Core Genome Multilocus Sequence Typing and Antibiotic Susceptibility Prediction from Whole-Genome Sequence Data of...

Over the past decade, whole-genome sequencing (WGS) has overtaken traditional bacterial typing methods for studies of genetic relatedness. Further, WGS data generated during epidemiologic studies can be used in other clinically relevant bioinformatic applications, such as antibiotic resistance prediction. Using commercially available software tools, the relatedness of 38 clinical isolates of multidrug-resistant Pseudomonas aeruginosa was defined by two core genome multilocus sequence typing (cgMLST) methods, and the WGS data of each isolate was analyzed to predict antibiotic susceptibility to nine antibacterial agents. The WGS typing and resistance prediction data were compared with pulsed-field gel electrophoresis (PFGE) and phenotypic antibiotic susceptibility results, respectively. Simpson's Diversity Index and adjusted Wallace pairwise assessments of the three typing methods showed nearly identical discriminatory power. Antibiotic resistance prediction using a trained analytical pipeline examined 342 bacterial-drug combinations with an overall categorical agreement of 92.4% and very major, major, and minor error rates of 3.6, 4.1, and 4.1%, respectively. IMPORTANCE Multidrug-resistant Pseudomonas aeruginosa isolates are a serious public health concern due to their resistance to nearly all or all of the available antibiotics, including carbapenems. Utilizing molecular approaches in conjunction with antibiotic susceptibility prediction software warrants investigation for use in the clinical laboratory workflow. These molecular tools coupled with antibiotic resistance prediction tools offer the opportunity to overcome the extended turnaround time and technical challenges of phenotypic susceptibility testing.