- Andrew J Stewardson1,2, Arthur Allignol3,4, Jan Beyersmann3, Nicholas Graves5, Martin Schumacher4, Rodolphe Meyer6, Evelina Tacconelli7,8, Giulia De Angelis7, Claudio Farina9, Fabio Pezzoli9, Xavier Bertrand10, Houssein Gbaguidi-Haore10, Jonathan Edgeworth11, Olga Tosas11, Jose A Martinez12, M Pilar Ayala-Blanco12, Angelo Pan13, Alessia Zoncada13, Charis A Marwick14, Dilip Nathwani14, Harald Seifert15,16, Nina Hos15, Stefan Hagel17, Mathias Pletz17, Stephan Harbarth1, the TIMBER Study Group18
-
View Affiliations Hide AffiliationsAffiliations: 1 Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland 2 Department of Medicine, University of Melbourne, Melbourne, Australia 3 Institute of Statistics, Ulm University, Ulm, Germany 4 Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Freiburg, Germany 5 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia 6 Information Technology, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland 7 Division of Infectious Diseases, Agostino Gemelli Hospital, Rome, Italy 8 Division of Infectious Diseases, DZIF TTU-HAARBI, University Hospital Tübingen, Tübingen, Germany 9 Papa Giovanni XXIII Hospital, Bergamo, Italy 10 Centre hospitalier régional et universitaire (CHRU) Besançon, Besançon, France 11 Department of Infectious Diseases, Kings College London, London, United Kingdom 12 Hospital Clinic de Barcelona, Barcelona, Spain 13 Istituti Ospitalieri di Cremona, Cremona, Italy 14 Department of Infection and Immunodeficiency, Ninewells Hospital and Medical School, Dundee, United Kingdom 15 Uniklinik Köln, Cologne, Germany 16 German Centre for Infection Research (DZIF), Braunschweig, Germany 17 Center for Infectious Diseases and Infection Control, University Hospital Jena, Jena, Germany 18 The members of the group are listed at the end of the articleAndrew J. Stewardsonandrew.stew rdson.net
-
View Citation Hide Citation
Citation style for this article: Stewardson Andrew J, Allignol Arthur, Beyersmann Jan, Graves Nicholas, Schumacher Martin, Meyer Rodolphe, Tacconelli Evelina, De Angelis Giulia, Farina Claudio, Pezzoli Fabio, Bertrand Xavier, Gbaguidi-Haore Houssein, Edgeworth Jonathan, Tosas Olga, Martinez Jose A, Ayala-Blanco M Pilar, Pan Angelo, Zoncada Alessia, Marwick Charis A, Nathwani Dilip, Seifert Harald, Hos Nina, Hagel Stefan, Pletz Mathias, Harbarth Stephan, the TIMBER Study Group. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. Euro Surveill. 2016;21(33):pii=30319. https://doi.org/10.2807/1560-7917.ES.2016.21.33.30319 Received: 23 Sep 2015; Accepted: 20 Apr 2016
The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study
Abstract
We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34–2.42, HR = 1.81; 95% CI: 1.49–2.20 and HR = 2.42; 95% CI: 1.66–3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2–9.4, 11.5 days; 95% CI: 11.5–11.6 and 13.3 days; 95% CI: 13.2–13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8–5.9) but not hazard of death (1.16; 95% CI: 0.98–1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13–2.35), excess LOS (4.9 days; 95% CI: 1.1–8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.

Article metrics loading...

-
From This Site
/content/10.2807/1560-7917.ES.2016.21.33.30319dcterms_title,dcterms_subject,pub_keyword105 -
PubMed
-
Google Scholar

Full text loading...
References
-
World Health Organization (WHO). Antimicrobial resistance: global report on surveillance 2014. Geneva: WHO Press, 2014. Available from: http://www.who.int/drugresistance/documents/surveillancereport/en/
-
Risks G. 2014. 9th edition. Geneva: World Economic Forum; 2014. Available from: http://reports.weforum.org/global-risks-2014/
-
Laxminarayan R, Duse A, Wattal C, Zaidi AK, Wertheim HF, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013;13(12):1057-98. https://doi.org/10.1016/S1473-3099(13)70318-9 PMID: 24252483
-
Beyersmann J, Wolkewitz M, Allignol A, Grambauer N, Schumacher M. Application of multistate models in hospital epidemiology: advances and challenges. Biom J. 2011;53(2):332-50. https://doi.org/10.1002/bimj.201000146 PMID: 21374697
-
Gandra S, Barter DM, Laxminarayan R. Economic burden of antibiotic resistance: how much do we really know? Clin Microbiol Infect. 2014;20(10):973-80. https://doi.org/10.1111/1469-0691.12798 PMID: 25273968
-
Graves N, Harbarth S, Beyersmann J, Barnett A, Halton K, Cooper B. Estimating the cost of health care-associated infections: mind your p’s and q’s. Clin Infect Dis. 2010;50(7):1017-21. https://doi.org/10.1086/651110 PMID: 20178419
-
Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum β-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev. 2013;26(4):744-58. https://doi.org/10.1128/CMR.00023-13 PMID: 24092853
-
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-7. https://doi.org/10.1016/S0140-6736(07)61602-X PMID: 18064739
-
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. https://doi.org/10.1016/0021-9681(87)90171-8 PMID: 3558716
-
Cohen AL, Calfee D, Fridkin SK, Huang SS, Jernigan JA, Lautenbach E, et al. Recommendations for metrics for multidrug-resistant organisms in healthcare settings: SHEA/HICPAC Position paper. Infect Control Hosp Epidemiol. 2008;29(10):901-13. https://doi.org/10.1086/591741 PMID: 18808340
-
Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130-9. https://doi.org/10.1097/01.mlr.0000182534.19832.83 PMID: 16224307
-
Stewardson A, Fankhauser C, De Angelis G, Rohner P, Safran E, Schrenzel J, et al. Burden of bloodstream infection caused by extended-spectrum β-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University Hospital and a nationwide predictive model. Infect Control Hosp Epidemiol. 2013;34(2):133-43. https://doi.org/10.1086/669086 PMID: 23295559
-
Aalen O, Johansen S. An empirical transition matrix for non-homogeneous Markov chains based on censored observations. Scand J Stat. 1978;5:141-50.
-
Andersen PK, Perme MP. Pseudo-observations in survival analysis. Stat Methods Med Res. 2010;19(1):71-99. https://doi.org/10.1177/0962280209105020 PMID: 19654170
-
Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986;73(1):13-22. https://doi.org/10.1093/biomet/73.1.13
-
Lunn D, Jackson C, Best N, Thomas A, Spiegelhalter D. The BUGS Book: A practical introduction to Bayesian Analysis. London: CRC Press / Chapman and Hall, 2012.
-
Stewardson AJ, Harbarth S, Graves NTIMBER Study Group. Valuation of hospital bed-days released by infection control programs: a comparison of methods. Infect Control Hosp Epidemiol. 2014;35(10):1294-7. https://doi.org/10.1086/678063 PMID: 25203185
-
Beyersmann J, Allignol A, Schumacher M. Competing risks and multistate models with R. Berlin: Springer, 2012.
-
Beyersmann J, Gastmeier P, Schumacher M. Incidence in ICU populations: how to measure and report it? Intensive Care Med. 2014;40(6):871-6. https://doi.org/10.1007/s00134-014-3279-7 PMID: 24817028
-
Beyersmann J, Gastmeier P, Grundmann H, Bärwolff S, Geffers C, Behnke M, et al. Transmission-associated nosocomial infections: prolongation of intensive care unit stay and risk factor analysis using multistate models. Am J Infect Control. 2008;36(2):98-103. https://doi.org/10.1016/j.ajic.2007.06.007 PMID: 18313511
-
Graves N. Economics and preventing hospital-acquired infection. Emerg Infect Dis. 2004;10(4):561-6. https://doi.org/10.3201/eid1004.020754 PMID: 15200842
-
de Kraker ME, Wolkewitz M, Davey PG, Grundmann HBURDEN Study Group. Clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin-resistant Staphylococcus aureus bloodstream infections. Antimicrob Agents Chemother. 2011;55(4):1598-605. https://doi.org/10.1128/AAC.01157-10 PMID: 21220533
-
de Kraker ME, Wolkewitz M, Davey PG, Koller W, Berger J, Nagler J, et al. Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins. J Antimicrob Chemother. 2011;66(2):398-407. https://doi.org/10.1093/jac/dkq412 PMID: 21106563
-
Lambert ML, Suetens C, Savey A, Palomar M, Hiesmayr M, Morales I, et al. Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet Infect Dis. 2011;11(1):30-8. https://doi.org/10.1016/S1473-3099(10)70258-9 PMID: 21126917
-
Kieszak SM, Flanders WD, Kosinski AS, Shipp CC, Karp H. A comparison of the Charlson comorbidity index derived from medical record data and administrative billing data. J Clin Epidemiol. 1999;52(2):137-42. https://doi.org/10.1016/S0895-4356(98)00154-1 PMID: 10201654
-
Luthi JC, Troillet N, Eisenring MC, Sax H, Burnand B, Quan H, et al. Administrative data outperformed single-day chart review for comorbidity measure. Int J Qual Health Care. 2007;19(4):225-31. https://doi.org/10.1093/intqhc/mzm017 PMID: 17599922
-
Rottier WC, Ammerlaan HS, Bonten MJ. Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis. J Antimicrob Chemother. 2012;67(6):1311-20. https://doi.org/10.1093/jac/dks065 PMID: 22396430
-
Leibovici L. Long-term consequences of severe infections. Clin Microbiol Infect. 2013;19(6):510-2. https://doi.org/10.1111/1469-0691.12160 PMID: 23397980
-
Smith R, Coast J. The true cost of antimicrobial resistance. BMJ. 2013;346:f1493. https://doi.org/10.1136/bmj.f1493 PMID: 23479660
-
Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. London; 2014. Available from: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf
-
de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N, Grundmann H. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013;19(9):860-8. https://doi.org/10.1111/1469-0691.12028 PMID: 23039210
-
Ammerlaan HS, Harbarth S, Buiting AG, Crook DW, Fitzpatrick F, Hanberger H, et al. Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin Infect Dis. 2013;56(6):798-805. https://doi.org/10.1093/cid/cis1006 PMID: 23223600

Data & Media loading...
