Trial Outcomes & Findings for Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial (NCT NCT06174649)

Fast Antibiotic Susceptibility Testing for Gram Negative Bacteremia Trial

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

All-cause in-hospital mortality 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.

ICU admission 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

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

Detection of C. difficile in subjects who do not have preceding clinical or surveillance cultures with these organisms in the prior 3 months.

Detection of Methicillin-resistant Staphylococcus aureus (MRSA)

Detection of Vancomycin-resistant Enterococcus species (VRE)

Detection of 3rd generation cephalosporin-non-susceptible Enterobacterales (CTX resistant Enterobacterales)

Detection of Carbapenem-resistant Enterobacterales (CRE)

Detection of Pseudomonas aeruginosa resistant to carbapenems/multi-drug resistant (MDR Pseudomonas)

Detection of Carbapenem-resistant Acinetobacter species (CRAb)

Detection of Candida auris using local laboratory diagnostic precedures

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.

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.

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 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 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.