<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04503252</url>
  </required_header>
  <id_info>
    <org_study_id>2019-02229; me20Osthoff2</org_study_id>
    <nct_id>NCT04503252</nct_id>
  </id_info>
  <brief_title>Probability of Target Attainment With Standard Intermittent Bolus Administration of Cefazolin in Patients With Complicated Infections Caused by Staphylococcus Aureus</brief_title>
  <acronym>TARGET II</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>propatient foundation Basel</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Given the paucity of pharmacological data on cefazolin treatment of Methicillin-susceptible&#xD;
      S. aureus (MSSA) complicated S. aureus infection (CSAI), the primary purpose of this study is&#xD;
      to investigate the probability of pharmacological target attainment (in the blood and&#xD;
      infected tissue) with standard intermittent bolus administration of cefazolin in patients&#xD;
      with CSAI caused by MSSA by determining plasma concentrations of cefazolin and exact Minimum&#xD;
      inhibitory concentration (MICs) of the causative MSSA strains in patients with various&#xD;
      disease severities (e.g. critically ill vs. noncritically ill patients).&#xD;
&#xD;
        -  Sub-study quantitative measurement of Torque Teno virus (TTV): The primary purpose of&#xD;
           this sub-study is to describe the viral kinetics of TTV in CSAI patients and to explore&#xD;
           the association of TTV viremia with clinical outcomes and molecular markers of&#xD;
           activation of the immune system.&#xD;
&#xD;
        -  Sub-study investigating antibiotic concentrations in sweat as a non-invasive therapeutic&#xD;
           drug monitoring&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2020</start_date>
  <completion_date type="Actual">March 28, 2022</completion_date>
  <primary_completion_date type="Actual">March 28, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Trough concentration of cefazolin in plasma samples</measure>
    <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)</time_frame>
    <description>Trough concentration of cefazolin measured in plasma samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total plasma concentrations of cefazolin in plasma samples</measure>
    <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)</time_frame>
    <description>Total plasma concentrations of cefazolin in plasma samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Free drug concentrations of cefazolin in plasma samples</measure>
    <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)</time_frame>
    <description>Free drug concentrations of cefazolin in plasma samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough concentration of cefazolin in sweat samples</measure>
    <time_frame>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)</time_frame>
    <description>Trough concentration of cefazolin measured in sweat samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total sweat concentrations of cefazolin</measure>
    <time_frame>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)</time_frame>
    <description>Total sweat concentrations of cefazolin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Free drug concentrations of cefazolin in sweat samples</measure>
    <time_frame>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)</time_frame>
    <description>Free drug concentrations of cefazolin in sweat samples</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Target attainment (100%fT&gt;MIC)</measure>
    <time_frame>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)</time_frame>
    <description>Antibiotic susceptibility of the isolated pathogens determined by the use of an Minimum inhibitory concentration (MIC) test strip. Target attainment (100%fT&gt;MIC) will be calculated for each patient and for each day the patient was sampled. Target attainment is defined as a measured free trough plasma concentration of cefazolin above the measured exact MICs of the causative pathogens at all points of time sampled.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacological target attainment (100%fT&gt;MIC) in infected tissue</measure>
    <time_frame>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)</time_frame>
    <description>For the analysis of pharmacological target attainment (100%fT&gt;MIC) in infected tissue (only patients with a suggestive focus or metastatic complication of BSI will be included for this analysis) free trough concentration of cefazolin will be measured in plasma samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attainment of an accepted threshold for toxicity (100%fT&gt;10xMIC) in blood</measure>
    <time_frame>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)</time_frame>
    <description>For the analysis of attainment of an accepted threshold for toxicity (100%fT&gt;10xMIC) in blood, trough free concentration of cefazolin will be measured in plasma samples. Attainment of the threshold for toxicity is defined as measured free trough plasma concentration of cefazolin above at least 10x the measured exact MIC or above the clinical breakpoint MIC of the causative pathogen as published by the European Committee on Antimicrobial Susceptibility Testing at one time point or more. Cefazolin concentrations in sweat will be compared between patients with attained toxicity and non-attained thresholds in plasma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of cefazolin tolerance of the isolated pathogen</measure>
    <time_frame>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)</time_frame>
    <description>The level of cefazolin tolerance of the isolated pathogen will be determined by the tolerance disc test as well as through time-kill curves. The level of tolerance determines the required antibiotic concentration to achieve bactericidal killing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTV substudy: quantification of DNA</measure>
    <time_frame>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)</time_frame>
    <description>For the TTV substudy DNA will be extracted from ethylenediaminetetraacetic acid (EDTA) blood and quantified</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTV substudy: quantification of cytokines</measure>
    <time_frame>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)</time_frame>
    <description>Cytokines as a markers of the activation status of the immune system will be quantified by using commercially available ELISA kits.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Staphylococcus Aureus Infection</condition>
  <arm_group>
    <arm_group_label>Study population: patients with CSAI caused by MSSA</arm_group_label>
    <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 &lt;60ml/min, at least 10 patients with BSI).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-study: Torque Teno virus (TTV) viremia</arm_group_label>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-study: cefazolin concentrations in sweat</arm_group_label>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood samples for the measurement of the concentration of cefazolin</intervention_name>
    <description>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).</description>
    <arm_group_label>Study population: patients with CSAI caused by MSSA</arm_group_label>
    <arm_group_label>Sub-study: Torque Teno virus (TTV) viremia</arm_group_label>
    <arm_group_label>Sub-study: cefazolin concentrations in sweat</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>S. aureus culture isolate</intervention_name>
    <description>The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.</description>
    <arm_group_label>Study population: patients with CSAI caused by MSSA</arm_group_label>
    <arm_group_label>Sub-study: Torque Teno virus (TTV) viremia</arm_group_label>
    <arm_group_label>Sub-study: cefazolin concentrations in sweat</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>structured telephone interview</intervention_name>
    <description>Structured telephone interview for Patient follow- up after 30 days</description>
    <arm_group_label>Study population: patients with CSAI caused by MSSA</arm_group_label>
    <arm_group_label>Sub-study: Torque Teno virus (TTV) viremia</arm_group_label>
    <arm_group_label>Sub-study: cefazolin concentrations in sweat</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sub-study quantitative measurement of Torque Teno virus</intervention_name>
    <description>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.</description>
    <arm_group_label>Sub-study: Torque Teno virus (TTV) viremia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sub-study investigating cefazolin concentrations in sweat</intervention_name>
    <description>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.</description>
    <arm_group_label>Sub-study: cefazolin concentrations in sweat</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      All bacterial isolates from the patients will be stored in the biobank of the microbiology&#xD;
      department of the University Hospital Basel.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Inpatients with CSAI fulfilling the inclusion criteria and admitted at the University&#xD;
        Hospital Basel.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CSAI caused by MSSA. CSAI is defined as MSSA BSI with a positive follow-up blood&#xD;
             culture result for MSSA or the presence of a site of infection remote from the primary&#xD;
             focus caused by hematogenous seeding (e.g. endocarditis, vertebral osteomyelitis) or&#xD;
             extension of the infection beyond the primary focus (e.g. septic thrombophlebitis or&#xD;
             abscess); or deep-seated infections caused by MSSA (e.g. osteoarticular infections,&#xD;
             deepseated abscesses).&#xD;
&#xD;
          -  Current or intended treatment with cefazolin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous enrolment into the current study within 30 days&#xD;
&#xD;
          -  Hemodialysis (patients on hemofiltration are eligible)&#xD;
&#xD;
          -  Patients who are very likely to stop treatment with cefazolin in the next 48 hours as&#xD;
             per treating physician (because of treatment failure, switch to oral medication,&#xD;
             palliative care, allergy etc.) or who are very likely to be discharged in the next 48&#xD;
             hours as per treating physician.&#xD;
&#xD;
          -  Outpatients&#xD;
&#xD;
          -  Women who are pregnant (special pharmacokinetic)&#xD;
&#xD;
          -  Polymicrobial infection except concomitant isolation of a likely contaminant (e.g.&#xD;
             Staphylococcus epidermidis or Propionibacterium acnes) or an anaerobic pathogen. If an&#xD;
             additional pathogen is identified after inclusion of the patient into the study, the&#xD;
             patient will remain in the study.&#xD;
&#xD;
          -  Not-complicated S. aureus infections: non-bacteremic skin- and soft tissue or small&#xD;
             Joint infections without deep-seated abscesses (as these patients will be quickly&#xD;
             switched to oral antibiotics)&#xD;
&#xD;
          -  CSAI caused by methicillin-resistant S. aureus (MRSA)&#xD;
&#xD;
        Additional exclusion criteria for the sub-study investigating cefazolin concentrations in&#xD;
        sweat:&#xD;
&#xD;
          -  Allergic to pilocarpine&#xD;
&#xD;
          -  Continuous oxygen therapy without the possibility to interrupt oxygen administration&#xD;
             for 10min&#xD;
&#xD;
          -  Pacemaker&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Osthoff, PD Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Basel, Division of Internal Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Basel, Division of Internal Medicine</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bloodstream infection (BSI)</keyword>
  <keyword>Minimum inhibitory concentration (MIC)</keyword>
  <keyword>Methicillin-susceptible S. aureus (MSSA)</keyword>
  <keyword>Staphylococcus aureus (S. aureus)</keyword>
  <keyword>β-lactam antibiotics</keyword>
  <keyword>flucloxacillin</keyword>
  <keyword>cefazolin</keyword>
  <keyword>pharmacological target attainment</keyword>
  <keyword>Torque Teno virus (TTV)</keyword>
  <keyword>Therapeutic drug monitoring (TDM)</keyword>
  <keyword>antibiotic sweat concentrations</keyword>
  <keyword>Complicated S. aureus infection (CSAI)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Staphylococcal Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cefazolin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04503252
org study id: 2019-02229; me20Osthoff2
nct id: NCT04503252
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
observational model: Cohort
time perspective: Prospective
measure: Trough concentration of cefazolin 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)
description: Trough concentration of cefazolin measured in plasma samples
measure: 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)
description: Total plasma concentrations of cefazolin in plasma samples
measure: Free drug 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)
description: Free drug concentrations of cefazolin in plasma samples
measure: Trough concentration of cefazolin in sweat samples
time frame: 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)
description: Trough concentration of cefazolin measured in sweat samples
measure: Total sweat concentrations of cefazolin
time frame: 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)
description: Total sweat concentrations of cefazolin
measure: Free drug concentrations of cefazolin in sweat samples
time frame: 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)
description: Free drug concentrations of cefazolin in sweat samples
measure: Target attainment (100%fT>MIC)
time frame: 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)
description: Antibiotic susceptibility of the isolated pathogens determined by the use of an Minimum inhibitory concentration (MIC) test strip. Target attainment (100%fT>MIC) will be calculated for each patient and for each day the patient was sampled. Target attainment is defined as a measured free trough plasma concentration of cefazolin above the measured exact MICs of the causative pathogens at all points of time sampled.
measure: Pharmacological target attainment (100%fT>MIC) in infected tissue
time frame: 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)
description: For the analysis of pharmacological target attainment (100%fT>MIC) in infected tissue (only patients with a suggestive focus or metastatic complication of BSI will be included for this analysis) free trough concentration of cefazolin will be measured in plasma samples.
measure: Attainment of an accepted threshold for toxicity (100%fT>10xMIC) in blood
time frame: 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)
description: For the analysis of attainment of an accepted threshold for toxicity (100%fT>10xMIC) in blood, trough free concentration of cefazolin will be measured in plasma samples. Attainment of the threshold for toxicity is defined as measured free trough plasma concentration of cefazolin above at least 10x the measured exact MIC or above the clinical breakpoint MIC of the causative pathogen as published by the European Committee on Antimicrobial Susceptibility Testing at one time point or more. Cefazolin concentrations in sweat will be compared between patients with attained toxicity and non-attained thresholds in plasma.
measure: Level of cefazolin tolerance of the isolated pathogen
time frame: 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)
description: The level of cefazolin tolerance of the isolated pathogen will be determined by the tolerance disc test as well as through time-kill curves. The level of tolerance determines the required antibiotic concentration to achieve bactericidal killing.
measure: TTV substudy: quantification of DNA
time frame: 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)
description: For the TTV substudy DNA will be extracted from ethylenediaminetetraacetic acid (EDTA) blood and quantified
measure: TTV substudy: quantification of cytokines
time frame: 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)
description: Cytokines as a markers of the activation status of the immune system will be quantified by using commercially available ELISA kits.
arm group label: 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).
arm group label: 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.
arm group label: 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.
intervention type: Other
intervention name: Blood samples for the measurement of the concentration of cefazolin
description: 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).
arm group label: Study population: patients with CSAI caused by MSSA
arm group label: Sub-study: Torque Teno virus (TTV) viremia
arm group label: Sub-study: cefazolin concentrations in sweat
intervention type: Other
intervention name: S. aureus culture isolate
description: The S. aureus culture isolate will be subjected to exact cefazolin MIC determination and to measurement of the level of cefazolin tolerance.
arm group label: Study population: patients with CSAI caused by MSSA
arm group label: Sub-study: Torque Teno virus (TTV) viremia
arm group label: Sub-study: cefazolin concentrations in sweat
intervention type: Other
intervention name: structured telephone interview
description: Structured telephone interview for Patient follow- up after 30 days
arm group label: Study population: patients with CSAI caused by MSSA
arm group label: Sub-study: Torque Teno virus (TTV) viremia
arm group label: Sub-study: cefazolin concentrations in sweat
intervention type: Other
intervention name: Sub-study quantitative measurement of Torque Teno virus
description: 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.
arm group label: Sub-study: Torque Teno virus (TTV) viremia
intervention type: Other
intervention name: Sub-study investigating cefazolin concentrations in sweat
description: 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.
arm group label: Sub-study: cefazolin concentrations in sweat
All bacterial isolates from the patients will be stored in the biobank of the microbiology
      department of the University Hospital Basel.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Osthoff, PD Dr. med.
role: Principal Investigator
affiliation: University Hospital Basel, Division of Internal Medicine
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Staphylococcal Infections
mesh term: Cefazolin