None listed
Conditions
Brief summary
Inadequate antibiotic therapy is a critical determinant of survival in patients admitted to an Intensive Care Unit (ICU) with overwhelming infection requiring renal replacement therapy (RRT). Guidelines for effective dosing are not available because RRT can be vastly different between ICUs, resulting in significantly different antibiotic pharmacokinetics. Developing an evidence-based antibiotic dosing guideline is of global significance and should be considered a priority to improving clinical outcomes for patients requiring RRT that have infections.
Interventions
One of these study drugs (Piperacillin-Tazobactam, Meropenem, Vancomycin, Imipenem and Lizezolid) will be chosen, administered and dosed as per standard administration guidelines respective to the hospital. Participants will complete a full course of intravenous study drug for approx 7 days or as required by the site doctor to treat the associated infection. Study samples will be taken once on a dosing interval on days 1-2 and then again during a dosing interval between days 3-6. Serial samples
One of these study drugs (Piperacillin-Tazobactam, Meropenem, Vancomycin, Imipenem and Lizezolid) will be chosen, administered and dosed as per standard administration guidelines respective to the hospital. Participants will complete a full course of intravenous study drug for approx 7 days or as required by the site doctor to treat the associated infection. Study samples will be taken once on a dosing interval on days 1-2 and then again during a dosing interval between days 3-6. Serial samples of plasma, effluent and urine collections will be measured over either a 6, 8 or 12 hour study period to describe PK changes and potential resolution of infection as follows (assumes a 30-minute infusion for Meropenem or Piperacillin-Tazobactam and a 60-minute infusion for Vancomycin). Study samples will also be analysed to assess RRT clearance of drugs including sedatives and analgesics as well as micro nutrients (e.g. vitamin c , selenium).
Sponsors
Nartional Health and Medical research Council
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older 2. Acute kidney injury requiring renal replacement therapy (defined according to published RIFLE, AKIN or KDIGO criteria) 3. Clinical indication for IV Piperacillin-Tazobactam, Meropenem or Vancomycin 4. Expected to be on filter for at least 4 days 5. Presence of intra-arterial line for blood sampling if renal replacement therapy filter port sampling not possible 6. Informed consent from patient or patient’s authorized representative
Exclusion criteria
1. Imminent death/not expected to survive etc. 2. Major bleeding or Haemoglobin <70g/L or platelets <20 x103/mm3. 3.Regular dosing with any of the 5 study antibiotics for greater than 36 hours, within the 7 days prior to enrolment 4. Unable to obtain consent
Outcome results
None listed