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Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States*

Rice, Todd W. MD, MSc; Rubinson, Lewis MD, PhD; Uyeki, Timothy M. MD, MPH, MPP; Vaughn, Frances L. PhD; John, Benjamin B. PhD, MS, MSc; Miller, Russell R. III MD, MPH; Higgs, Elizabeth MD, MIA, DTMH; Randolph, Adrienne G. MD, MSc; Smoot, B. Elizabeth MS; Thompson, B. Taylor MD; for the NHLBI ARDS Network

doi: 10.1097/CCM.0b013e3182416f23
Clinical Investigations

Objectives: The contribution of bacterial coinfection to critical illness associated with 2009 influenza A virus infection remains uncertain. The objective of this study was to determine whether bacterial coinfection increased the morbidity and mortality of 2009 influenza A.

Design: Retrospective and prospective cohort study.

Setting: Thirty-five adult U.S. intensive care units over the course of 1 yr.

Patients: Six hundred eighty-three critically ill adults with confirmed or probable 2009 influenza A.

Interventions: None.

Measurements and Main Results: A confirmed or probable case was defined as a positive 2009 influenza A test result or positive test for influenza A that was otherwise not subtyped. Bacterial coinfection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hrs of intensive care unit admission. The mean age was 45 ± 16 yrs, mean body mass index was 32.5 ± 11.1 kg/m2, and mean Acute Physiology and Chronic Health Examination II score was 21 ± 9, with 76% having at least one comorbidity. Of 207 (30.3%) patients with bacterial coinfection on intensive care unit admission, 154 had positive cultures with Staphylococcus aureus (n = 57) and Streptococcus pneumoniae (n = 19), the most commonly identified pathogens. Bacterial coinfected patients were more likely to present with shock (21% vs. 10%; p = .0001), require mechanical ventilation at the time of intensive care unit admission (63% vs. 52%; p = .005), and have longer duration of intensive care unit care (median, 7 vs. 6 days; p = .05). Hospital mortality was 23%; 31% in bacterial coinfected patients and 21% in patients without coinfection (p = .002). Immunosuppression (relative risk 1.57; 95% confidence interval 1.20 –2.06; p = .0009) and Staphylococcus aureus at admission (relative risk 2.82; 95% confidence interval 1.76–4.51; p < .0001) were independently associated with increased mortality.

Conclusions: Among intensive care unit patients with 2009 influenza A, bacterial coinfection diagnosed within 72 hrs of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality.

From the Vanderbilt University School of Medicine (TWR), Nashville, TN; National Disaster Medical System (LR), HHS/ASPR/OPEO; National Center for Immunization and Respiratory Diseases (TMU), Centers for Disease Control and Prevention; Emergency Care Coordination Center (FLV, BBJ), HHS/ASPR/OPEO; Intermountain Medical Center and University of Utah School of Medicine (RRM), Salt Lake City, UT; Division of Clinical Research (EH), National Institutes of Allergy and Infectious Diseases, NIH; Children’s Hospital Boston (AGR), Boston, MA; Harvard Medical School (BES), Boston, MA; Massachusetts General Hospital (BTT), Harvard Medical School, Boston, MA.

*See also p. 1664.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (http://journals.lww.com/ccmjournal).

Supported, in part, by NHLBI N01-HR-56179.

The authors have not disclosed any potential conflicts of interest.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

For information regarding this article, E-mail: todd.rice@vanderbilt.edu

Network Participants: University of Washington, Harborview: Hudson†, C. Hough, M. Neff, K. Sims, A. Ungar; Baystate Medical Center: J. Steingrub†, E. Braden, L. DeSouza, J. Germain, M. Tidswell, C. Kardos, D. Kelley, L. Kozikowski, S. Ouellette; Baylor College of Medicine: K. Guntupalli, V. Bandi, C. Pope, C. Ross; Johns Hopkins University: R. Brower†, P. Mendez-Tellez, K. Oakjones, J. Sevransky, A. Workneh; University of Maryland: C. Shanholtz, A. Holmatova, G. Netzer, P. Rock, A. Sampaio, J. Titus; Union Memorial Hospital: P. Sloane, T. Beck, H. Highfield; Washington Hospital Center: B. Lee, N. Bolouri; Cleveland Clinic Foundation: H.P. Wiedemann†, R. Ashton, D. Culver, T. Frederick, J. Komara, J. Guzman, A. Reddy; University Hospitals of Cleveland: R. Hejal, M. Andrews, D. Haney; MetroHealth Medical Center: A.F. Connors, S. Lasalvia, J. D. Thornton, E.L. Warren; University of Colorado Health Science Centers: M. Moss†, M. Mealer; Denver Health Medical Center: I. Douglas, K. Overdier, K. Thompson, R. Wolken; Duke University: N. MacIntyre†, L. Brown, C. Cox, J. Govert, N. Knudsen; University of North Carolina: S. Carson, S.Choudhury, W. Hall, J. Lanier; Vanderbilt University: A. P. Wheeler†, G.R. Bernard, M. Hays, S. Mogan, T. W. Rice; Wake Forest University: R.D. Hite†, Mary Ragusky; Moses Cone Memorial Hospital: P. Wright, S. Gross, J. McLean, A. Overton; University of Virginia: J. Truwit, K. Enfield, M. Marshall; LDS Hospital and Intermountain Medical Center: A. Morris†, A. Austin, S. Brown T. Clemmer, H. Gallo, T. Graydon, C. Grissom, E. Hirshberg, N. Kumar, R. Miller, D. Murphy, J. Orme, L. Struck, L. Weaver; McKay-Dee Hospital: C. Lawton, D. Hanselman; Utah Valley Regional Medical Center: K. Sundar, D. Eckley, K. Ludwig, D. Nielsen; University of California, San Francisco: M.A. Matthay†, C. Calfee, B. Daniel, M. Eisner, O. Garcia, K. Kordesch, K. Liu, H. Zhou; University of California, San Francisco, Fresno: M. W. Peterson, J. Blaauw; University of California-Davis: T. Albertson, E. Vlastelin; Mayo Foundation: R. Hubmayr†, D. Brown, M. Dubin, E. Festic, R. Hinds, S. Holets, A. Lee, M. Passe, J. Wright; Louisiana State University: B. deBoisblanc†, P. Lauto, C. Romaine; Louisiana State University: Earl K. Long; Baton Rouge General Medical Center Mid-City and Baton Rouge General Medical Center, Bluebonnet: S. Brierre, C. LeBlanc; Alton-Ochsner Clinic Foundation: D. Taylor; Clinical Coordinating Center (Massachusetts General Hospital and Harvard Medical School): D. Schoenfeld†, M. Guha, E. Hammond, N. Lavery, P. Lazar, R. Morse, C. Oldmixon, N. Ringwood, E. Smoot, B.T. Thompson; National Heart, Lung, and Blood Institute: A. Harabin, S. Bredow, M. Waclawiw, G. Weinmann.

†Principal Investigator.

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins