Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013-14

Background: Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives: To describe the spectrum and clinical impact of co-infections. Study design: Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results: Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23-0.73], p = 0.003), leukocytosis (>11 K/μl, OR 3.7 [2.2-6.2], p < 0.001; reference: normal WBC 3.5-11 K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0-1.2], p = 0.001). Bacterial co-infections (OR 2.2 [1.4-3.6], p = 0.001) and viral co-infections (OR 3.1 [1.3-7.4], p = 0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p < 0.05) in bivariable analysis. Conclusions: Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.