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

Nirav S Shah, Jared A Greenberg, Moira C McNulty, Kevin S Gregg, James Riddell 4th, Julie E Mangino, Devin M Weber, Courtney L Hebert, Natalie S Marzec, Michelle A Barron, Fredy Chaparro-Rojas, Alejandro Restrepo, Vagish Hemmige, Kunatum Prasidthrathsint, Sandra Cobb, Loreen Herwaldt, Vanessa Raabe, Christopher R Cannavino, Andrea Green Hines, Sara H Bares, Philip B Antiporta, Tonya Scardina, Ursula Patel, Gail Reid, Parvin Mohazabnia, Suresh Kachhdiya, Binh-Minh Le, Connie J Park, Belinda Ostrowsky, Ari Robicsek, Becky A Smith, Jeanmarie Schied, Micah M Bhatti, Stockton Mayer, Monica Sikka, Ivette Murphy-Aguilu, Priti Patwari, Shira R Abeles, Francesca J Torriani, Zainab Abbas, Sophie Toya, Katherine Doktor, Anindita Chakrabarti, Susanne Doblecki-Lewis, David J Looney, Michael Z David, Nirav S Shah, Jared A Greenberg, Moira C McNulty, Kevin S Gregg, James Riddell 4th, Julie E Mangino, Devin M Weber, Courtney L Hebert, Natalie S Marzec, Michelle A Barron, Fredy Chaparro-Rojas, Alejandro Restrepo, Vagish Hemmige, Kunatum Prasidthrathsint, Sandra Cobb, Loreen Herwaldt, Vanessa Raabe, Christopher R Cannavino, Andrea Green Hines, Sara H Bares, Philip B Antiporta, Tonya Scardina, Ursula Patel, Gail Reid, Parvin Mohazabnia, Suresh Kachhdiya, Binh-Minh Le, Connie J Park, Belinda Ostrowsky, Ari Robicsek, Becky A Smith, Jeanmarie Schied, Micah M Bhatti, Stockton Mayer, Monica Sikka, Ivette Murphy-Aguilu, Priti Patwari, Shira R Abeles, Francesca J Torriani, Zainab Abbas, Sophie Toya, Katherine Doktor, Anindita Chakrabarti, Susanne Doblecki-Lewis, David J Looney, Michael Z David

Abstract

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 (>11K/μl, OR 3.7 [2.2-6.2], p<0.001; reference: normal WBC 3.5-11K/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.

Keywords: Co-infection; ICU; Influenza A (H1N1) pdm09; MRSA; Severe influenza; Staphylococcus aureus.

Copyright © 2016 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Antibiogram of Staphylococcus aureus isolates (n = 47) from co-infections, showing the percent that were resistant or intermediate to selected antibacterial drugs from 47 patients with severe influenza in the U.S. between September 1, 2013 and April 1, 2014.
Fig. 2
Fig. 2
Percentage of community-acquired and hospital-acquired co-infections attributed to Staphylococcus aureus, Enterobacteriaceae and Pseudomonas sp. among 507 patients with severe influenza in the U.S. between September 1, 2013 and April 1, 2014.

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