The goal of this clinical trial is to propose a seamless intervention linking rapid bacterial isolate identification and antibiotic resistance gene detection and targeted antibiotic prescription to minimise time between infection onset and appropriate treatment in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales infections. This is an investigator initiated trial.
The primary hypothesis is that these interventions will lead to improved clinical outcomes amongst patients with hospital-acquired bloodstream infection, hospital-acquired pneumonia or ventilator-associated pneumonia due to carbapenem non-susceptible Pseudomonas aeruginosa or Enterobacterales, compared to standard antibiotic susceptibility testing.
Patients will be randomised to either a control or intervention arm. Patients randomised to the intervention arm will have relevant specimens analysed by rapid microbiological diagnostics and will have early availability of ceftazidime-avibactam if appropriate. Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics. Antibiotics will be available to these patients as per usual institutional practice.
patient developed clinical symptoms compatible with bloodstream infection, hospital-acquired or ventilator-associated pneumonia (hospital-acquired and ventilator-associated pneumonia should fulfil US CDC NHSN criteria) AND,
an appropriate specimen has been received by the participating laboratory - that is, a blood culture bottle showing Gram negative bacilli or a respiratory sample collected for clinical purposes showing Gram negative bacilli on Gram stain;
Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR,
where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR,
treatment is not with the intent to cure the infection; OR,
patient is incarcerated in a correctional facility; OR,
Parallel
Rapid Diagnostics
Diagnostic testPatients randomised to the intervention arm, will have the BioFire Blood Culture Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray Pneumonia plus PanelPneumonia Panel or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used. Antibiotic guidelines will be provided to clinicians to aid interpretation of test results and treatment prescription. Ceftazidime-avibactam will be available for targeted use in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales.
Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 post index culture
Patient has died within 14 days from collection of index microbiology culture from any cause or SOFA score has not improved at Day 14 compared with baseline score on day of collection of index microbiology culture
Clinical response
Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee
All-cause mortality
All-cause mortality at Day 14, Day 28, and Day 60 post index culture
Functional outcome
Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture
Composite outcome
Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample
Genomics studies
Genotype of the infection causing bacterial isolate, as available through whole genome sequencing
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