Target Attainment of Continuous Infusion Flucloxacillin and Cefazolin Coupled With TDM vs. Standard of Care Treatment in Patients With Complicated S. Aureus Infection (TARGET III)
Complicated Staphylococcus Aureus (S. Aureus) Infections (CSAI)
About this trial
This is an interventional treatment trial for Complicated Staphylococcus Aureus (S. Aureus) Infections (CSAI) focused on measuring Therapeutic drug monitoring (TDM), Flucloxacillin (FLU), Cefazolin (CZO), β-lactam antibiotics, antibiotic plasma concentration, standard intermittent bolus administration, continuous infusion, Staphylococcus aureus
Eligibility Criteria
Inclusion Criteria: Informed Consent as documented by signature. For patients, who are not able to sign consent, a physician not involved in the current study has to confirm that patient's interest and rights are guaranteed during participation in the current study. Subsequently, informed consent will be obtained as soon as possible from the patient or his/her legally authorised representative. Age ≥ 18 years CSAI which is defined as (i) blood stream infection (BSI) with S. aureus or (ii) deep-seated infections caused by S. aureus (e.g. osteoarticular infections, deep-seated abscesses) without BSI. Intended or active (less than 24 hours) treatment with FLU or CZO Exclusion Criteria: Patients on hemodialysis or eGFR<10 ml/min as these patients have a special pharmacokinetic Patients on Cytosorb® therapy Patients with liver cirrhosis CHILD B and C Patients who are very likely to stop treatment with FLU or CZO in the next 48 hours as per treating physician (because of treatment failure, switch to oral medication, palliative care, allergy etc.) or who are very likely to be discharged or transferred to another hospital in the next 48 hours as per treating physician. Polymicrobial infection except concomitant isolation of a likely contaminant (e.g. Staphylococcus epidermidis or Cutibacterium acnes). If an additional pathogen is identified after inclusion of the patient into the study, the patient will remain in the study. CSAI caused by methicillin-resistant S. aureus (MRSA) Participation in another study with investigational drug within the 30 days preceding and during the present study Previous enrolment into the current study Any uncontrolled or significant concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements at the discretion of the investigator
Sites / Locations
- University Hospital Basel, Division of Internal Medicine
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
intervention group
control group
Subjects randomized into the intervention group will receive FLU or CZO respectively as continuous infusion as soon as targeted S. aureus treatment is initiated (+24h). The choice of antibiotic is determined by the treating physician in accordance to the recommendations of the infectious diseases (ID) specialists. The loading dose and dose adjustments of FLU and CZO will be determined by the use of a pharmacokinetic modelling application. The maximum daily dose will not exceed the daily licensed dose according to the Summary of Product Characteristics (SmPC).
Subjects randomized to the control group will receive standard of care intermittent bolus infusion FLU or CZO dosed according to the recommendations of the ID specialist and treating physician. Drug concentration will be analysed directly, but the results will not be communicated to the study team or a physician involved in the treatment of the patient. No TDM-guided dose adjustment will be performed in the control group.