawa Y, et al. Resistant influenza viruses in children treated with oseltamivir: descriptive study. Lancet 2004; 364: 759-765
96. Oo C, Barrett J, Hill G, et al. Pharmacokinetics and dosage recommendations for oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs 2001; 3: 229-236
97. Govorkova EA, Fang H, TamM, et al. Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob Agents Chemother 2004; 48: 4855-4863
98. Ilyushina NA, Bovin NV, Webster RG, et al. Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 2006; 70: 121-131
99. Ison MG, Gnann JW, Nagy-Agren S, et al. Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza. Antivir Ther 2003; 8: 183-190
100. Calfee DP, Peng AW, Cass LM, et al. Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection. Antimicrob Agents Chemother 1999; 43: 1616-1620
101. Bantia S, Arnold CS, Parker CD, et al. Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Res 2006; 69: 39-45
102. Kohno S, Kida H, Mizuguchi M, et al. A double-blind, placebo controlled study of intravenous peramivir in acute influenza patients [abstract no. 302(V)]. Program and abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Disease Society of America 46th Annual Meeting; 2008 Oct 25-28; Washington, DC, 328
103. Hayden F. Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis 2009; 48: S3-13
104. Malakhov MP, Aschenbrenner LM, Smee DF, et al. Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 2006; 40: 1470-1479
105. Belser JA, Lu X, Szretter KJ, et al. DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. J Infect Dis 2007; 196: 1493-1499
106. Smee DF, Bailey KW, Wong MH, et al. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res 2008; 80 (3): 266-271
107. O Keefe BR, Smee DF, Turpin JA, et al. Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. Antimicrob Agents Chemother 2003; 47: 2518-2525
108. Sidwell RW, Barnard DL, Day CW, et al. Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother 2007; 31: 1285-1287
109. Beigel J, Bray M. Current and future antiviral therapy of severe seasonal andavian influenza. Antiviral Res 2008; 78: 91-102
110. Knight V, Gilbert BE. Ribavirin aerosol treatment of influenza. Infect DisClin North Am 1987; 1: 441-457
111. Hayden FG, Sable CA, Connor JD, et al. Intravenous ribavirin by constant infusion for serious influenza and parainfluenza virus infection. Antivir Ther 1996; 1: 51-56
112. Sidwell RW, Bailey KW, WongMH, et al. In vitro and in vivo influenza virusinhibitory effects of viramidine. Antivir Res 2005; 68: 10-17
113. Tompkins SM, Lo CY, Tumpey TM, et al. Protection against lethal influenza virus challenge byRNA interference in vivo. Proc Natl Acad SciUS A 2004; 101: 8682-8686
114. Ge Q, Filip L, Bai A, et al. Inhibition of influenza virus production in virusinfected mice by RNA interference. Proc Natl Acad Sci U S A 2004; 101: 8676-8681
115. Lu J, Guo Z, PanX, et al. Passive immunotherapy for influenzaAH5N1 virus infection with equine hyperimmune globulin F(ab)2 in mice. Respir Res2006; 7: 43
116. Zhou H, Jin M, Yu Z, et al. Effective small interfering RNAs targeting matrixand nucleocapsid protein gene inhibit influenza A virus replication in cells and mice. Antivir Res 2007; 76: 186-193
117. Zhou B, ZhongN, GuanY. Treatment with convalescent plasma for influenzaA (H5N1) infection. N Engl J Med 2007; 357: 1450-1451
118. Mancuso E, Gabay MP, Steinke LM, et al. Peramivir: an intravenousneuraminidase inhibitor for the treatment of 2009 H1N1 influenza. Ann Pharmacother 2010; 44 (7-8): 1240-1249
119. Centers for Disease Control and Prevention (CDC). Emergency use authorization of peramivir IVfact sheet for health care providers [online]. Available from URL: http://www.cdc.gov/h1n1flu/eua/ Final%20HCP%20Fact%20sheet%20Peramivir%20IVintravenous&ref;CDC.pdf [Accessed 2010 Jun 25]
120. Guar AH, Bagga B, Barman S, et al. Intravenous zanamivir for oseltamivirresistant 2009 H1N1 influenza. N Engl J Med 2010; 362 (1): 88-89
121. Dulek DE, Williams JV, Creech CB, et al. Use of intravenous zanamivir after development of oseltamivir resistance in a critically ill immunosuppressed child infected with 2009 pandemic influenza A (H1N1) virus. Clin Infect Dis 2010; 50 (11): 1493-1496
122. Calfee DP, Peng AW, Cass LM, et al. Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection. Antimicrob Agents Chemother 1999; 43: 1616-1620
123. Macdonald SJF, Watson KG, Cameron R, et al. Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are effective at onceweekly dosing regimen. Antimicrob Agents Chemother 2004; 48: 4542-4549
124. Heikkinen T, Silvennoinen H, Peltola V, et al. Burden of influenza in children in the community. J Infect Dis 2004; 190 (8): 1369-1373
125. Sullivan KM. Health impact of influenza in the United States. Pharmacoeconomics 1996; 9 Suppl. 3: 26-33
126. Gums JG, Pelletier EM, Blumentals WA. Oseltamivir and influenza-related complications, hospitalization and healthcare expenditure in healthy adults and children. Expert Opin Pharmacother 2008; 9 (2): 1-11
127. Townsend KA, Eiland LS. Combating influenza with antiviral therapy in the pediatric population. Pharmacotherapy 2006; 26 (1): 95-103
128. Shehab N, Patel PR, Srinivasan A, et al. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis 2008; 47: 735-743
129. Meier CR, Napalkov PN, Wegmüller Y, et al. Population-based study on incidence, risk factors, clinical complications, and drug utilization associated with influenza in the United Kingdom. Eur J Clin Microbiol InfectDis 2000; 19: 834-842
130. Neuzil KM, Mellen BG, Wright PF, et al. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342: 225-231
131. Ochoa C, Eiros JM, Inglada L, et al. Assessment of antibiotic prescription in acute respiratory infections in adults. J Infect 2000; 41: 73-83
132. Jefferson T, Demicheli V, Rivetti D, et al. Antivirals for influenza in healthy adults: systematic review. Lancet 2006; 367: 303-313
133. Kaiser L, Wat C, Mills T, et al. Impact of oseltamivir treatment on influenzarelated lower respiratory tract complications and hospitalizations. Arch Intern Med 2003; 163: 1667-1672
134. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. Lancet 1998; 352: 1877-1881
135. Shun-Shin M, ThompsonM,Heneghan C, et al.Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomized controlled trials. BMJ 2009; 339: b3172