Lessons from the 2009 Pandemic Flu Experience
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Hospital Epidemiologist, Sequoia Hospital, Redwood City, CA, is Editor for Infectious Disease Alert.
Synopsis: Hospitalized patients infected with the 2009 pandemic influenza virus who developed pneumonia frequently required intensive care, mechanical ventilation, and many died.
Source: Jain S, et al; for the 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team. Influenza-associated pneumonia among hospitalized patients with 2009 pandemic influenza A (H1N1) Virus — United States, 2009. Clin Infect Dis 2012; 54:1221-1229.
Jain and colleagues at the U.S. CDC evaluated the characteristics of 195 hospitalized patients with laboratory-confirmed influenza influenza A pdm09 (pH1N1) infection who had pneumonia, comparing them to hospitalized flu patients without pneumonia. Those with pneumonia were more likely to have been ill for >2 days prior to hospitalization and to have a preexisting neurological condition, but less likely to have other underlying medical conditions, including asthma or chronic obstructive lung disease.
Admission white blood cell counts were normal in one-half of those with pneumonia while leukopenia and leukocytosis were each present in one-fourth. Bacterial infection was diagnosed in 3 patients without and 13 patients with pneumonia (including 7 patients with positive blood cultures - 5 with Staphylococus aureus). Two of the 3 bacteria-infected patients without pneumonia were bacteremic, both with S. aureus. Approximately four-fifths of patients with and without pneumonia received antiviral therapy, most often (91%) oseltamivir, but those with pneumonia were less likely to have received antiviral therapy within 48 hours of illness onset. Patients with pneumonia were significantly more likely than patients without pneumonia to receive antibiotics (93% vs. 67%). Approximately one-half of pneumonia patients were admitted to an intensive care unit compared to one-sixth of those without evident lower respiratory tract infection. Mechanical ventilation was required in 39% of pneumonia patients; 34 (17%) of the patients with pneumonia died.
The pH1N1 virus was resistant to amantadine and rimantidine, leaving orally administered oseltamivir and inhaled zanamivir (neither of which had received FDA approval for complicated infection) as the only readily available therapeutic options. The lack of a commercially available drug that could be parenterally administered was believed to be problematic for at least some critically ill patients. Two investigational products became available — peramivir, which was provided under an Emergency Use Authorization (EUA) through the CDC, and a formulation of zanamivir (which maintains activity against viruses containing the H275Y mutation) — each suitable for intravenous administration associated with oseltamivir resistance.
The EUA required that all medication errors, selected adverse events (AE), serious adverse events, and deaths occurring during peramivir therapy be reported to the FDA within 7 calendar days. Sorbello and colleagues reviewed reports on 344 patients of the "at least" 1274 who were provided peramivir.1,2 The most frequently reported serious AEs were death (15%), H1N1 influenza (8%), respiratory failure (8%), acute renal failure (7%), and acute respiratory distress syndrome (7%). Skin rash was the only AE attributed to peramivir.
No assessment of the efficacy of peramivir could be made — a critical shortcoming of the emergency system (one of many). As pointed out in an accompanying editorial by Andrew Pavia, it is essential that better planning for data collection in similar situations be put in place before the event.3 This, together with the development of a funded national collaborative clinical trials system, would go a long way toward resolving some of the collosal shortcomings in accurate therapeutic data in the field of infectious diseases.
- Yu Y, et al. Peramivir Use for Treatment of Hospitalized Patients With Influenza A(H1N1)pdm09 Under Emergency Use Authorization, October 2009-June 2010. Clin Infect Dis 2012;May 4.[Epub ahead of print] PubMed PMID: 22491506.
- Sorbello A, et al. Emergency Use Authorization for Intravenous Peramivir: Evaluation of Safety in the Treatment of Hospitalized Patients Infected With 2009 H1N1 Influenza A Virus. Clin Infect Dis 2012 May 4. [Epub ahead of print] PubMed PMID: 22491501.
- Pavia AT. What Did We Learn From the Emergency Use Authorization of Peramivir in 2009? Clin Infect Dis 2012 May 4. [Epub ahead of print] PubMed PMID: 22491500.