Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

• Reveal (Diagnostic test): Reveal is a rapid AST method, which uses small molecule sensor technology to detect growth of bacterial populations by measuring volatile metabolites, and provides AST results in \~5 hours. Reveal™ is approved for clinical use in the European Union (EU) and Israel and approval is in process in India, and provides minimum inhibitory concentrations (MICs) for 28 antibiotics and 9 Gram negative species, that together account for \~90% of organisms causing Gram negative blood stream infections (BSI).

Primary outcomes

• Participant Clinical Outcomes, as Measured by Desirability of Outcome Ranking (DOOR) [Up to 30 days after Gram stain result]: The composite 3-category DOOR outcome will assess three deleterious events (unsuccessful discharge, lack of clinical response, and undesirable events) in addition to survival up to 30 days after Gram stain result. The primary DOOR outcome measure is defined using three ordered levels. From best to worst, they are: 1. Alive without deleterious events 2. Alive with at least 1 deleterious event 3. Death

Secondary outcomes

• Number of Participants With All-Cause Mortality [Up to 30 days post Gram Stain]: All-cause in-hospital mortality up to 30 days post Gram stain result
• Hospital Stay Length [up to 30 days post Gram stain result]: Length of index stay in the hospital up to 30 days post Gram stain result, for those subjects alive at 30 days. Length of stay will be calculated as date of discharge minus date of Gram stain result.
• Number of Participants With ICU Admissions [up to 30 days post Gram stain result]: ICU admission up to 30 days post Gram stain result
• Number of Participants With New Acquisition of Multi-Drug Resistant Organism (MDRO) and/or C. Difficile [up to 30 days post Gram stain result]: New acquisition is defined as detection of MDRO/C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months. MDRO will be identified on routine clinical or surveillance samples using local laboratory diagnostic procedures and include: Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus species 3rd generation cephalosporin-non-susceptible Enterobacterales Carbapenem-resistant Enterobacterales, as defined by the Center for Disease Control and Prevention: resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate produces a carbapenemase Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems) Carbapenem-resistant Acinetobacter species Candida auris
• Number of Participants With New Multidrug-Resistant Organism (MDRO) [up to 30 days post Gram stain result]: MDRO will be identified on routine clinical or surveillance samples using local laboratory diagnostic procedures and include: Methicillin-resistant Staphylococcus aureus Vancomycin-resistant Enterococcus species 3rd generation cephalosporin-non-susceptible Enterobacterales Carbapenem-resistant Enterobacterales, as defined by the Center for Disease Control and Prevention: resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate produces a carbapenemase Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems) Carbapenem-resistant Acinetobacter species Candida auris
• Number of Participants With C. Difficile [up to 30 days post Gram stain result]: Detection of C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months.
• Number of Participants With MRSA [up to 30 days post Gram stain result]: Detection of Methicillin-resistant Staphylococcus aureus (MRSA)
• Number of Participants With VRE [up to 30 days post Gram stain result]: Detection of Vancomycin-resistant Enterococcus species (VRE)
• Number of Participants With CTX Resistant Enterobacterales [up to 30 days post Gram stain result]: Detection of 3rd generation cephalosporin-non-susceptible Enterobacterales (CTX resistant Enterobacterales)
• Number of Participants With CRE [up to 30 days post Gram stain result]: Detection of Carbapenem-resistant Enterobacterales (CRE)
• Number of Participants With MDR Pseudomonas [up to 30 days post Gram stain result]: Detection of Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (MDR Pseudomonas)
• Number of Participants With CRAb [up to 30 days post Gram stain result]: Detection of Carbapenem-resistant Acinetobacter species (CRAb)
• Number of Participants With Candida Auris [up to 30 days post Gram stain result]: Detection of Candida auris using local laboratory diagnostic precedures
• Time to Effective Antibiotic Therapy [within 3 days from Gram stain result]: Time to effective antibiotic therapy within 3 days from Gram stain result, defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST.
• Receiving Effective Antibiotic Therapy Within 24 Hours [within 24 hours from Gram stain result]: Effective antibiotic therapy was defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST and to which the isolate was not intrinsically resistant.
• Receiving Effective Antibiotic Therapy Within 3 Days [within 3 days from Gram stain result]: Effective antibiotic therapy was defined as treatment with an antibiotic (or antibiotic class) to which the blood isolate is susceptible based on standard of care (SOC) AST and to which the isolate was not intrinsically resistant.
• Time to Antibiotic Escalation or De-escalation [within 3 days from Gram stain result]: Time to antibiotic escalation or de-escalation of Gram negative coverage in those who have antibiotic change within 3 days from Gram stain result. Escalation: Changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral (PO) to intravenous (IV) route. De-escalation: Changing to a narrower spectrum antibiotic , cessation of one or more antibiotics, or changing from an IV to PO route of appropriate drug (i.e. IV to PO ciprofloxacin or levofloxacin).
• Antibiotic Change Within 3 Days [within 3 days from Gram stain result]: Antibiotic changes for Gram-negative coverage within 3 days from Gram stain result. Among as-randomized population, the antibiotic utilization can be categorized as follow: (a) first change is escalation, (b) first change is de-escalation, (c) no change, and (d) no Gram-negative antibiotic received within 3 days.

Sex: All

Inclusion Criteria:

1. Positive blood culture with Gram stain showing GNB.
2. Hospitalized at the time of Gram stain result.
3. Enrolled within 16 hours of blood culture positivity.

Exclusion Criteria:

1. Positive blood culture for GNB within the prior 7 days (if known at the time of Gram stain result).
2. Deceased at the time of Gram stain result.
3. Gram-positive bacilli, Gram-positive cocci, Gram-negative cocci, yeast, fungi, or multiple morphologies of GNB detected on Gram stain of blood culture.
4. Previous enrollment in this study.

Participant flow

Outcome results

• Participant Clinical Outcomes, as Measured by Desirability of Outcome Ranking (DOOR) (Primary), Count of participants, Participants: Reveal 196; Standard of Care 216 (p 0.527)
• Number of Participants With All-Cause Mortality (Secondary), Count of participants, Participants: Reveal 100; Standard of Care 99 (p 0.592)
• Hospital Stay Length (Secondary), Median, Days: Reveal 8 (7 to 8); Standard of Care 8 (7 to 9) (p 0.099)
• Number of Participants With ICU Admissions (Secondary), Count of participants, Participants: Reveal 14; Standard of Care 16 (p 0.83)
• Number of Participants With New Acquisition of Multi-Drug Resistant Organism (MDRO) and/or C. Difficile (Secondary), Count of participants, Participants: Reveal 60; Standard of Care 61 (p 0.812)
• Number of Participants With New Multidrug-Resistant Organism (MDRO) (Secondary), Count of participants, Participants: Reveal 55; Standard of Care 51 (p 0.468)
• Number of Participants With C. Difficile (Secondary), Count of participants, Participants: Reveal 9; Standard of Care 16 (p 0.201)
• Number of Participants With MRSA (Secondary), Count of participants, Participants: Reveal 2; Standard of Care 1 (p 0.53)
• Number of Participants With VRE (Secondary), Count of participants, Participants: Reveal 23; Standard of Care 20 (p 0.509)
• Number of Participants With CTX Resistant Enterobacterales (Secondary), Count of participants, Participants: Reveal 11; Standard of Care 5 (p 0.103)
• Number of Participants With CRE (Secondary), Count of participants, Participants: Reveal 21; Standard of Care 20 (p 0.730)
• Number of Participants With MDR Pseudomonas (Secondary), Count of participants, Participants: Reveal 8; Standard of Care 4 (p 0.207)
• Number of Participants With CRAb (Secondary), Count of participants, Participants: Reveal 14; Standard of Care 10 (p 0.333)
• Number of Participants With Candida Auris (Secondary), Count of participants, Participants: Reveal 10; Standard of Care 6 (p 0.261)
• Time to Effective Antibiotic Therapy (Secondary), Median, Hours: Reveal 0 (0 to 10); Standard of Care 0 (0 to 23) (p 0.176)
• Receiving Effective Antibiotic Therapy Within 24 Hours (Secondary), Count of participants, Participants: Reveal 345; Standard of Care 329 (p 0.003)
• Receiving Effective Antibiotic Therapy Within 3 Days (Secondary), Count of participants, Participants: Reveal 365; Standard of Care 374 (p 0.227)
• Time to Antibiotic Escalation or De-escalation (Secondary), Median, Hours: Reveal 22 (14 to 25); Standard of Care 36 (30 to 45) (p <0.0001)
• Antibiotic Change Within 3 Days (Secondary), Count of participants, Participants: Reveal 92; Standard of Care 135 (p 0.044)

Adverse events

Time frame: From enrollment through 30 days

• Results publication: Banerjee R, Komarow L, Li Y, Mau D, Dodd A, Geres H, Greenwood-Quaintance K, Adler A, Baliga S, Chowers M, Chrysos G, Zarkotou O, Paul M, Pournaras S, Regueiro DS, Evans S, Chambers H, Fowler VG Jr, Patel R; Antibacterial Resistance Leadership Group. Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia: The FAST Randomized Clinical Trial. JAMA. 2026 May 26;335(20):1762-1773. doi: 10.1001/jama.2026.5487. PMID 41999287
• Results publication: Banerjee R, Komarow L, Li Y, Wu Q, Sanchez-Gonzalez L, Mau D, Abbenante E, Schwager N, Dodd A, Souli M, Geres HS, Doernberg S, Greenwood-Quaintance K, Evans SR, Chambers HF, Fowler VG Jr, Patel R; Antibacterial Resistance Leadership Group. Study protocol for a multicenter, multinational prospective randomized controlled trial comparing outcomes in subjects with Gram-negative bacteremia who have blood culture evaluation using Fast Antibiotic Susceptibility Testing vs. standard of care testing: the FAST trial. Trials. 2025 Nov 12;26(1):500. doi: 10.1186/s13063-025-09228-4. PMID 41225518

• Study Protocol (PDF, 2024-04-11)
• Statistical Analysis Plan (PDF, 2025-05-20)
• Informed Consent Form (PDF, 2022-06-22)

• Ritu Banerjee, MD, PhD, Principal investigator, Vanderbilt University Medical Center
• Vance Fowler, MD, Study director, Duke Clinical Research Institute

NIH grants: UM1AI104681