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

NCT ID: NCT04503252

Last Updated: 2022-03-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-14
• Study Completion Date: 2022-03-28

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

Conditions

Staphylococcus Aureus Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Study population: patients with CSAI caused by MSSA

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).

Blood samples for the measurement of the concentration of cefazolin

Intervention Type: OTHER

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).

S. aureus culture isolate

Intervention Type: OTHER

The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.

structured telephone interview

Intervention Type: OTHER

Structured telephone interview for Patient follow- up after 30 days

Sub-study: Torque Teno virus (TTV) viremia

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.

Blood samples for the measurement of the concentration of cefazolin

Intervention Type: OTHER

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).

S. aureus culture isolate

Intervention Type: OTHER

The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.

structured telephone interview

Intervention Type: OTHER

Structured telephone interview for Patient follow- up after 30 days

Sub-study quantitative measurement of Torque Teno virus

Intervention Type: OTHER

An additional EDTA sample will be drawn for quantitative polymerase chain reaction (PCR) of TTV DNA and analyses of cytokines and other parameters of the activation state of the immune system.

Sub-study: cefazolin concentrations in sweat

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.

Blood samples for the measurement of the concentration of cefazolin

Intervention Type: OTHER

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).

S. aureus culture isolate

Intervention Type: OTHER

The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.

structured telephone interview

Intervention Type: OTHER

Structured telephone interview for Patient follow- up after 30 days

Sub-study investigating cefazolin concentrations in sweat

Intervention Type: OTHER

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.

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).

Intervention Type: OTHER

S. aureus culture isolate

The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.

Intervention Type: OTHER

structured telephone interview

Structured telephone interview for Patient follow- up after 30 days

Intervention Type: OTHER

Sub-study quantitative measurement of Torque Teno virus

An additional EDTA sample will be drawn for quantitative polymerase chain reaction (PCR) of TTV DNA and analyses of cytokines and other parameters of the activation state of the immune system.

Intervention Type: OTHER

Sub-study investigating cefazolin concentrations in sweat

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.

Intervention Type: OTHER

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

propatient foundation Basel

UNKNOWN

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Osthoff, PD Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Division of Internal Medicine

Locations

University Hospital Basel, Division of Internal Medicine

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

2019-02229; me20Osthoff2

Identifier Type: -

Identifier Source: org_study_id