Skip to main content Accessibility help
×
Home
Hostname: page-component-55597f9d44-zdfhw Total loading time: 0.248 Render date: 2022-08-14T13:34:30.544Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

Bacterial coinfection in influenza pneumonia: Rates, pathogens, and outcomes

Published online by Cambridge University Press:  23 April 2021

Patricia S. Bartley
Affiliation:
Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio
Abhishek Deshpande
Affiliation:
Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio
Pei-Chun Yu
Affiliation:
Department of Quantitative Health Sciences, Cleveland Clinic, Ohio
Michael Klompas
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
Sarah D. Haessler
Affiliation:
Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School–Baystate, Springfield, Massachusetts
Peter B. Imrey
Affiliation:
Department of Quantitative Health Sciences, Cleveland Clinic, Ohio Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
Marya D. Zilberberg
Affiliation:
EviMed Research Group, LLC, Goshen, Massachusetts
Michael B. Rothberg*
Affiliation:
Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio
*
Author for correspondence: Michael Rothberg, E-mail: rothbem@ccf.org

Abstract

Background:

Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.

Methods:

We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.

Results:

Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).

Conclusions:

In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Muir, R, Wilson, GH. Observations on influenza and its complications. Br Med J 1919;1:35.CrossRefGoogle ScholarPubMed
Chien, YW, Klugman, KP, Morens, DM. Bacterial pathogens and death during the 1918 influenza pandemic. N Engl J Med 2009;361:25822583.10.1056/NEJMc0908216CrossRefGoogle ScholarPubMed
Brundage, JF and Shanks, GD. Deaths from bacterial pneumonia during 1918–1919 influenza pandemic. Emerg Infect Dis 2008;14:11931199.CrossRefGoogle Scholar
Sheng, ZM, Chertow, DS, Ambroddio, X, et al. Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak. Proc Natl Acad Sci U S A 2011;108:1641616421.10.1073/pnas.1111179108CrossRefGoogle ScholarPubMed
Schwarzmann, SW, Adler, JL, Sullivan, RJ Jr, Marine, WM. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch Intern Med 1971;127:10371041.10.1001/archinte.1971.00310180053006CrossRefGoogle Scholar
MacIntyre, CR, Chughtai, AA, Barnes, M, et al. The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a (H1N1)pdm09. BMC Infect Dis 2018;18:637.CrossRefGoogle ScholarPubMed
Morens, DM, Taubenberger, JK, Fauci, AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008;198:962970.10.1086/591708CrossRefGoogle ScholarPubMed
Murray, RJ, Robinson, JO, White, JN, et al. Community-acquired pneumonia due to pandemic A (H1N1) 2009 influenzavirus and methicillin-resistant Staphylococcus aureus coinfection. PLoS One 2010;5:e8705.10.1371/journal.pone.0008705CrossRefGoogle Scholar
Lee, EH, Wu, C, Lee, EU, et al. Fatalities associated with the 2009 H1N1 influenza A virus in New York City. Clin Infect Dis 2010;50:14981504.CrossRefGoogle ScholarPubMed
Opatowski, L, Baguelin, M, Eggo, RM. Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: a key role for mathematical modelling. PLoS Pathog 2018;14:e1006770.CrossRefGoogle ScholarPubMed
Metersky, ML, Masterson, RG, Lode, H, File, TM Jr, Babinchak, T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis 2012;16:e321e331.CrossRefGoogle ScholarPubMed
Klein, EY, Monteforte, B, Gupta, A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses 2016;10:394403.10.1111/irv.12398CrossRefGoogle ScholarPubMed
Yang, M, Gao, H, Chen, J, et al. Bacterial coinfection is associated with severity of avian influenza A (H7N9), and procalcitonin is a useful marker for early diagnosis. Diagn Microbiol Infect Dis 2016;84:165169.CrossRefGoogle Scholar
Palacios, G, Hornig, M, Cisterna, D, et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS One 2009;4:e8540.10.1371/journal.pone.0008540CrossRefGoogle ScholarPubMed
Joseph, C, Togawa, Y, Shindo, N. Bacterial and viral infections associated with influenza. Influenza Other Respir Virus 2013;7:105113.CrossRefGoogle ScholarPubMed
Shrestha, S, Foxman, B, Weinberger, DM, Steiner, C, Viboud, C, Rohani, P. Identifying the interaction between influenza and pneumococcal pneumonia using incidence data. Sci Transl Med 2013;5:191ra84.10.1126/scitranslmed.3005982CrossRefGoogle ScholarPubMed
Scaber, J, Saeed, S, Ihekweazu, C, Efstratiou, A, McCarthy, N, O’Moore, E. Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in South East England. Euro Surveill 2011;16.Google ScholarPubMed
Chertow, DS, Memoli, MJ. Bacterial coinfection in influenza: a grand rounds review. JAMA 2013;309:275282.10.1001/jama.2012.194139CrossRefGoogle ScholarPubMed
Brundage, JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis 2006;6:303312.CrossRefGoogle ScholarPubMed
Su, IC, Lee, KL, Liu, HY, Chuang, HC, Chen, LY, Lee, YJ. Severe community-acquired pneumonia due to Pseudomonas aeruginosa coinfection in an influenza A (H1N1)pdm09 patient. J Microbiol Immunol Infect 2019;52:365366.CrossRefGoogle Scholar
Rizzo, C, Caporali, MG, Rota, MC. Pandemic influenza and pneumonia due to Legionella pneumophila: a frequently underestimated coinfection. Clin Infect Dis 2010;51:115.10.1086/653444CrossRefGoogle ScholarPubMed
Jacobs, JH, Viboud, C, Tchetgen, ET, et al. The association of meningococcal disease with influenza in the United States, 1989–2009. PLoS One 2014;9:e107486.10.1371/journal.pone.0107486CrossRefGoogle ScholarPubMed
Dhanoa, A, Fang, NC, Hassan, SS, Kaniappan, P, Rajasekaram, G. Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection. Virol J 2011;8:501.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1)—United States, May–August 2009. Morb Mortal Wkly Rep 2009;58:10711074.Google Scholar
Cauley, LS, Vella, AT. Why is coinfection with influenza virus and bacteria so difficult to control? Discov Med 2015;19:3340.Google ScholarPubMed
van der Sluijs, KF, van der Poll, T, Lutter, R, Juffermans, NP, Schultz, MJ. Bench-to-bedside review: bacterial pneumonia with influenza—pathogenesis and clinical implications. Crit Care 2010;14:219.CrossRefGoogle ScholarPubMed
Short, KR, Kedzierska, K, van de Sandt, CE. Back to the future: lessons learned from the 1918 influenza pandemic. Front Cell Infect Microbiol 2018;8:343.10.3389/fcimb.2018.00343CrossRefGoogle Scholar
Rynda-Apple, A, Robinson, KM, Alcorn, JF. Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease. Infect Immun 2015;83:37643770.10.1128/IAI.00298-15CrossRefGoogle ScholarPubMed
Metlay, JP, Waterer, GW, Long, AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200:e45e67.CrossRefGoogle ScholarPubMed
Gupta, RK, George, R, Nguyen-Van-Tam, JS. Bacterial pneumonia and pandemic influenza planning. Emerg Infect Dis 2008;14:11871192.CrossRefGoogle ScholarPubMed
Uyeki, TM, Bernstein, HH, Bradley, JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaa. Clin Infect Dis 2019;68:895902.CrossRefGoogle Scholar
Rolfes, MA, Foppa, IM, Garg, S, et al. Annual estimates of the burden of seasonal influenza in the United States: a tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses 2018;12:132137.CrossRefGoogle ScholarPubMed
Klompas, M, Imrey, P, Yu, P-C, et al. Respiratory viral testing and antibacterial treatment in patients hospitalized with community-acquired pneumonia. Infect Control Hosp Epidemiol 2020. doi: 10.1017/ice.2020.1312.Google ScholarPubMed
Grizzle, JE, Starmer, CF, Koch, GG. Analysis of categorical data by linear models. Biometrics 1969;25:489504.10.2307/2528901CrossRefGoogle ScholarPubMed
SAS/STAT 14.3 User’s Guide: The CATMOD procedure. SAS Institute website. https://support.sas.com/documentation/onlinedoc/stat/143/catmod.pdf. Published 2017. Accessed March 15, 2021.Google Scholar
Elixhauser, A, Steiner, C, Harris, DR, Coffey, RM. Comorbidity measures for use with administrative data. Med Care 1998;36:827.CrossRefGoogle ScholarPubMed
Gagne, JJ, Glynn, RJ, Avorn, J, Levin, R, Schneeweiss, S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol 2011;64:749759.CrossRefGoogle ScholarPubMed
Rice, TW, Rubinson, L, Uyeki, TM. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med 2012;40:14871498.CrossRefGoogle ScholarPubMed
Grabowska, K, Högberg, LD, Penttinen, P, Svensson, A. Occurrence of invasive pneumococcal disease and number of excess cases due to influenza. BMC Infect Dis 2006;6:58.CrossRefGoogle ScholarPubMed
Morris, DE, Cleary, DW, Clarke, SC. Secondary bacterial infections associated with influenza pandemics. Front Microbiol 2017;8:1041.10.3389/fmicb.2017.01041CrossRefGoogle ScholarPubMed
Gill, JR, Sheng, ZM, Ely, SF, et al. Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections. Arch Pathol Lab Med 2010;134:235243.10.5858/134.2.235CrossRefGoogle ScholarPubMed
1
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Bacterial coinfection in influenza pneumonia: Rates, pathogens, and outcomes
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Bacterial coinfection in influenza pneumonia: Rates, pathogens, and outcomes
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Bacterial coinfection in influenza pneumonia: Rates, pathogens, and outcomes
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *