Oral Abstract Submission
Samuel L. Aitken, PharmD, MPH, BCIDP
Clinical Pharmacy Specialist - Infectious Diseases
The University of Texas MD Anderson Cancer Center
Disclosure: Melinta Therapeutoics: Grant/Research Support, Research Grant
Merck, Sharpe, and Dohme: Advisory Board
Shionogi: Advisory Board
Background : Multidrug-resistant (MDR) P. aeruginosa (PA) infections continue to cause significant morbidity and mortality in various patient groups including those with malignancies. Predicting antimicrobial resistance (AMR) from whole genome sequencing data if done rapidly, could aid in providing optimal care to patients.
Methods : To better understand the connections between DNA variation and phenotypic AMR in PA, we developed a new algorithm, variant mapping and prediction of antibiotic resistance (VAMPr), to build association and machine learning prediction models of AMR based on publicly available whole genome sequencing and antibiotic susceptibility testing (AST) data. A validation cohort of contemporary PA bloodstream isolates were sequenced and AST was performed. Accuracy of predicting AMR for various PA-drug combinations was calculated.
Results : VAMPr was built from 3,393 bacterial isolates (83 PA isolates included) from 9 species that contained AST data for 29 antibiotics. 14,615 variant genotypes were identified within the dataset and 93 association and prediction models were built. 120 PA bloodstream isolates from cancer patients were included for analysis in the validation cohort. ~15% of isolates were carbapenem resistant and ~20% were quinolone resistant. For drug-isolate combinations where > 100 isolates were available, machine-learning prediction accuracies ranged from 75.6% (PA and ceftazidime; 90/119 correctly predicted) to 98.1% (PA and amikacin; 105/107 correctly predicted). Machine learning accurately identified known variants that strongly predicted resistance to various antibiotic classes. Examples included specific gyrAmutations (T83I; p < 0.00001)and quinolone resistance.
Conclusion : Machine learning predicted AMR in P. aeruginosaacross a number of antibiotics with high accuracy. Given the genomic heterogeneity of PA, increased genomic data for this pathogen will aid in further improving prediction accuracy across all antibiotic classes.