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

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.

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.