A Platform Trial for Gram Negative Bloodstream Infections

Participation Requirements

• Sex:

  ALL

• Eligible Ages:

  0 and up

Participation Criteria

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