Clinical trial NCT04503252: Probability of Target Attainment With Standard Intermittent Bolus Administration of Cefazolin in Patients With Complicated Infections Caused by Staphylococcus Aureus
Official title: Probability of Target Attainment With Standard Intermittent Bolus Administration of Cefazolin in Patients With Complicated Infections Caused by Staphylococcus Aureus: A Prospective Single-center Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Staphylococcus Aureus Infection
Keywords: Bloodstream infection (BSI)
Minimum inhibitory concentration (MIC)
Methicillin-susceptible S. aureus (MSSA)
Staphylococcus aureus (S. aureus)
β-lactam antibiotics
flucloxacillin
cefazolin
pharmacological target attainment
Torque Teno virus (TTV)
Therapeutic drug monitoring (TDM)
antibiotic sweat concentrations
Complicated S. aureus infection (CSAI)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: propatient foundation Basel
First posted: 2020-08-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Inpatients with CSAI fulfilling the inclusion criteria and admitted at the University Hospital Basel.

Brief summary: Given the paucity of pharmacological data on cefazolin treatment of Methicillin-susceptible S. aureus (MSSA) complicated S. aureus infection (CSAI), the primary purpose of this study is to investigate the probability of pharmacological target attainment (in the blood and infected tissue) with standard intermittent bolus administration of cefazolin in patients with CSAI caused by MSSA by determining plasma concentrations of cefazolin and exact Minimum inhibitory concentration (MICs) of the causative MSSA strains in patients with various disease severities (e.g. critically ill vs. noncritically ill patients).

* Sub-study quantitative measurement of Torque Teno virus (TTV): The primary purpose of this sub-study is to describe the viral kinetics of TTV in CSAI patients and to explore the association of TTV viremia with clinical outcomes and molecular markers of activation of the immune system.
* Sub-study investigating antibiotic concentrations in sweat as a non-invasive therapeutic drug monitoring


Eligibility criteria: Inclusion Criteria:

* CSAI caused by MSSA. CSAI is defined as MSSA BSI with a positive follow-up blood culture result for MSSA or the presence of a site of infection remote from the primary focus caused by hematogenous seeding (e.g. endocarditis, vertebral osteomyelitis) or extension of the infection beyond the primary focus (e.g. septic thrombophlebitis or abscess); or deep-seated infections caused by MSSA (e.g. osteoarticular infections, deepseated abscesses).
* Current or intended treatment with cefazolin

Exclusion Criteria:

* Previous enrolment into the current study within 30 days
* Hemodialysis (patients on hemofiltration are eligible)
* Patients who are very likely to stop treatment with cefazolin 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 in the next 48 hours as per treating physician.
* Outpatients
* Women who are pregnant (special pharmacokinetic)
* Polymicrobial infection except concomitant isolation of a likely contaminant (e.g. Staphylococcus epidermidis or Propionibacterium acnes) or an anaerobic pathogen. If an additional pathogen is identified after inclusion of the patient into the study, the patient will remain in the study.
* Not-complicated S. aureus infections: non-bacteremic skin- and soft tissue or small Joint infections without deep-seated abscesses (as these patients will be quickly switched to oral antibiotics)
* CSAI caused by methicillin-resistant S. aureus (MRSA)

Additional exclusion criteria for the sub-study investigating cefazolin concentrations in sweat:

* Allergic to pilocarpine
* Continuous oxygen therapy without the possibility to interrupt oxygen administration for 10min
* Pacemaker

Primary outcomes:
measure: Trough concentration of cefazolin in plasma samples
timeFrame: 1st (mid-dose and trough sample), 3rd (mid-dose and trough sample),7th and 14th day (for both only trough sample) of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Total plasma concentrations of cefazolin in plasma samples
timeFrame: 1st (mid-dose and trough sample), 3rd (mid-dose and trough sample) of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Free drug concentrations of cefazolin in plasma samples
timeFrame: 1st (mid-dose and trough sample), 3rd (mid-dose and trough sample) of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Trough concentration of cefazolin in sweat samples
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Total sweat concentrations of cefazolin
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Free drug concentrations of cefazolin in sweat samples
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Target attainment (100%fT>MIC)
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
Secondary outcomes:
measure: Pharmacological target attainment (100%fT>MIC) in infected tissue
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Attainment of an accepted threshold for toxicity (100%fT>10xMIC) in blood
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: Level of cefazolin tolerance of the isolated pathogen
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: TTV substudy: quantification of DNA
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
measure: TTV substudy: quantification of cytokines
timeFrame: 1st, 3rd,7th and 14th day of cefazolin treatment (+/-1-5 day) and if applicable in weekly intervals during outpatient parenteral antibiotic treatment (within 4 weeks)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Internal Medicine
Study officials:
affiliation: University Hospital Basel, Division of Internal Medicine
name: Michael Osthoff, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: