Exploring the Utility of MALDI-TOF Mass Spectrometry and Antimicrobial Resistance in Hospital Outbreak Detection

Rapid identification of outbreaks in hospitals is essential for controlling pathogens with epidemic potential. Although whole genome sequencing (WGS) remains the gold standard in outbreak investigations, its substantial costs and turnaround times limit its feasibility for routine surveillance, especially in less-equipped facilities. We explore three modalities as rapid alternatives: matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, antimicrobial resistance (AR) patterns, and electronic health records (EHR). We present a machine learning approach that learns discriminative features from these modalities to support outbreak detection. Multi-species evaluation shows that the integration of these modalities can boost outbreak detection performance. We also propose a tiered surveillance paradigm that can reduce the need for WGS through these alternative modalities. Further analysis of EHR information identifies potentially high-risk contamination routes linked to specific clinical procedures, notably those involving invasive equipment and high-frequency workflows, providing infection prevention teams with actionable targets for proactive risk mitigation

Machine learning models for MALDI-TOF mass spectrometry have shown considerable promise for clinical microbiology tasks such as microbial identification and antimicrobial resistance prediction. However, their deployment across institutions remains limited by domain shift, as acquisition-specific variability often leads models to capture technical artifacts rather than transferable biological information. Existing representation learning approaches primarily address this problem through statistical domain alignment while largely overlooking the biological supervision naturally available in microbiology datasets. We introduce DALMA, a probabilistic representation learning framework that jointly models acquisition-specific variability and biological supervision to learn biologically structured latent representations. By combining domain-specific reconstruction with biologically guided representation learning, DALMA learns transferable representations that generalize across heterogeneous clinical centers without requiring institution-specific components at inference, enabling zero-shot deployment on previously unseen sites. We evaluate DALMA on a multi-center benchmark comprising seven datasets from three countries. DALMA consistently achieves state-of-the-art zero-shot microbial identification across two held-out clinical centers, while the learned representations also transfer effectively to antimicrobial resistance prediction. Furthermore, latent-space novelty estimation enables reliable selective prediction under previously unseen domain shifts. These results demonstrate that biologically informed representation learning provides an effective strategy for robust and transferable ML in clinical microbiology.

Background: Antimicrobial resistance (AMR) is a global health threat. While the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) provides standardized data, population-level machine learning forecasting of resistance trends remains limited. Translating forecasts into policy also requires transparent interpretation. Methods: Surveillance data (2021-2023) comprising 5,909 observations across 44 countries and five WHO regions were processed. Six models (Naive, Linear, Ridge, XGBoost, LightGBM, LSTM) were benchmarked to forecast one-year-ahead resistance rates using prior-year resistance, antibiotic consumption, and related features. MAE, RMSE, and sMAPE were computed with 95% bootstrap confidence intervals for MAE. A local Retrieval-Augmented Generation (RAG) system (Gemma 4) translated forecast findings into policy guidance grounded in WHO documents. Results: XGBoost achieved the best predictive performance (test MAE = 6.13% [95% CI: 5.83-6.44]), an 85.3% error reduction versus the naive baseline (MAE = 41.79%). SHAP analysis identified prior-year resistance as the dominant predictor (50.5% gain). Regional forecast error tracked surveillance coverage, from 3.65% in the European Region to 8.61% in South-East Asia. The RAG pipeline generated source-attributed policy responses without fabricated citations. Conclusion: Short-term AMR resistance rates exhibit strong temporal autocorrelation that can be accurately forecasted using gradient boosting. Coupling these forecasts with a hallucination-resistant RAG system provides a scalable, evidence-based decision-support framework for AMR governance. v3 correction: a leakage audit found feature-construction defects; on the corrected panel a persistence forecast (MAE 5.79) significantly outperforms XGBoost (6.55), and the 85.3% claim is withdrawn (see Correction).