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Abstract Background Rapid blood culture diagnostics increase cost and have unclear benefit for patients with Gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, prospective randomized controlled trial (RAPIDS-GN), comparing outcomes of patients with GNB BSI who had blood culture testing with standard of care (SOC) culture and antibiotic susceptibility testing (AST) vs. rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (AXDX). Methods Subjects with blood culture Gram stain showing GNB were randomized to receive SOC testing with antimicrobial stewardship review (AS) or AXDX plus SOC testing with AS, at two academic medical centers between October 2017 and October 2018. SOC testing included rapid MALDI-TOF mass spectrometry ID and agar dilution or broth microdilution AST. In a modified intention to treat analysis, subjects were excluded if: Gram stain was erroneous, culture was positive during off-hours, blood culture in the prior week had GNB, they were deceased/on comfort care, or admitted to a nonparticipating hospital. The primary outcome was time to first antibiotic modification within 72 hours after randomization. Subjects without antibiotic modifications were assigned a time of 72 hours. No censoring was observed. T-tests and Wilcoxon rank-sum tests were used for statistical analyses. Results Of 500 randomized subjects, 448 were included (226 SOC, 222 AXDX). Groups did not differ in baseline characteristics (Table 1). Median (IQR) hours to first antibiotic modification was faster in the AXDX vs. SOC group [8.6 (2.6, 27.6) vs. 14.9 (3.3, 41.1)], P = 0.02 (Figure 1). Median (IQR) hours to first Gram-negative antibiotic modification (including escalation and de-escalation) was faster in the AXDX than SOC group [17.4 (4.9, 72) vs. 42.1 (10.1, 72)], P < 0.001 (Figure 2). Groups did not differ in clinical outcomes (Table 2). Mean (S.D.) time to results was faster for AXDX than SOC for organism ID [2.7 (1.2) h vs. 15.6 (20.3) h, P < 0.001] and AST [13 (55.7) h vs. 54.6 (45.5) h, P < 0.001]. Conclusion In the largest trial to evaluate the clinical impact of a blood culture diagnostic for GNB BSI, we found that rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for Gram-negative bacteremia. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursement, editor’s stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents.

Abstract Background Achieving appropriate therapy for BSI caused by Gram-negative rods (GNR) is challenging. The availability of AST results allows de-escalation from broad- to narrow-spectrum agents. De-escalation is a goal of antimicrobial stewardship (AS). Through the analysis of inpatient BL antibiotic regimens in a nationwide cohort of patients with Escherichia coli and Klebsiella pneumoniae BSI, we compared the relative spectrum of empiric and definitive treatments to AST results and identified opportunities for de-escalation. Methods Using a cohort of patients hospitalized within VHA, we identified patients with a blood culture positive for E. coli or K. pneumoniae between 2006 and 2015. We analyzed the subset of patients receiving inpatient BLs before and after Gram stain (GS) and AST results. BLs were grouped into five tiers of increasing spectrum, both with and without a requirement for anaerobic activity (Figure 1). Tiers of BLs across the treatment periods were summarized and compared with the lowest-spectrum tier with an active agent. Rates of inactive, optimal, and overly broad BL therapy were summarized by organism and treatment period. Results Of 36,531 BSI identified, we analyzed a subset of 10,825 (7,100 E. coli, 3,725 K. pneumoniae) that met our inclusion criteria (Figure 2). The use of inactive BL agents decreased across time, falling from 11% in early empiric to 4.5% in definitive treatments. The proportion of patients receiving the narrowest available effective BL therapy (“optimal” therapy) increased from 5% to 8% after GS results and to 14% after AST results (Figure 3). De-escalation to optimal therapy after AST results was observed in only 7% of opportunities. If anaerobic activity was required, a smaller proportion of cases would be considered overtreated in the empiric periods (45–46%), but de-escalation after AST results was observed in only 10% of these cases. Conclusion Changes in BL agents across treatment periods reflect an escalation to active treatment, but the absence of de-escalation after AST results was available. This was true both with and without considering a need for anaerobic activity. Expansion of this analysis to include additional classes such as fluoroquinolones may reveal opportunities for AS and de-escalation to optimal therapy in the treatment of E. coli and K. pneumoniae BSI. Disclosures R. Patel, CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Research grant – monies paid to Mayo Clinic. Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest and Genentech: Consultant and Scientific Advisor, Consulting fee – monies paid to Mayo Clinic. ASM and IDSA: Travel reimbursement and editor’s stipends, Travel reimbursement and editor’s stipends. NBME, Up-to-Date and the Infectious Diseases Board Review Course: Varies, Honoraria. Mayo Clinic: Employee, Salary. R. Banerjee, Accelerate Diagnostics, Biomerieux, BioFire: Grant Investigator, Research grant and Research support.

Escherichia colibacteremia is caused mainly by sequence type complex 131 (STc131) and two clades within its fluoroquinolone-resistance-associatedH30 subclone,H30R1 andH30Rx. We examined clinical and molecular correlates ofE. colibacteremia in two geographically distinct centers.