A Platform Trial for Gram Negative Bloodstream Infections

PLATFORM INCLUSION CRITERIA Platform Inclusion Criteria: * admitted to a participating hospital * positive blood culture with Gram negative (GN) bacterium Platform Exclusion Criteria: * patient's goals of care are for palliation with no active treatment * moribund patient, not expected to survive \> 72 hours * previously enrolled in the platform trial * not eligible for any domain at the time of screening DOMAIN SPECIFIC INCLUSION AND EXCLUSION CRITERIA 1. De-escalation versus no de-escalation domain Inclusion Criteria \- included in BALANCE+ platform Exclusion Criteria * receiving an empiric antibiotic regimen at the time of blood culture finalization to which the GN pathogen(s) are not sensitive * arbapenem-non-susceptible * no de-escalation option due to any or all of: * antimicrobial resistance * allergies * medical contraindications * drug-drug interaction risk * other relevant reason * patients with a suspected or proven polymicrobial source of infection * \> 24 hours since index blood culture susceptibility results finalization 2. Beta-lactam versus non-beta-lactam oral/enteral treatment domain Inclusion Criteria * included in BALANCE+ platform * initially treated with intravenous antibiotics, but clinical team transitioning patient to oral/enteral antibiotic within 7 days of starting treatment Exclusion Criteria * enrolled in an arm of another BALANCE+ platform domain which limits the use of oral/enteral therapy: * no-de-escalation arm (patients in the no de-escalation arm cannot be randomized into this domain unless they are ready for discharge home, in which case de-escalation is allowable to oral agents at discharge) * no non-beta-lactam options due to any or all of: * resistance * allergies * medical contraindications * drug-interaction risk * other relevant reason * no beta-lactam options due to any or all of: * resistance * allergies * medical contraindications * drug-interaction risk * other relevant reason * pregnancy * already received \>24 hours of oral antibiotics after index blood culture finalization 3. Central vascular catheter replacement domain Inclusion Criteria * included in BALANCE+ platform * has an indwelling central vascular catheter that was already in place within the 48-hour period before the onset of bloodstream infection (i.e. is not a new catheter placed within 48 hours of the onset of infection) Exclusion Criteria * patient has no ongoing need for a central vascular catheter * patient has definite indication for central vascular catheter removal * ongoing septic shock with definite/probable line source * concomitant S. aureus bacteremia * concomitant candidemia * local suppurative signs (severe redness, warmth, pain, swelling or fluctuance/collection) necessitating catheter removal, or other clinical evidence of infected line (e.g. imaging/echocardiographic findings) 4. Low-risk AmpC domain Inclusion Criteria * included in BALANCE+ platform * positive blood culture with GN bacterium, of the following species: i. Serratia spp. ii Morganella spp. iii Providencia spp. iv Proteus spp. other than P.mirabilis * organism is susceptible to ceftriaxone Exclusion Criteria * severe allergy to beta-lactams (e.g., type 4 hypersensitivity reaction or DRESS) * baseline phenotypic non-susceptiblity to ceftriaxone * more than 1 calendar day beyond availability of susceptibility results 5. Follow up blood culture domain Inclusion Criteria \- included in BALANCE+ platform Exclusion Criteria * patient died or discharged from hospital prior to day 4 * blood culture already collected by the treating team at day 4±1 * \>5 days since index positive blood culture collection * definite indication for repeat blood culture testing * concomitant S. aureus bacteremia * concomitant Candidemia * clinical suspicion for infective endocarditis