Abstract
Background
Appropriate antibiotic (Ab) therapy of bloodstream infections (BSI) is often delayed by time to blood culture (BC) positivity, species (sp) identification and Ab sensitivity (sensi). The T2Resistance (T2R) Panel is a direct-from-blood (culture-independent) diagnostic that detects 13 genetic markers associated with methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), ESBL- and carbapenemase-producing Enterobacteriaceae (E). We assessed T2R performance in detecting these resistant bacteria in whole blood (WB) and analyzed possible impact on time to appropriate Ab.
Methods
We performed T2R using WB samples obtained from patients (pts) on the same day as BCs from July 2019-2020. Receipt of appropriate Ab was assessed at time of empiric, Gram stain-directed, MALDI-directed (sp identification) and sensi-directed therapy. T2R results were not available to care teams. Teams were notified of positive BCs. Stewardship optimized Abs based on sensi.
Results
BC from 103 pts grew 114 bacterial sp: E (n=54; 16 ESBL-, 1 KPC-producer), S. aureus (n=29, 22 MRSA), Enterococcus (n=21, 16 VRE), P. aeruginosa and others (n=10). 12 ESBL-E produced CTX-M 14/15. T2R sensitivity and specificity was 78% and 99%, respectively, compared to sequencing of resistance markers. Sensitivity was excellent for vanA/B, KPC (100% each), and CTX-M14/15 (92%); sensitivity was 58% for mecA/C. T2R detected resistance determinants in 3-7h. Median time to appropriate Ab was 16.3h, which was significantly longer for VRE (25.6h) and ESBL- or KPC-E (50.9h) BSIs than for T2R marker-negative bacteria (6.7h; p=0.04). Pts with VRE or ESBL-/KPC-E BSI were less likely to received appropriate empiric Ab (18% and 30%, respectively) than pts with T2R marker-negative BSI (63%; p=0.02; Fig.1). Median times to achieve ≥80% appropriate Ab therapy of marker-negative, VRE and CTX-M/KPC-E BSIs were 15.5h (after Gram stain), 43.9h (after MALDI) and 63.5h (after sensi), respectively.
Antibiotic Therapy
Conclusion
There was a significant delay in appropriate Ab therapy of BSIs, especially in pts infected with VRE and ESBL/KPC-E. T2R rapidly and accurately detected BSI caused by VRE and ESBL/KPC-E, and has the potential to significantly shorten time to appropriate Ab.
Disclosures
Cornelius J. Clancy, MD, Merck (Grant/Research Support) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)