198. The correlation of the genetic antibiotic resistance markers to antibiotic susceptibility testing (AST)

Abstract

Abstract Background Antibiotic resistant infections are a risk for increased patient mortality due to long time-to-results for current diagnostic methods. Results from a ∼1,500 patient trial demonstrated bacterial blood culture required 51 hours on average for a positive result. Current antibiotic susceptibility testing (AST) requires two additional days for phenotypic results. Studies show delays in effective treatment increases mortality rates by 7.6% every hour. The CDC classifies carbapenem-resistant Enterobacterales (13,000 annual deaths) as urgent threats, and vancomycin-resistant Enterococci and methicillin-resistant S. aureus (∼15,000 annual deaths combined) as serious threats. Identifying resistance markers direct from patient samples may aid clinical decisions, reduce antibiotic use, reduce time to effective therapy, and improve patient outcomes Methods 200 antibiotic resistant bacterial strains were genotyped for 13 clinically-relevant resistance genes and screened for antibiotic resistance phenotypes. Results identified correlations between resistance markers and phenotypic resistance and potential aid for clinical treatment. Results High resistance to vancomycin and piperacillin-tazobactam, first-line antibiotics, were seen in 48 Gram-positive and 69 Gram-negative strains. Presence of Gram-positive markers vanA or vanB correlated to 100% (28/28) vancomycin resistance and 88% (25/28) ampicillin resistance. In 85 sequenced Gram-negative strains, 35 harbored metallo-β-lactamase (blaIMP,blaNDM,blaVIM), 35 contained extended spectrum β-lactamase (blaCTX-M-14,blaCTX-M-15), 21 contained AmpC β-lactamase (blaDHA,blaCMY), and 34 contained carbapenenase (blaKPC,blaOXA48). These markers correlated to 100% resistance to ampicillin, cefazolin, and cefuroxime in all strains. Conclusion Together, these data suggest that molecular diagnostics that identify genetic markers may provide clinicians with needed information during a window when therapeutic intervention can improve patient outcomes. Disclosures Caitlin Morrison, B.S., T2 Biosystems: Stocks/Bonds Janis Pham, B.S., T2 Biosystems: Stocks/Bonds Alicyn Pearson, PhD, T2 Biosystems: Stocks/Bonds John King, B.S., T2 Biosystems: Stocks/Bonds Heather S. Lapp Noucas, MSc, T2 Biosystems: Stocks/Bonds Robert Shivers, PhD, T2 Biosystems: US20200291488A1|T2 Biosystems: Stocks/Bonds Roger Smith, Ph.D., T2 Biosystems, Inc: US20180188195A1, EP3849938A1,WO2020257691A1, WO2020252084A1|T2 Biosystems, Inc: Stocks/Bonds.