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

Objectives: Phenotypical 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. Methods: Data 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. Results: XGBoost 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 Conclusion: ML-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.