Genotype-to-Phenotype Agreement of Antimicrobial Resistance in Escherichia coli

Background Most Escherichia coli reside as commensal intestinal microflora without harming human health. But some E. coli strains are pathogenic and can cause deadly infections. Antimicrobial resistant E. coli is associated with more than 1.5 million deaths globally. Here, we studied the prevalence of antimicrobial resistance in E. coli isolates from two cities based on the antimicrobial(AMR) genes and MIC values. By correlating genotypic and phenotypic antimicrobial resistance, we also examined the performance of whole genome sequencing (WGS) based prediction of phenotypic resistance. Methods A total 109 E. coli isolates from Detroit, MI and Cleveland, OH hospitals underwent WGS. Antibiotic susceptibility testing (AST) was performed using the gram-negative AST cards on the VITEK 2 system. WGS was performed with Nextseq 550 using Nextera flex kits. After de novo assembly, AMR genes were identified using AMR gene database, ResFinder. Results The resistance to beta-lactam antibiotics including 1st and 3rd generation cephalosporins were very high among the E. coli isolates. They were susceptible to penicillin combinations and 2nd generation cephalosporins. While resistance to quinolone antibiotics was high, resistance to aminoglycoside, tetracycline, and sulfonamide/trimethoprim were relatively low (Figure 1). As shown in Table 1, WGS-based method accurately predicted the majority of antimicrobial resistance phenotypes with accuracy of 0.89 ∼ 1.0. However, for cephalothin (0.36), piperacillin/tazobactam (0.69), and amikacin (0.63), the prediction accuracy was low which could potentially lead to false predictions of antimicrobial resistance. Extended Spectrum Beta-Lactamase (ESBL) genes such as blaCTX-M, blaOXA, and blaTEM were abundant, though subtle difference in the prevalence of AMR genes between two cities was observed (Figure 2).Figure 1.The prevalence of antimicrobial resistance to various antibiotics in E. coli isolates from Detroit, MI and Cleveland, OH.Figure 2.Prevalence of WGS identified AMR genes associated with antibiotics drugs. Conclusion Most of the E. coli isolates contained various ESBL genes and their gyrA genes were mutated to quinolone resistant forms. Therefore, most of the isolates were resistant to many beta-lactam and quinolone drugs. WGS based prediction of phenotypic resistance showed good predictive values but needs more studies to increase sensitivity and specificity. Disclosures Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria