Research Open Access
Like 0



Algorithms for predicting infection with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) on hospital admission or in patients with bacteraemia have been proposed, aiming to optimise empiric treatment decisions.


We sought to confirm external validity and transferability of two published prediction models as well as their integral components.


We performed a retrospective case–control study at University Hospital Basel, Switzerland. Consecutive patients with ESBL-producing or isolated from blood samples between 1 January 2010 and 31 December 2016 were included. For each case, three non-ESBL-producing controls matching for date of detection and bacterial species were identified. The main outcome measure was the ability to accurately predict infection with ESBL-PE by measures of discrimination and calibration.


Overall, 376 patients (94 patients, 282 controls) were analysed. Performance measures for prediction of ESBL-PE infection of both prediction models indicate adequate measures of calibration, but poor discrimination (area under receiver-operating curve: 0.627 and 0.651). History of ESBL-PE colonisation or infection was the single most predictive independent risk factor for ESBL-PE infection with high specificity (97%), low sensitivity (34%) and balanced positive and negative predictive values (80% and 82%).


Applying published prediction models to institutions these were not derived from, may result in substantial misclassification of patients considered as being at risk, potentially leading to wrong allocation of antibiotic treatment, negatively affecting patient outcomes and overall resistance rates in the long term. Future prediction models need to address differences in local epidemiology by allowing for customisation according to different settings.


Article metrics loading...

Loading full text...

Full text loading...



  1. Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8(3):159-66.  https://doi.org/10.1016/S1473-3099(08)70041-0  PMID: 18291338 
  2. Coque TM, Baquero F, Canton R. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro Surveill. 2008;13(47):19044. PMID: 19021958 
  3. European Centre for Disease Prevention and Control (ECDC). Annual epidemiological report 2014. Antimicrobial resistance and healthcare-associated infections. Stockholm: ECDC; 2015. Available from: https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance-and-healthcare-associated-infections-annual#no-link
  4. Doi Y, Park YS, Rivera JI, Adams-Haduch JM, Hingwe A, Sordillo EM, et al. Community-associated extended-spectrum β-lactamase-producing Escherichia coli infection in the United States. Clin Infect Dis. 2013;56(5):641-8.  https://doi.org/10.1093/cid/cis942  PMID: 23150211 
  5. Castanheira M, Farrell SE, Krause KM, Jones RN, Sader HS. Contemporary diversity of β-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups. Antimicrob Agents Chemother. 2014;58(2):833-8.  https://doi.org/10.1128/AAC.01896-13  PMID: 24247134 
  6. Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: A randomized clinical trial. JAMA. 2018;320(10):984-94.  https://doi.org/10.1001/jama.2018.12163  PMID: 30208454 
  7. Souverein D, Euser SM, van der Reijden WA, Herpers BL, Kluytmans J, Rossen JWA, et al. Clinical sensitivity and specificity of the Check-Points Check-Direct ESBL Screen for BD MAX, a real-time PCR for direct ESBL detection from rectal swabs. J Antimicrob Chemother. 2017;72(9):2512-8.  https://doi.org/10.1093/jac/dkx189  PMID: 28633496 
  8. Palacios-Baena ZR, Gutiérrez-Gutiérrez B, De Cueto M, Viale P, Venditti M, Hernández-Torres A, et al. Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-β-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother. 2017;72(3):906-13.  https://doi.org/10.1093/jac/dkw513  PMID: 28062685 
  9. 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 
  10. Lodise TP, Zhao Q, Fahrbach K, Gillard PJ, Martin A. A systematic review of the association between delayed appropriate therapy and mortality among patients hospitalized with infections due to Klebsiella pneumoniae or Escherichia coli: how long is too long? BMC Infect Dis. 2018;18(1):625.  https://doi.org/10.1186/s12879-018-3524-8  PMID: 30518337 
  11. Tumbarello M, Trecarichi EM, Bassetti M, De Rosa FG, Spanu T, Di Meco E, et al. Identifying patients harboring extended-spectrum-beta-lactamase-producing Enterobacteriaceae on hospital admission: derivation and validation of a scoring system. Antimicrob Agents Chemother. 2011;55(7):3485-90.  https://doi.org/10.1128/AAC.00009-11  PMID: 21537020 
  12. Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH, et al. A clinical decision tree to predict whether a bacteremic patient is infected with an extended-spectrum β-lactamase-producing organism. Clin Infect Dis. 2016;63(7):896-903.  https://doi.org/10.1093/cid/ciw425  PMID: 27358356 
  13. Johnson SW, Anderson DJ, May DB, Drew RH. Utility of a clinical risk factor scoring model in predicting infection with extended-spectrum β-lactamase-producing enterobacteriaceae on hospital admission. Infect Control Hosp Epidemiol. 2013;34(4):385-92.  https://doi.org/10.1086/669858  PMID: 23466912 
  14. Vandenbroucke JP. STREGA, STROBE, STARD, SQUIRE, MOOSE, PRISMA, GNOSIS, TREND, ORION, COREQ, QUOROM, REMARK... and CONSORT: for whom does the guideline toll? J Clin Epidemiol. 2009;62(6):594-6.  https://doi.org/10.1016/j.jclinepi.2008.12.003  PMID: 19181482 
  15. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. 28th edition. Wayne: CLSI; 2018. Available from: http://iacld.ir/DL/public/CLSI-2018-M100-S28.pdf
  16. Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc B. 1996;58(1):267-88.  https://doi.org/10.1111/j.2517-6161.1996.tb02080.x 
  17. Townsend W. ELASTICREGRESS: Stata module to perform elastic net regression, lasso regression, ridge regression. Statistical Software Components S458397. Boston: Boston College Department of Economics. [Accessed: 28 Jun 2020]. Available from: https://ideas.repec.org/c/boc/bocode/s458397.html
  18. Biggs D, De Ville B, Suen E. A method of choosing multiway partitions for classification and decision trees. J Appl Stat. 1991;18(1):49-62.  https://doi.org/10.1080/02664769100000005 
  19. Luchman JN. CHAID: Stata module to conduct chi-square automated interaction detection. Statistical Software Components S457752. Boston: Boston College Department of Economics. [Accessed: 28 Jun 2020]. Available from: https://ideas.repec.org/c/boc/bocode/s457752.html
  20. Nattino G, Finazzi S, Bertolini G. A new calibration test and a reappraisal of the calibration belt for the assessment of prediction models based on dichotomous outcomes. Stat Med. 2014;33(14):2390-407.  https://doi.org/10.1002/sim.6100  PMID: 24497413 
  21. Rodríguez-Baño J, Picón E, Gijón P, Hernández JR, Ruíz M, Peña C, et al. Community-onset bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: risk factors and prognosis. Clin Infect Dis. 2010;50(1):40-8.  https://doi.org/10.1086/649537  PMID: 19995215 
  22. Kang CI, Wi YM, Lee MY, Ko KS, Chung DR, Peck KR, et al. Epidemiology and risk factors of community onset infections caused by extended-spectrum β-lactamase-producing Escherichia coli strains. J Clin Microbiol. 2012;50(2):312-7.  https://doi.org/10.1128/JCM.06002-11  PMID: 22162561 
  23. Ben-Ami R, Rodríguez-Baño J, Arslan H, Pitout JD, Quentin C, Calbo ES, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009;49(5):682-90.  https://doi.org/10.1086/604713  PMID: 19622043 
  24. Rodríguez-Baño J, Alcalá JC, Cisneros JM, Grill F, Oliver A, Horcajada JP, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med. 2008;168(17):1897-902.  https://doi.org/10.1001/archinte.168.17.1897  PMID: 18809817 
  25. Pitout JD, Nordmann P, Laupland KB, Poirel L. Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother. 2005;56(1):52-9.  https://doi.org/10.1093/jac/dki166  PMID: 15917288 
  26. Platteel TN, Leverstein-van Hall MA, Cohen Stuart JW, Thijsen SF, Mascini EM, van Hees BC, et al. Predicting carriage with extended-spectrum beta-lactamase-producing bacteria at hospital admission: a cross-sectional study. Clin Microbiol Infect. 2015;21(2):141-6.  https://doi.org/10.1016/j.cmi.2014.09.014  PMID: 25658554 
  27. Denis B, Lafaurie M, Donay JL, Fontaine JP, Oksenhendler E, Raffoux E, et al. Prevalence, risk factors, and impact on clinical outcome of extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia: a five-year study. Int J Infect Dis. 2015;39:1-6.  https://doi.org/10.1016/j.ijid.2015.07.010  PMID: 26189774 
  28. Augustine MR, Testerman TL, Justo JA, Bookstaver PB, Kohn J, Albrecht H, et al. Clinical risk score for prediction of extended-spectrum β-lactamase-producing Enterobacteriaceae in bloodstream isolates. Infect Control Hosp Epidemiol. 2017;38(3):266-72.  https://doi.org/10.1017/ice.2016.292  PMID: 27989244 
  29. Swiss Centre for Antibiotic resistance. Resistance Data Human Medicine. [Accessed: 28 June 2020]. Available from: https://www.anresis.ch/antibiotic-resistance/resistance-data-human-medicine/interactive-database-query/
  30. European Centre for Disease Prevention and Control (ECDC). Data from the ECDC Surveillance Atlas - Antimicrobial resistance. Stockholm; ECDC. [Accessed: 28 Jun 2020]. Available from: https://ecdc.europa.eu/en/antimicrobial-resistance/surveillance-and-disease-data/data-ecdc
  31. United States Centers for Disease Control and Prevention (US CDC). Antibiotic resistance threats in the United States, 2013. Atlanta: US CDC; 2013. Available from: https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
  32. Goodman KE, Simner PJ, Klein EY, Kazmi AQ, Gadala A, Toerper MF, et al. Predicting probability of perirectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and other carbapenem-resistant organisms (CROs) at hospital unit admission. Infect Control Hosp Epidemiol. 2019;40(5):541-50.  https://doi.org/10.1017/ice.2019.42  PMID: 30915928 
  33. European Centre for Disease Prevention and Control (ECDC). Surveillance of antimicrobial resistance in Europe – Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017. Stockholm: ECDC; 2018. Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-resistance-europe-2017
  34. Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3--From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med. 2005;31(10):1345-55.  https://doi.org/10.1007/s00134-005-2763-5  PMID: 16132892 
  35. Sakr Y, Krauss C, Amaral AC, Réa-Neto A, Specht M, Reinhart K, et al. Comparison of the performance of SAPS II, SAPS 3, APACHE II, and their customized prognostic models in a surgical intensive care unit. Br J Anaesth. 2008;101(6):798-803.  https://doi.org/10.1093/bja/aen291  PMID: 18845649 
  36. Thaden JT, Fowler VG Jr, Sexton DJ, Anderson DJ. Increasing incidence of extended-spectrum β-lactamase-producing Escherichia coli in community hospitals throughout the southeastern United States. Infect Control Hosp Epidemiol. 2016;37(1):49-54.  https://doi.org/10.1017/ice.2015.239  PMID: 26458226 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error