None listed
Conditions
Brief summary
The primary purpose of the study is to estimate the impact on time to effective therapy of real-time pathogen sequencing direct from clinical samples when integrated with personalised antimicrobial dosing in children and adults on ICU with sepsis. It is hypothesised that real-time pathogen sequencing combined with dosing software to identify optimised personalised antimicrobial therapy will reduce the time to effective antimicrobial concentrations in critically ill patients with sepsis leading to improved patient outcomes. This novel approach to rapid pathogen sequencing coupled with antimicrobial dosing software has great potential to overcome the limitations of conventional sepsis diagnostics which often result in prolonged inappropriate antimicrobial therapy. This pilot study will yield key feasibility data to inform future studies which are urgently needed in the era of increasing antimicrobial resistance. Reduced time to optimal antimicrobial therapy may reduce sepsis mortality and ICU length of stay.
Interventions
Design and setting:
The DIRECT study is a pilot prospective, non-randomised multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU.
Participants and interventions:
DIRECT will collect microbiological and pharmacokinetic samples from approximately 50 children and adults with sepsis admitted to one of four ICUs in Brisbane. Consecutive patient
Design and setting: The DIRECT study is a pilot prospective, non-randomised multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU. Participants and interventions: DIRECT will collect microbiological and pharmacokinetic samples from approximately 50 children and adults with sepsis admitted to one of four ICUs in Brisbane. Consecutive patients with suspected sepsis (irrespective of culture results) will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing. Intervention description: Consecutive patients with suspected sepsis admitted to ICU will undergo MinION nanopore pathogen sequencing integrated with personalised antibiotic therapy using a combination of Bayesian dosing software (ID-ODSTM) and measured antibiotic plasma concentrations. A senior ICU pharmacist/clinician at each site will lead this software-guided intervention of antimicrobial dose optimisation. All dosing regimens will be checked by both the senior ICU pharmacist and attending ICU consultant prior to prescription. The final decision regarding the use of the optimised dosing of antibiotics will remain at the discretion of the attending ICU consultant. Participants will be asked to provide the following blood samples. At the time of the suspected sepsis diagnosis, participants will provide a single additional EDTA blood sample. The volume of EDTA blood required is 1-2ml for infants and young children (<5y), 2-6ml for older children (5-12y), and 6–10ml for adolescents and adults. Participants will subsequently provide up to four plasma samples to measure antimicrobial levels at 24h, 48h, 72h, 96h after sepsis diagnosis. The volume of plasma samples required is 0.5ml for infants and young children (<5y), 1-2ml for older children (5-12y), and 3-5ml for adolescents and adults. The duration of patient participation in the study will be up to 5 days. Antimicrobial pharmacokinetic sampling will cease if the patient is discharged from ICU before 5 days.
Sponsors
The University of Queensland
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Admitted to paediatric or adult ICU at one of the participating centres 2. Decision to treat for suspected sepsis, defined as suspected or proven infection with suspected or proven organ dysfunction. 3. Commenced within 24h on intravenous broad-spectrum antibiotics, or within 24h of a change to new antibiotics consistent with treatment for a new episode of suspected sepsis. 4. Blood cultures are being obtained or were obtained within the past 12 hours
Exclusion criteria
1. Inability to gain informed consent during the study period 2. Neonates 3. Death is likely imminent 4. Palliative care patient
Outcome results
None listed