Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results

ObjectivesPhenotypical Extended Spectrum β-Lactamase (ESBL)-production is commonly determined using the combination disk diffusion test or gradient test. This requires overnight incubation, prolonging time-to-detection and increasing duration of empirical treatment for patients with infections cause...

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Main Authors: Y. El Ghouch, M. C. Schut, K. C. E. Sigaloff, W. Altorf-Van Der Kuil, J. M. Prins, R. P. Schade, the ISIS-AR study group, J.W.T. Cohen Stuart, D.C. Melles, K. van Dijk, A. Alzubaidy, M. Scholing, S.D. Kuil, G.J. Blaauw, W. Altorf, van der Kuil, S.M. Bierman, S.C. de Greeff, S.R. Groenendijk, R. Hertroys, L. Kruithof, I.M. Nauta, D.W. Notermans, J. Polman, W.J. van den Reek, A.F. Schoffelen, F. Velthuis, C.C.H. Wielders, B.J. de Wit, R.E. Zoetigheid, W. van den Bijllaardt, E.M. Kraan, M.B. Haeseker, J.M. da Silva, E. de Jong, B. Maraha, A.J. van Griethuysen, B.B. Wintermans, M.J.C.A. van Trijp, A.E. Muller, M. Wong, A. Ott, E. Bathoorn, M. Lokate, J. Sinnige, L. Bank, N.H. Renders, J.W. Dorigo-Zetsma, L.J. Bakker, W. Ang, K. Waar, M.T. van der Beek, M.A. Leversteijn-van Hall, S.P. van Mens, E. Schaftenaar, M.H. Nabuurs-Franssen, I. Maat, P.D.J. Sturm, B.M.W. Diederen, L.G.M. Bode, D.S.Y. Ong, M. van Rijn, S. Dinant, M. den Reijer, D.W. van Dam, E.I.G.B. de Brauwer, R.G. Bentvelsen, A.L.M. Vlek, M. de Graaf, A. Troelstra, K.B. Gast, M.P.A. van Meer, J. de Vries, J.D. Machiels
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Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1582703/full
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author Y. El Ghouch
Y. El Ghouch
M. C. Schut
K. C. E. Sigaloff
W. Altorf-Van Der Kuil
J. M. Prins
R. P. Schade
R. P. Schade
the ISIS-AR study group
J.W.T. Cohen Stuart
D.C. Melles
K. van Dijk
A. Alzubaidy
M. Scholing
S.D. Kuil
G.J. Blaauw
W. Altorf
van der Kuil
S.M. Bierman
S.C. de Greeff
S.R. Groenendijk
R. Hertroys
L. Kruithof
I.M. Nauta
D.W. Notermans
J. Polman
W.J. van den Reek
A.F. Schoffelen
F. Velthuis
C.C.H. Wielders
B.J. de Wit
R.E. Zoetigheid
W. van den Bijllaardt
E.M. Kraan
M.B. Haeseker
J.M. da Silva
E. de Jong
B. Maraha
A.J. van Griethuysen
B.B. Wintermans
M.J.C.A. van Trijp
A.E. Muller
M. Wong
A. Ott
E. Bathoorn
M. Lokate
J. Sinnige
D.C. Melles
L. Bank
N.H. Renders
J.W. Dorigo-Zetsma
L.J. Bakker
W. Ang
K. Waar
M.T. van der Beek
M.A. Leversteijn-van Hall
S.P. van Mens
E. Schaftenaar
M.H. Nabuurs-Franssen
I. Maat
P.D.J. Sturm
B.M.W. Diederen
L.G.M. Bode
D.S.Y. Ong
M. van Rijn
S. Dinant
M. den Reijer
D.W. van Dam
E.I.G.B. de Brauwer
R.G. Bentvelsen
A.L.M. Vlek
M. de Graaf
A. Troelstra
K.B. Gast
M.P.A. van Meer
J. de Vries
J.D. Machiels
author_facet Y. El Ghouch
Y. El Ghouch
M. C. Schut
K. C. E. Sigaloff
W. Altorf-Van Der Kuil
J. M. Prins
R. P. Schade
R. P. Schade
the ISIS-AR study group
J.W.T. Cohen Stuart
D.C. Melles
K. van Dijk
A. Alzubaidy
M. Scholing
S.D. Kuil
G.J. Blaauw
W. Altorf
van der Kuil
S.M. Bierman
S.C. de Greeff
S.R. Groenendijk
R. Hertroys
L. Kruithof
I.M. Nauta
D.W. Notermans
J. Polman
W.J. van den Reek
A.F. Schoffelen
F. Velthuis
C.C.H. Wielders
B.J. de Wit
R.E. Zoetigheid
W. van den Bijllaardt
E.M. Kraan
M.B. Haeseker
J.M. da Silva
E. de Jong
B. Maraha
A.J. van Griethuysen
B.B. Wintermans
M.J.C.A. van Trijp
A.E. Muller
M. Wong
A. Ott
E. Bathoorn
M. Lokate
J. Sinnige
D.C. Melles
L. Bank
N.H. Renders
J.W. Dorigo-Zetsma
L.J. Bakker
W. Ang
K. Waar
M.T. van der Beek
M.A. Leversteijn-van Hall
S.P. van Mens
E. Schaftenaar
M.H. Nabuurs-Franssen
I. Maat
P.D.J. Sturm
B.M.W. Diederen
L.G.M. Bode
D.S.Y. Ong
M. van Rijn
S. Dinant
M. den Reijer
D.W. van Dam
E.I.G.B. de Brauwer
R.G. Bentvelsen
A.L.M. Vlek
M. de Graaf
A. Troelstra
K.B. Gast
M.P.A. van Meer
J. de Vries
J.D. Machiels
author_sort Y. El Ghouch
collection DOAJ
description ObjectivesPhenotypical Extended Spectrum β-Lactamase (ESBL)-production is commonly determined using the combination disk diffusion test or gradient test. This requires overnight incubation, prolonging time-to-detection and increasing duration of empirical treatment for patients with infections caused by gram-negative bacteria. To achieve instant confirmation without incubation, we developed a machine learning (ML)-model that predicts phenotypic ESBL-confirmation using Minimum Inhibitory Concentrations from routine automated antimicrobial susceptibility testing (AST)-results.MethodsData from the Dutch national laboratory-based surveillance system ISIS-AR collected between 2013 and 2022 from 49 laboratories were used: 178,044 isolates of E. coli (141,576), K. pneumoniae (33,088), and P. mirabilis (3,380) that exhibited resistance to cefotaxime and/or ceftazidime, and had available results of phenotypical ESBL-confirmation testing. We evaluated Logistic Regression, Random Forest and XGBoost models and calculated SHAP-values (SHapley Additive exPlanations) to identify most contributing features. We externally validated models using 5,996 isolates collected in Amsterdam University Medical Centres’ between 2013 and 2022.ResultsXGBoost achieved an AUROC (Area Under Receiver Operating Characteristics) of 0.97, a sensitivity of 0.89 and an accuracy of 0.93. The most contributing features were the antibiotics cefotaxime, cefoxitin and trimethoprim for E. coli and K. pneumoniae, and cefuroxime, imipenem and cefotaxime for P. mirabilis. External validation yielded AUROCs of 0.93 (E. coli), 0.89 (K. pneumoniae) and 0.93 (P. mirabilis).ConclusionML-models for prediction of ESBL-production using routine AST-system data achieved high performances. Implementing these models in laboratory practice could shorten time-to-detection. Once deployed, this approach could facilitate widespread screening for phenotypic ESBL-production.
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spelling doaj-art-847feb182c134d15b1cb4497b15380362025-08-20T02:28:55ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15827031582703Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing resultsY. El Ghouch0Y. El Ghouch1M. C. Schut2K. C. E. Sigaloff3W. Altorf-Van Der Kuil4J. M. Prins5R. P. Schade6R. P. Schade7the ISIS-AR study groupJ.W.T. Cohen StuartD.C. MellesK. van DijkA. AlzubaidyM. ScholingS.D. KuilG.J. BlaauwW. Altorf van der KuilS.M. BiermanS.C. de GreeffS.R. GroenendijkR. HertroysL. KruithofI.M. NautaD.W. NotermansJ. PolmanW.J. van den ReekA.F. SchoffelenF. VelthuisC.C.H. WieldersB.J. de WitR.E. ZoetigheidW. van den BijllaardtE.M. KraanM.B. HaesekerJ.M. da SilvaE. de JongB. MarahaA.J. van GriethuysenB.B. WintermansM.J.C.A. van TrijpA.E. MullerM. WongA. OttE. BathoornM. LokateJ. SinnigeD.C. MellesL. BankN.H. RendersJ.W. Dorigo-ZetsmaL.J. BakkerW. AngK. WaarM.T. van der BeekM.A. Leversteijn-van HallS.P. van MensE. SchaftenaarM.H. Nabuurs-FranssenI. MaatP.D.J. SturmB.M.W. DiederenL.G.M. BodeD.S.Y. OngM. van RijnS. DinantM. den ReijerD.W. van DamE.I.G.B. de BrauwerR.G. BentvelsenA.L.M. VlekM. de GraafA. TroelstraK.B. GastM.P.A. van MeerJ. de VriesJ.D. MachielsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Internal Medicine, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Laboratory Medicine, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Internal Medicine, Amsterdam UMC, Amsterdam, NetherlandsCentre for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, NetherlandsDepartment of Internal Medicine, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Internal Medicine, Amsterdam UMC, Amsterdam, NetherlandsObjectivesPhenotypical Extended Spectrum β-Lactamase (ESBL)-production is commonly determined using the combination disk diffusion test or gradient test. This requires overnight incubation, prolonging time-to-detection and increasing duration of empirical treatment for patients with infections caused by gram-negative bacteria. To achieve instant confirmation without incubation, we developed a machine learning (ML)-model that predicts phenotypic ESBL-confirmation using Minimum Inhibitory Concentrations from routine automated antimicrobial susceptibility testing (AST)-results.MethodsData from the Dutch national laboratory-based surveillance system ISIS-AR collected between 2013 and 2022 from 49 laboratories were used: 178,044 isolates of E. coli (141,576), K. pneumoniae (33,088), and P. mirabilis (3,380) that exhibited resistance to cefotaxime and/or ceftazidime, and had available results of phenotypical ESBL-confirmation testing. We evaluated Logistic Regression, Random Forest and XGBoost models and calculated SHAP-values (SHapley Additive exPlanations) to identify most contributing features. We externally validated models using 5,996 isolates collected in Amsterdam University Medical Centres’ between 2013 and 2022.ResultsXGBoost achieved an AUROC (Area Under Receiver Operating Characteristics) of 0.97, a sensitivity of 0.89 and an accuracy of 0.93. The most contributing features were the antibiotics cefotaxime, cefoxitin and trimethoprim for E. coli and K. pneumoniae, and cefuroxime, imipenem and cefotaxime for P. mirabilis. External validation yielded AUROCs of 0.93 (E. coli), 0.89 (K. pneumoniae) and 0.93 (P. mirabilis).ConclusionML-models for prediction of ESBL-production using routine AST-system data achieved high performances. Implementing these models in laboratory practice could shorten time-to-detection. Once deployed, this approach could facilitate widespread screening for phenotypic ESBL-production.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1582703/fullESBLmachine learningantimicrobial resistancebacteriasurveillance
spellingShingle Y. El Ghouch
Y. El Ghouch
M. C. Schut
K. C. E. Sigaloff
W. Altorf-Van Der Kuil
J. M. Prins
R. P. Schade
R. P. Schade
the ISIS-AR study group
J.W.T. Cohen Stuart
D.C. Melles
K. van Dijk
A. Alzubaidy
M. Scholing
S.D. Kuil
G.J. Blaauw
W. Altorf
van der Kuil
S.M. Bierman
S.C. de Greeff
S.R. Groenendijk
R. Hertroys
L. Kruithof
I.M. Nauta
D.W. Notermans
J. Polman
W.J. van den Reek
A.F. Schoffelen
F. Velthuis
C.C.H. Wielders
B.J. de Wit
R.E. Zoetigheid
W. van den Bijllaardt
E.M. Kraan
M.B. Haeseker
J.M. da Silva
E. de Jong
B. Maraha
A.J. van Griethuysen
B.B. Wintermans
M.J.C.A. van Trijp
A.E. Muller
M. Wong
A. Ott
E. Bathoorn
M. Lokate
J. Sinnige
D.C. Melles
L. Bank
N.H. Renders
J.W. Dorigo-Zetsma
L.J. Bakker
W. Ang
K. Waar
M.T. van der Beek
M.A. Leversteijn-van Hall
S.P. van Mens
E. Schaftenaar
M.H. Nabuurs-Franssen
I. Maat
P.D.J. Sturm
B.M.W. Diederen
L.G.M. Bode
D.S.Y. Ong
M. van Rijn
S. Dinant
M. den Reijer
D.W. van Dam
E.I.G.B. de Brauwer
R.G. Bentvelsen
A.L.M. Vlek
M. de Graaf
A. Troelstra
K.B. Gast
M.P.A. van Meer
J. de Vries
J.D. Machiels
Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
Frontiers in Microbiology
ESBL
machine learning
antimicrobial resistance
bacteria
surveillance
title Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
title_full Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
title_fullStr Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
title_full_unstemmed Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
title_short Rapid extended-spectrum beta-lactamase-confirmation by using a machine learning model directly on routine automated susceptibility testing results
title_sort rapid extended spectrum beta lactamase confirmation by using a machine learning model directly on routine automated susceptibility testing results
topic ESBL
machine learning
antimicrobial resistance
bacteria
surveillance
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1582703/full
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