Cefazolin, 1 gram fits all?

Rationale: The basic principle of surgical antibiotic prophylaxis is the
attainment of adequate levels of antibiotic in the tissue before and throughout
the period of potential bacterial contamination. The duration and adequacy of
antibiotic levels in the tissues is mainly determined by the pharmacokinetic
characteristics of the antibiotic, e.g. volume of distribution, clearance and
the rate and extent by which the drug penetrates in the target tissue.
The Dutch guideline for perioperative antibiotic prophylaxis recommends a
standard dose of 1 gram of cefazolin for most surgical procedures. Although
this dose may be sufficient for most patients, it is however not clear whether
adequate antibiotic concentrations are reached in obese patients. In fact, some
studies have demonstrated that obesity is a risk factor for post-operative
wound infection. Furthermore, there is limited information with respect to the
effect of overweight on pharmacokinetics and clinical efficacy of most
antimicrobials.

Objective: 1) to assess whether adequate serum and interstitial fluid levels of
cefazolin are reached during surgery in obese and non-obese patients, 2) to
develop a population pharmacokinetic model for cefazolin which allows the
characterization of the relationship between body size and the pharmacokinetic
parameters and 3) to implement the results in daily practice.

Study design: Observational cohort study (Sept 2007 - Sept 2008).

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The risks associated with participation are
minimal since perioperative antibiotic prophylaxis is administered in
accordance with the Dutch Guidelines. During surgery a total extra volume of
approximately 30-40 ml blood will be drawn. In 15 patients a subcutaneous
microdialysis catheter will be placed for determination of interstitial fluid
concentrations. The burden of this catheter is minimal.