None listed
Conditions
Brief summary
The aim of this study is to evaluate a dose optimisation strategy to improve exposure of beta-lactam antibiotics in haematology/oncology patients with febrile neutropenia. Who is it for? You may be eligible to join this study if you are aged 18 years or above and have a diagnosis of febrile neutropenia and cancer/haematological malignancy, for which you have been prescribed to receive beta-lactam antibiotics. Study details Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will continue to receive standard dosing of beta-lactam antibiotics at the discretion of their treating clinician. Participants in the other group will have their beta-lactam antibiotics dosed according to a new dose optimisation strategy guided by measurements of antibiotic concentration in the blood. All participants will be regularly monitored to determine how well the antibiotic dosing target is met and how long it takes for their fever to subside. It is hoped that the new dose optimisation strategy will help avoid the likelihood of inadequate antibiotic exposure, thereby improving treatment of infections and reducing antibiotic resistance.
Interventions
Initially all patients will receive standard starting doses of beta-lactam antibiotics (e.g 4.5g piperacillin-tazobactam every 8-hourly, 2g cefepime every 8-hourly, 1g meropenem every 8 hourly) via intermittent intravenous infusion. For the intervention group, the unbound (free) concentrations of beta-lactam antibiotics will be calculated from the total concentration assay of blood samples taken at the mid of dosing interval and 15 minutes before the next dose as a trough. Based on the free anti
Initially all patients will receive standard starting doses of beta-lactam antibiotics (e.g 4.5g piperacillin-tazobactam every 8-hourly, 2g cefepime every 8-hourly, 1g meropenem every 8 hourly) via intermittent intravenous infusion. For the intervention group, the unbound (free) concentrations of beta-lactam antibiotics will be calculated from the total concentration assay of blood samples taken at the mid of dosing interval and 15 minutes before the next dose as a trough. Based on the free antibiotic concentration at the specified blood sampling times, whether pharmacokinetic/pharmacodynamic (PK/PD) target is achieved or not will be determined. The PK/PD target is achievement of 100%fT>MIC (the free antibiotic concentration remains above the MIC for the entire duration of the dosing interval). This will be determined by using local institutional antibiograms at the study hospital or European Committee on Antimicrobial Susceptibility Testing (EUCAST) (http://www.eucast.org/clinical breakpoints) recommendations will be used as reference bacterial susceptibility breakpoints. The proposed sampling time allows determination of PK/PD target without calculating the exact time above MIC. Results of the free antibiotic blood concentration and target attainment will be communicated to clinicians treating the patient. Based on the results, investigators of the study will then identify the need for dose adjustment in conjunction with the clinicians. When deemed necessary, dose adjustment will be performed. Doses will be adjusted as necessary either by increasing the frequency by 25 to 50% or changing the mode of administration into extended infusion or both. If trough concentrations are greater than ten times the MIC, dose reduction will be performed by reducing the frequency by 25 to 50 % or decreasing the dose by 50%. The overall duration of treatment will be at clinician discretion. Adherence to the interventional dosing changes was monitored using the drug administration charts which describe the details of drug administration which are signed by and confirmed by nursing staff.
Sponsors
Therapeutics Research Centre, University of South Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
diagnosis of febrile neutropenia, diagnosis of cancer or hematological malignancy, prescribed to receive a beta-lactam antibiotics, ability to get prior informed consent
Exclusion criteria
know or suspected allergy to the study antibiotics, pregnancy, inability to get informed consent
Outcome results
None listed