Rapid AMR prediction in Pseudomonas aeruginosa combining MALDI-TOF MS with DNN model

Pseudomonas aeruginosa is a significant clinical pathogen that poses a substantial threat due to its extensive drug resistance. The rapid and precise identification of this resistance is crucial for effective clinical treatment. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used for antibiotic susceptibility differentiation of some bacteria in recent years, the genetic diversity of P. aeruginosa complicates population analysis. Rapid identification of antimicrobial resistance (AMR) in P. aeruginosa based on a large amount of MALDI-TOF-MS data has not yet been reported. In this study, we employed publicly available datasets for P. aeruginosa, which contain data on bacterial resistance and MALDI-TOF-MS spectra. We introduced a deep neural network model, synergized with a strategic sampling approach (SMOTEENN) to construct a predictive framework for AMR of three widely used antibiotics.

The framework achieved area under the curve values of 90%, 85%, and 77% for Tobramycin, Cefepime, and Meropenem, respectively, surpassing conventional classifiers. Notably, random forest algorithm was used to assess the significance of features and post-hoc analysis was conducted on the top 10 features using Cohen's d. This analysis revealed moderate effect sizes (d = 0.5-0.8) in Tobramycin and Cefepime models. Finally, putative AMR biomarkers were identified in this study.

This work presented an AMR prediction tool specifically designed for P. aeruginosa, which offers a hopeful pathway for clinical decision-making.