Research Article: Antiviral Treatment among Older Adults Hospitalized with Influenza, 2006-2012

Date Published: March 25, 2015

Publisher: Public Library of Science

Author(s): Mary Louise Lindegren, Marie R. Griffin, John V. Williams, Kathryn M. Edwards, Yuwei Zhu, Ed Mitchel, Alicia M. Fry, William Schaffner, H. Keipp Talbot, Krzysztof Pyrc.


To describe antiviral use among older, hospitalized adults during six influenza seasons (2006—2012) in Davidson County, Tennessee, USA.

Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals.

We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753) of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001). There were 125 (7.1%) patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046) during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35) and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71) were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use. In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.

Partial Text

Influenza is estimated to cause an average of 200,000 hospitalizations and 3,300 to 49,000 deaths each year in the US.[1–4] Since the 2009–2010 H1N1 influenza pandemic, the Centers for Disease Control and Prevention (CDC) has recommended prompt use of antiviral treatment for all hospitalized patients with confirmed or suspected influenza. [5, 6] Use of antiviral treatment among hospitalized patients has been associated with reduced mortality, with earlier treatment resulting in better outcomes. [6–8] Despite these recommendations, barriers to prompt antiviral treatment among hospitalized patients include lack of reliable rapid influenza diagnostic tests, late presentation of patients to care, difficulty distinguishing influenza clinically from other acute respiratory infections and a lack of confidence in the effectiveness of antivirals.[9–11] Additionally, influenza often manifests atypically in adults ≥50 [12, 13], presenting as exacerbations of underlying conditions such as asthma or chronic obstructive pulmonary disease (COPD). Few data are available on trends in the use of antiviral therapy among high-risk, hospitalized, older adult populations.

Over six influenza seasons (2006–2012) in urban Tennessee, use of antiviral treatment was low among hospitalized patients ≥50 years recognized to have influenza by their provider and those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza and changed little over time. Clinical testing for influenza remained infrequent and consisted primarily of rapid antigen tests, which have a low sensitivity in our study population (25%)[20]. Nevertheless, confirmed influenza by clinical laboratory testing was a predictor of antiviral treatment. Research laboratory testing (not available to the clinicians) was also a predictor of treatment and identified many more patients with influenza who could have benefited from treatment with antivirals. Persons who were treated in the absence of a positive clinical test were much more likely to be influenza positive by research testing than untreated patients, indicating that for a small subset of subjects, clinicians correctly identified those likely to have influenza. Those subjects who had no clinical laboratory testing performed, the population eligible for empiric treatment, were less likely to receive antivirals than those with negative test results, suggesting that providers tested those patients with a perceived higher likelihood of having influenza. However, despite positive clinical testing associated with receipt of antivirals, the number of subjects receiving antivirals still remained low. Strikingly, receipt of antivirals was not independently associated with severity of illness, duration of symptoms, underlying high-risk conditions, influenza season, or age.

Despite recommendations for early, universal use of antivirals for all hospitalized patients with confirmed or suspected influenza since the H1N1 pandemic (2009–2010) antiviral use was low. Although there was a moderate increase in influenza testing since the pandemic, testing remained low and used mostly rapid antigen tests, which we and others have shown to be insensitive for detecting influenza in hospitalized adults ≥50 years. Antiviral treatment without a positive influenza test was rare. These results confirm that antivirals sometimes are not used because influenza is not clinically diagnosed, due to the poor sensitivity of the rapid influenza tests. More accurate point of care influenza tests could facilitate receipt of antivirals among hospitalized patients. Because treatment of hospitalized patients with antivirals is associated with reductions in morbidity or mortality, CDC and IDSA guidelines recommend use of antivirals for all hospitalized patients with confirmed or suspected influenza. Additional strategies are needed to improve appropriate antiviral treatment among hospitalized adults with influenza, particularly for older adults with severe disease or with underlying high-risk conditions.