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

University Hospital Basel

Status: Completed

Conditions: Staphylococcus Aureus Infection

Treatments: Other: Blood samples for the measurement of the concentration of cefazolin; Other: Sub-study quantitative measurement of Torque Teno virus; Other: S. aureus culture isolate; Other: Sub-study investigating cefazolin concentrations in sweat; Other: structured telephone interview

Study type: Observational

Funder types: Other

Identifiers

NCT04503252

2019-02229 me20Osthoff2;

Details and patient eligibility

About

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

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

50 participants in 3 patient groups

Study population: patients with CSAI caused by MSSA

Description:

Inpatients with CSAI caused by MSSA treated or intended to receive cefazolin within the next 24-48 hours (at least 10 (maximum of 20) critically-ill patients, at least 10 (maximum of 20) patients with an estimated glomerular filtration rate of \<60ml/min, at least 10 patients with BSI).

Treatment:

Other: structured telephone interview

Other: Blood samples for the measurement of the concentration of cefazolin

Other: S. aureus culture isolate

Sub-study: Torque Teno virus (TTV) viremia

Description:

TTV viral load may indicate the immunological status of the host. The TTV sub-study is to to describe the viral kinetics of TTV in CSAI patients.

Treatment:

Other: structured telephone interview

Other: Blood samples for the measurement of the concentration of cefazolin

Other: S. aureus culture isolate

Other: Sub-study quantitative measurement of Torque Teno virus

Sub-study: cefazolin concentrations in sweat

Description:

Out of the study population (patients with CSAI) a total of 15 CSAI patients will be included for the substudy investigating cefazolin concentrations in sweat as a non-invasive therapeutic drug monitoring.

Treatment:

Other: structured telephone interview

Other: Blood samples for the measurement of the concentration of cefazolin

Other: Sub-study investigating cefazolin concentrations in sweat

Other: S. aureus culture isolate