Not all patients in whom infection with the H1N1 influenza virus is suspected or confirmed need to be treated. Many patients with mild disease can forgo pharmacotherapy. In fact, in many cases, it may even be prudent to discourage such patients from coming into their health care provider's office, in the interest of infection control. However, all patients with severe disease and those considered at high risk for complications from seasonal influenza should be offered therapy with antiviral agents.
Specific recommendations for therapy and infection control are summarized here. Clinicians are also advised to consult the CDC Web site (http://www.cdc.gov/h1n1flu/clinicians/), since the guidance is continuously updated. The World Health Organization (WHO) has also recently provided guidance for clinicians on the pharmacotherapy of the H1N1 virus and other influenza viruses. This is available on the WHO Web site.1
Nonspecific supportive measures include attention to hydration, use of cough medications, use of non-aspirin–containing analgesics, management of concurrent medical problems, and encouragement to avoid smoking and secondhand smoke, if possible. These measures are recommended for all patients with confirmed, probable, or suspected H1N1 influenza. More information on caring for ill persons and controlling the spread of infection in a home setting is available at http://www.cdc.gov/h1n1flu/guidance_homecare.htm.
Who should be treated? Anti-viral treatment is currently recommended for all hospitalized patients and in patients considered at high risk for complications (Table 1). For patients in these categories, clinicians are strongly advised to urgently institute antiviral therapy for H1N1 influenza without waiting for test results. Conversely, clinicians are advised to consider refraining from using antiviral therapy in other patients who present with mild disease and can either self-monitor their status or be followed up on an outpatient basis during their illness. Indiscriminate use of antivirals for influenza—either when influenza is not high in the differential diagnosis or when there is no clear indication for treatment—may lead to drug resistance. Such practice patterns could result tragically in the compromise of supplies of antiviral drugs, thereby making them unavailable for others in need of treatment. This has already occurred in communities where some persons hoarded supplies for presumed later use.
Which drugs to use. Two classes of drugs are used for anti-influenza therapy; each of these consists of 2 commonly used agents. The neuraminidase inhibitors (NAIs) include oseltamivir (Tamiflu) and zanamivir (Relenza). The NAIs are the mainstay of therapy for currently circulating pandemic novel H1N1 viral infection. Because oseltamivir is administered orally, it is easier to take than zanamivir, which is inhaled. Thus, of these 2 drugs, oseltamivir is the preferred agent. The other classes of drugs, the adamantanes (ADs), or M2 ion channel blockers, include amantadine (Symmetrel) and rimantadine (Flumadine).
Common adverse effects of drugs in the NAI class include nausea and vomiting for oseltamivir (because of the higher systemic levels associated with this agent) and bronchospasm for zanamivir (because it is inhaled; inhalation results in lower systemic levels). With drugs in the AD class, GI and CNS adverse effects are most common. Infectious Diseases Society of America has published seasonal influenza treatment guidelines that contain detailed information on these agents. These guidelines are available at http://www.journals.uchicago.edu/doi/full/10.1086/598513.
The problem of drug resistance. Resistance to antiviral drugs is a relatively recent phenomenon, and the reasons for its propagation are not well understood. Examples of such resistance include the resistance of H3N2 strains to the AD class of drugs and the resistance of the 2008-2009 seasonal influenza H1N1 virus (not the novel pandemic strain) to oseltamivir (but not zanamivir).
The novel H1N1 virus is now sensitive to both agents in the NAI class but resistant to those in the AD class. There have been only a few cases worldwide of patients infected with an oseltamivir-resistant novel H1N1 strain; no infections were observed among contacts of the patients infected with this drug-resistant strain.2 This resistance has been associated with an H275Y mutation in the neuraminidase gene.3 In those communities where a pattern of oseltamivir resistance in the seasonal H1N1 virus has been established, it is recommended that patients infected with the outbreak H1N1 viral strain receive zanamivir instead. If a patient in this situation cannot tolerate zanamivir, clinicians have been encouraged to add one of the two AD agents to oseltamivir as empiric treatment.4
1. World Health Organization. WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza and other influenza viruses. August 20, 2009. http://www.who.int/csr/resources/publications/swineflu/h1n1_use_antivirals_20090820/en/index.html. Accessed September 9, 2009.
2. Centers for Disease Control and Prevention. Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients—Seattle, Washington, 2009. MMWR. 2009;58:893-896. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0814a1.htm. Accessed August 26, 2009.
3. World Health Organization. Pandemic (H1N1) 2009—update 60. Laboratory-confirmed cases of pandemic (H1N1) 2009 as officially reported to WHO by States Parties to the IHR (2005) as 31 July 2009. http://www.who.int/csr/don/2009_08_04/en/index.html. Accessed August 26, 2009.
4. Centers for Disease Control and Prevention. Interim guidance on antiviral recommendations for patients with novel influenza A (H1N1) virus infection and their close contacts. http://www.cdc.gov/h1n1flu/recommendations.htm. Accessed May 24, 2009.
5. McGreer AJ. Diagnostic testing or empirica therapy for patients hospitalized with suspected influenza: what to do? Clin Infect Dis. 2009;48(suppl 1):S14-S19.
6. McGreer AJ, Green KA, Plevneshi A, et al; for the Toronto Invasive Bacterial Diseases Network. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis. 2007;45:1568-1575.
7. Centers for Disease Control and Prevention. Questions & Answers—2009 H1N1 flu (swine flu) and you. August 5, 2009. http://www.cdc.gov/h1n1flu/qa.htm. Accessed September 9, 2009.
8. Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008;57(RR-7):1Ð60.
9. Centers for Disease Control and Prevention. Interim guidance for clinicians on the prevention and treatment of novel influenza A (H1N1) influenza virus infection in infants and children. May 13, 2009. http://www.cdc.gov/h1n1flu/childrentreatment.htm. Accessed September 12, 2009.
10. Centers for Disease Control and Prevention. Interim guidance on antiviral recommendations for patients with novel influenza A(H1N1) virus infection and their close contacts. May 6, 2009. http://cdc.gov/h1n1flu/recommendations.htm. Accessed September 6, 2009.
11. Centers for Disease Control and Prevention. Use of influenza A (H1N1) 2009 monovalent vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR. 2009;59(RR-10):1-8. http://cdc.gov/mmwr/preview/mmwrhtml/rr58e0821a1.htm. Accessed September 9, 2009.
12. Schnirring L. Officials lower expectations for size of first novel flu vaccine deliveries. Centers for Infectious Disease Research and Policy (CIDRAP) News. http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/aug1409vaccine.html.
Accessed August 26, 2009.
13. Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR. 2009;58(RR-8):1-52. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5808a1.htm. Accessed September 9, 2009.
14. Centers for Disease Control and Prevention. H1N1 Flu Vaccination Resources. http://www.cdc.gov/h1n1flu/vaccination. Accessed August 26, 2009.
15. Centers for Disease Control and Prevention. Interim guidance for use of 23-valent pneumococcal polysaccharide vaccine during novel influenza A (H1N1) outbreak. http://www.cdc.gov/h1n1flu/guidance/ppsv_h1n1.htm. Accessed August 26, 2009.
16. Centers for Disease Control and Prevention. Novel influenza A (H1N1) virus infections in three pregnant women—United States, April-May 2009. MMWR. 2009;58:497-500. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0512a1.htm. Accessed August 26, 2009.
17. Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1003-1032. http://journals.uchicago.edu/doi/full/10.1086/598513. Accessed August 26, 2009.