Abstract
Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety.
Highlights
The influenza A(H1N1)pdm09 [pH1N1] virus emerged in April 2009 to cause a global pandemic [1,2,3]
A case was defined as a California resident who was hospitalized in an intensive care unit (ICU) for $24 hours with signs and symptoms consistent with acute respiratory infection and laboratory evidence of pH1N1 virus infection by reverse-transcription polymerase chain reaction (RT-PCR)
Fifty-two of these cases received oseltamivir as a second antiviral, and another five cases were treated with peramivir plus two or more other antivirals [e.g. oseltamivir and amantadine (1), oseltamivir and inhaled zanamivir (1), oseltamivir and rimantadine (2), and amantadine and ribavirin (1)]
Summary
The influenza A(H1N1)pdm09 [pH1N1] virus emerged in April 2009 to cause a global pandemic [1,2,3]. The only available antiviral drugs for treatment of pH1N1 were the neuraminidase inhibitors (NAI), oral oseltamivir or inhaled zanamivir. Administration of entericallyadministered oseltamivir can be challenging in the ICU where patients may have difficulty tolerating oral administration of capsules or intestinal ileus may cause malabsorption [4]. Under the EUA, peramivir was distributed by the Centers for Disease Control and Prevention (CDC) for treatment of hospitalized pediatric and adult patients with evidence of pH1N1 virus infection and who 1) were not responding to antiviral therapy, or 2) the clinician deemed that enteral or inhaled delivery of NAIs was not dependable or feasible [5]
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