Model for PK/PD of Antimicrobials in Blood Stream Infection: Feasibility
Model for PK/PD of Antimicrobials in Blood Stream Infection: Feasibility
The current study is a pilot study to assess the feasibility of a superordinate project. The
 final objective of this superordinate project is to describe and model the pharmacokinetic
 behaviour of a small number of standard antimicrobials used in the treatment of frequent
 blood stream infections, and to link this via pharmacodynamic models to (inhibition of)
 bacterial or fungal growth as well as to clinical outcomes in patients.
Patients with a high probability of a blood stream infection and an indication for
 antimicrobial treatment will be included. The study comprises the identification of patients
 as potential study participants, obtaining informed consent, documentation of available
 potential covariates from patient file, withdrawal of pre-study blood samples (PK, PD,
 microbiology) including documentation of exact time of sampling and processing of the
 samples, first drug administration including exact documentation (as part of patient care;
 not as a study intervention), withdrawal of subsequent blood samples (PK, PD, microbiology)
 during the next 3 days including documentation of exact time of sampling and processing of
 the samples, storage of processed samples for further analysis, and, if possible,
 documentation of patient outcome after 7 days. The following steps are carried out after
 completion of the clinical part of the study in the individual patient or, when possible, in
 all patients together or in a subset: Bioanalytics, DNA Counts, assessing primary and
 secondary study endpoints, pharmacometric analyses including PK parameter estimation, PD
 parameter estimation and assessment of covariate effects with regard to DNA count, CRP, IL-6
 and procalcitonin.
Inclusion Criteria:

 -  High probability of a blood stream infection; this is based on

 -  the presence of SIRS [Bone et al. 1992] defined by more than one of the following
 clinical manifestations:

 1. a body temperature greater than 38°C or less than 36°C

 2. a heart rate greater than 90 beats per minute

 3. tachypnea, manifested by a respiratory rate greater than 20 breaths per
 minute, or hyperventilation, as indicated by a PaCO2 of less than 32 mm Hg

 4. an alteration in the white blood cell count, such as a count greater than
 12,000/µl, a count less than 4,000/µl, or the presence of more than 10
 percent immature neutrophils ("bands").

 and

 -  the assessment of the treating physician according to the patient's situation
 that the SIRS is caused by an infection (e.g., patients after treatment with
 cytotoxic drugs)

 -  indication for antimicrobial treatment

 -  Intended use of one of the following antimicrobial agents:

 piperacillin/tazobactam; vancomycin; meropenem; ampicillin/sulbactam; flucloxacillin;
 ceftriaxone; caspofungin (according to the decision of the project coordinator, use of
 other antimicrobial agents may also be included if anticipated to be used frequently)

 -  Age: 18 years or older (no upper limit)

 -  Willing and capable to provide written consent prior to enrolment after ample
 information has been provided

 Exclusion Criteria:

 -  expected chances to successfully carry out venipunctures to obtain the blood samples
 required for the study are inadequately low according to the assessment of the
 physician

 -  Anemia CTCAE grade >2 (i.e., Hb <8.0 g/dL / 4.9 mmol/L)

 -  the clinical status of the patients suggests that the anticipated treatment of the
 patient or other conditions would make participation on the study inappropriate (e.g.,
 terminally ill patients); the respective assessment is done by the treating physician