The basis for recommending antiviral therapy of patients hospitalized with influenza is derived from multiple observational studies which have demonstrated a clinical benefit in treatment of this population, including reduced mortality. This benefit has been documented for seasonal and pandemic influenza, and in ICU as well as non-ICU patients. Our data did not demonstrate an association between antiviral therapy and reduced risk of in hospital risk adjusted mortality in the pandemic and two subsequent influenza seasons; however the numbers of deaths in the three seasons, and numbers of patients who died who had not been treated with antiviral therapy were quite low (123 and 25 respectively).
While there is strong evidence for better clinical efficacy if antiviral therapy is initiated early, there is some evidence for clinical efficacy even when treatment is delayed up to 5 days following onset of illness; on theoretical grounds treatment may be effective in some subgroups when started even later . Based on these data , the Infectious Diseases Society of America (IDSA), and its Canadian counterpart, the Association for Medical Microbiology and Infectious Diseases - Canada strongly recommend the use of antiviral therapy in all patients unwell enough to be hospitalized when treatment can be started early in the course of the illness, and recommend it when the diagnosis is made late in the course [6, 7].
In our hospital network, as in US hospitals, the proportion of cases admitted to hospital that were treated with antiviral agents greatly increased during the 2009 pandemic year. It is therefore disconcerting to find that the gains in treatment have been substantially lost in the post pandemic period. Garg et al. demonstrated a 6% decline in antiviral therapy of adults admitted to US hospitals from 82% during the pandemic, to 77% in the first post pandemic year . Our data illustrates a more precipitate and progressive trend in patients hospitalized in Canadian hospitals, from the peak of 89.6% during the pandemic to only 65.7% in the second post pandemic year. This trend was widespread affecting all age groups, including the elderly, and all underlying co-morbid conditions. Furthermore it was also experienced by patients sick enough to require ICU admission.
Given the consensus that hospitalized patients should be treated, reasons for the declining use of antiviral therapy are not clear. The decline in enthusiasm for treatment may in part be driven by controversy around efficacy of antiviral therapy based on clinical trials data. Randomized trials of antiviral therapy, primarily oseltamivir, have undergone recent re-examination raising doubt regarding the clinical benefit of treatment . However, these trials are not directly relevant to hospitalized patients, since they were conducted largely on otherwise healthy ambulatory patients.
The very high proportion of use of antivirals in 2009 occurred in the context of a pandemic and represented a marked increased compared with previous seasons. The subsequent decrease may represent a gradual return to the pre-pandemic healthcare worker behavior, or a perception that seasonal influenza, even in hospitalized patients, may be of lesser severity. This suggests that the effect of the intensive training and promotion that were conducted in the context of the pandemic was short-lived.