Probability of Target Attainment With Standard Intermittent Bolus Administration of Cefazolin in Patients With Complicated Infections Caused by Staphylococcus Aureus

University Hospital, Basel, Switzerland50 enrolled

Overview

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

Study Type

OBSERVATIONAL

Enrollment

Conditions

Staphylococcus Aureus Infection

Interventions

Blood samples for the measurement of the concentration of cefazolin

Blood samples for the measurement of the concentration of cefazolin will be collected on the 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 (usually within 4 weeks after inclusion; only in patients on outpatient continuous parenteral antibiotic treatment).

Sub-study investigating cefazolin concentrations in sweatOTHER

For each visit of included patients, a sweat sample will be collected via a CE certified Macroduct Sweat Collector. Eccrine sweat glands of the lower forearms are stimulated by pilocarpine (a parasympathomimetic) as well as a local current for 5min. Sweat is subsequently collected by capillary containers during 30min and transferred to small tubes on dry ice. Sweat sample analysis is conducted using mass spectrometry.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Trough concentration of cefazolin in plasma samples

Trough concentration of cefazolin measured in plasma samples

Time frame: 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)

Total plasma concentrations of cefazolin in plasma samples

Time frame: 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)

Free drug concentrations of cefazolin in plasma samples

Trough concentration of cefazolin in sweat samples

Trough concentration of cefazolin measured in sweat samples