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Background We have previously shown that vancomycin-resistant E. faecium (VRE) with DAP MICs close to the breakpoint (4 µg/mL) harbor genetic changes associated with DAP resistance (DAP-R). Further, DAP MIC was a predictor of poor microbiological eradication in patients with VRE bacteremia treated with DAP. Furthermore, DAP-susceptible VRE isolates with DAP MIC of 3–4 µg/mL (Etest) were more likely to fail DAP therapy, independently of the DAP dose used. Here, we used WGS to determine whether mutations associated with DAP-R could predict DAP MICs. Methods We performed WGS to identify potential determinants of DAP-R in 80 E. faecium isolates (62 DAP-S and 18 DAP-R recovered from bloodstream and other infection sites) in diverse US geographical locations. Two modeling strategies were employed with the aim of increasing the robustness of our prediction strategy, (i) a logistic regression model approach to predict the probability of an isolate of exhibiting a DAP MIC of ≥ 3µg/dl based on the presence of relevant mutations, and (ii) a linear regression model to predict a single doubling dilution increase on DAP MIC in the presence or absence of mutations associated with DAP-R, after transforming MICs to a log2 scale. Statistical significance (P value) was set at

– A retrospective review of medical records was performed from 2010-2013 of all VRE faecium bloodstream infections from individual patients at a single 900 bed teaching hospital in Detroit – 166 VRE faecium isolates, collected from 2010-2013, were evaluated – Identification and susceptibility of isolates was performed in the microbiology laboratory using Vitek 2 (bioMerieux, Durham, NC) – Baseline demographics and characteristics, risk factors, and therapeutic antibiotic regimens used were evaluated to assess 90-day all-cause mortality