probability of target attainment with standard intermittent bolus administration of cefazolin in patients with complicated infections caused by staphylococcus aureus

Conditions: Staphylococcus Aureus Infection

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

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)