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Research Letters |

Use of Intravenous Neuraminidase Inhibitors During the 2009 Pandemic: Results From Population-Based Surveillance FREE

Alicia M. Fry, MD, MPH; Alejandro Pérez, MPH; Lyn Finelli, DPH
JAMA. 2011;306(2):160-162. doi:10.1001/jama.2011.950.
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Published online

To the Editor: During 2009, neuraminidase inhibitors (NAIs) were recommended for treatment of pandemic influenza A virus (pH1N1) infection1; oral oseltamivir and inhaled zanamivir are the only licensed NAIs in the United States. During the pandemic, 2 experimental intravenous (IV) NAIs, zanamivir and peramivir, were available by emergency investigational new drug or emergency use authorization request.2,3 We report the frequency and characteristics of patients who received an experimental IV NAI from a population-based, active surveillance of hospitalized patients.

We identified patients with laboratory-confirmed pH1N1 infection from the Emerging Infections Program Influenza-Associated Hospitalization Surveillance. The surveillance area includes 22 million adults and children from select counties in 10 states that represent approximately 7% of the US population.4,5 Hospitalization associated with pH1N1 was defined as laboratory-confirmed influenza (pH1N1 or influenza A unsubtyped) in a patient admitted to a hospital in the surveillance area between April 2009 and April 2010, a period when pH1N1 was the predominant circulating virus. Laboratory confirmation included a positive result within 14 days of admission from viral culture, direct or indirect fluorescent antibody staining, rapid antigen test, or polymerase chain reaction or documentation of a positive test result in a patient's medical record. Demographic and clinical data were collected from medical records, including antiviral agents but not adverse events. Protocols were approved by local and federal internal review boards, as necessary. The need for consent was waived. Comparison of patients who received only licensed NAIs with those who ever received an IV NAI was done by χ2 or Wilcoxon rank sum tests (SAS version 9.2; SAS Institute, Cary, North Carolina). A 2-sided P ≤ .05 was considered significant.

Of 7759 laboratory-confirmed pH1N1 hospitalizations identified, 6216 patients (80%) had documented receipt of an NAI; more than 99% received oseltamivir (Table). Among those who received an NAI, 0.2% of children and 1% of adults received an IV NAI; 33 received peramivir (1 child) and 8 received IV zanamivir (2 children). All received peramivir after the emergency use authorization.2 Patients receiving IV NAIs were less likely to have renal disease and more likely to have serious illness, be obese, and begin treatment with any NAI later compared with patients receiving licensed NAIs. Among 1417 patients with pH1N1 infection requiring intensive care unit admission, 1336 (94%) received only oseltamivir and began NAIs a median of 3 days (range, 0-33 days) after onset of illness; 3% received an IV NAI.

Table Graphic Jump LocationTable. Characteristics of Patients Hospitalized With Laboratory-Confirmed pH1N1 Infection Who Received US FDA Licensed and Experimental IV Neuraminidase Inhibitors: Emerging Infections Program Influenza-Associated Hospitalization Surveillance, April 2009-April 2010a

Most patients (88%) received oseltamivir prior to receiving an IV NAI, 1 started oseltamivir and peramivir simultaneously, 1 received peramivir as the first NAI, and 3 did not have dates recorded for antiviral use. Intravenous NAIs were initiated a median of 3 days (range, 0-12 days) after antiviral treatment was initiated; 16 of 38 patients (42%) with dates for antiviral use started IV NAIs within 2 days of treatment initiation. Ten patients received oseltamivir and IV NAI simultaneously for 2 or more days.

This summary of a nationally representative sample of hospitalized patients with laboratory-confirmed pH1N1 infection during the pandemic indicates that most hospitalized patients with pH1N1 infection received treatment with an NAI; however, receipt of an experimental IV NAI was rare. Limited data on effectiveness and safety in severely ill patients and children and on dosing for renal failure were available for the IV NAIs, which may have reduced use. The surveillance does not collect data to assess adverse events or the reasons for treatment and cannot evaluate the effectiveness of IV NAIs. Patients who received experimental IV NAIs tended to be more severely ill and obese; thus, an adequate comparison group was not available. Randomized controlled trials are best suited to evaluate the efficacy and adverse events of experimental drugs. Ongoing studies will inform appropriate use of new agents in the future.

Author Affiliations: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia (afry@cdc.gov).

Author Contributions: Dr Fry had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Fry, Finelli.

Acquisition of data: Pérez, Finelli.

Analysis and interpretation of data: Fry, Pérez, Finelli.

Drafting of the manuscript: Fry.

Critical revision of the manuscript for important intellectual content: Fry, Pérez, Finelli.

Statistical analysis: Pérez.

Administrative, technical, or material support: Finelli.

Study supervision: Fry, Finelli.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Disclaimer:The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Additional Contributions: We would like to acknowledge the following for their participation in the collection and management of Influenza-Associated Hospitalization Surveillance data: Art Reingold, MD, California Emerging Infections Program, Oakland; Ken Gershman, MD, Colorado Department of Public Health and Environment, Denver; Kimberly Yousey-Hindes, MPH, CPH, Connecticut Emerging Infections Program, Yale School of Public Health, New Haven; Kathryn Arnold, MD, Georgia Emerging Infections Program, Emory University School of Medicine, Atlanta; Patricia Ryan, MS, Maryland Department of Health and Mental Hygiene, Baltimore; Ruth Lynfield, MD, and Craig Morin, MPH, Minnesota Department of Health, St Paul; Joan Baumbach, MD, MPH, and Emily B. Hancock, MS, New Mexico Department of Health, Santa Fe; Nancy M. Bennett, MD, and Shelley Zansky, PhD, Emerging Infections Program, New York State Department of Health, Albany; Ann Thomas, MD, MPH, Oregon Public Health Division, Portland; William Schaffner, MD, and David Kirschke, MD, Tennessee Department of Health, Nashville; and Laurie Kamimoto, MD; Tiffany D’Mello, MPH; and Michael Jhung, MD, MPH, Influenza Division, Centers for Disease Control and Prevention, Atlanta. No one received compensation for the contributions beyond their salaries.

 Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. Centers for Disease Control and Prevention. http://www.cdc.gov/h1n1flu/recommendations.htm. Accessed January 31, 2010
Birnkrant D, Cox E. The Emergency Use Authorization of peramivir for treatment of 2009 H1N1 influenza.  N Engl J Med. 2009;361(23):2204-2207
PubMed   |  Link to Article
 Emergency use authorization of peramivir IV fact sheet for health care providers. Food and Drug Administration. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInormationforPatientsandProviders/UCM187811.pdf. Accessed January 6, 2011
Dawood F, Fiore A, Kamimoto L,  et al.  Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008.  J Pediatr. 2010;157(5):808-814
PubMed   |  Link to Article
Dao CN, Kamimoto L, Nowell M,  et al.  Adult hospitalizations for laboratory-positive influenza during the 2005-2006 through 2007-2009 seasons in the United States.  J Infect Dis. 2010;202(6):881-888
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Characteristics of Patients Hospitalized With Laboratory-Confirmed pH1N1 Infection Who Received US FDA Licensed and Experimental IV Neuraminidase Inhibitors: Emerging Infections Program Influenza-Associated Hospitalization Surveillance, April 2009-April 2010a

References

 Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. Centers for Disease Control and Prevention. http://www.cdc.gov/h1n1flu/recommendations.htm. Accessed January 31, 2010
Birnkrant D, Cox E. The Emergency Use Authorization of peramivir for treatment of 2009 H1N1 influenza.  N Engl J Med. 2009;361(23):2204-2207
PubMed   |  Link to Article
 Emergency use authorization of peramivir IV fact sheet for health care providers. Food and Drug Administration. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInormationforPatientsandProviders/UCM187811.pdf. Accessed January 6, 2011
Dawood F, Fiore A, Kamimoto L,  et al.  Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008.  J Pediatr. 2010;157(5):808-814
PubMed   |  Link to Article
Dao CN, Kamimoto L, Nowell M,  et al.  Adult hospitalizations for laboratory-positive influenza during the 2005-2006 through 2007-2009 seasons in the United States.  J Infect Dis. 2010;202(6):881-888
PubMed   |  Link to Article

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