Ritu Banerjee, MD, PhD
Vanderbilt University Medical Center
Disclosure: Accelerate Diagnostics: Grant/Research Support
BioFire: Research Grant
Biomerieux: Research Grant
Roche: Research Grant
Abinash Virk, MD
Disclosure: Travel and Health Wellness LLC : Other Financial or Material Support, Received payment for lectures on global antimicrobial resistance in the United Arab Emirates, Jordan, and Lebanon in 2017 and has received royalties from Travel and Health Wellness LLC (all funds paid to her institution).
Robin Patel, MD
Disclosure: 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, Next Gen 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
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 10/2017-10/2018. 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 non-participating hospital. 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].
In the largest trial to evaluate 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.