Abstract

Background: Effective treatment using antibiotic vancomycin requires close monitoring of serum drug levels due to its narrow therapeutic index. In the current practice, physicians use various dosing algorithms for dosage titration, but these algorithms reported low success in achieving therapeutic targets. We explored using artificial intelligent to assist vancomycin dosage titration. Methods: We used a novel method to generate the label for each record and only included records with appropriate label data to generate a clean cohort with 2,282 patients and 7,912 injection records. Among them, 64% of patients were used to train two machine learning models, one for initial dose recommendation and another for subsequent dose recommendation. The model performance was evaluated using two metrics: PAR, a pharmacology meaningful metric defined by us, and Mean Absolute Error (MAE), a commonly used regression metric. Results: In our 3-year data, only a small portion (34.1%) of current injection doses could reach the desired vancomycin trough level (14–20 mcg/ml). Both PAR and MAE of our machine learning models were better than the classical pharmacokinetic models. Our model also showed better performance than the other previously developed machine learning models in our test data. Conclusion: We developed machine learning models to recommend vancomycin dosage. Our results show that the new AI-assisted dosage titration approach has the potential to improve the traditional approaches. This is especially useful to guide decision making for inexperienced doctors in making consistent and safe dosing recommendations for high-risk medications like vancomycin.

Highlights

  • Vancomycin is a glycopeptide antibiotic commonly used in the treatment of Gram-positive infections, especially methicillin-resistant Staphylococcus aureus (MRSA)

  • In the 3 years’ (Jan 2017 ~ Dec 2019) data collected from Singapore General Hospital, we filtered out the records in which the duration between vancomycin lab test and its closest prior injection were not in the reasonable intervals because only the vancomycin lab tests at the specific time interval after injections was considered to properly reflect the impact of current injections, and considered as the vancomycin trough level

  • We used target trough vancomycin levels instead of the latest recommended AUC-guided approach. This was mainly because our institutional practice still adopts trough level–guided dosage titration, which is widely used in many institutions in the world

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Summary

Introduction

Vancomycin is a glycopeptide antibiotic commonly used in the treatment of Gram-positive infections, especially methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin therapy requires close monitoring of serum drug levels in view of its narrow therapeutic index. High serum drug levels increase the risk for nephrotoxicity, while low serum drug levels lead to AI-Based Vancomycin Dosage Recommendation reduced efficacy. The current practice recommends regular monitoring of serum trough levels at a steady state, aiming at a narrow range of 15–20 mg/L for the treatment of MRSA infections. In the latest guidelines on therapeutic drug monitoring of vancomycin, an AUC (area under curve)-guided dosing and monitoring approach was recommended using an individualized target of the AUC/MIC ratio of 400–600 (Rybak et al, 2020). Effective treatment using antibiotic vancomycin requires close monitoring of serum drug levels due to its narrow therapeutic index. Physicians use various dosing algorithms for dosage titration, but these algorithms reported low success in achieving therapeutic targets. We explored using artificial intelligent to assist vancomycin dosage titration

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