title: Surgery and intensive care procedures affect the target site distribution of piperacillin.
abstract: OBJECTIVE
  Therapeutic failure of antibiotic therapy has been ascribed to pharmacokinetic alterations in compromised patient populations. The present study, therefore, aimed at examining the influences of cardiac surgery and intensive care procedures on the postoperative target site distribution of piperacillin. For this purpose, the penetration of piperacillin to the interstitial space fluid, the relevant target site for most bacterial infections, was compared between patients after aortic valve replacement and healthy volunteers.
  
  
  METHODS
  Comparative study in two study populations.
  
  
  METHODS
  The intensive care unit and research ward of a university hospital.
  
  
  METHODS
  The study population included six otherwise healthy patients scheduled to undergo aortic valve replacement and a control group of six healthy male volunteers.
  
  
  METHODS
  After the administration of a single i.v. infusion of 4.0 g piperacillin, free piperacillin concentrations were measured in the interstitium of skeletal muscle and subcutaneous tissue by in vivo microdialysis and in venous serum. Piperacillin concentrations were assayed with reversed phase high-performance liquid chromatography.
  
  
  RESULTS
  Interstitial piperacillin concentrations in muscle and subcutaneous adipose tissue were significantly lower in patients compared with volunteers with the area under the curve for the interstitium/area under the curve for serum concentration ratios ranging from 0.25 to 0.27 and from 0.43 to 1.22 in patients and volunteers, respectively (p < .05 between groups). The terminal elimination half-life was markedly prolonged in patients, leading to a concomitant increase in t > minimal inhibitory concentration (MIC) values, the relevant surrogate for therapeutic success of therapy with beta-lactam antibiotics, for strains with MIC50 <4 microg/mL. For strains with MIC50 >20 microl/mL, however, inadequate target site concentrations were attained in the patient population.
  
  
  CONCLUSIONS
  During the postoperative and intensive care periods, target site concentrations of piperacillin are markedly altered and decreased. This may also be true for other antibiotic agents and may have clinical implications in that current dosing guidelines may result in inadequate target site concentrations for high-MIC strains. Conceivably, this could lead to therapeutic failure in some patients.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna Medical School, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Brunner
authors.forename: T
authors.initials: T
authors.lastname: Pernerstorfer
authors.forename: B X
authors.initials: BX
authors.lastname: Mayer
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: M
authors.initials: M
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003422:Critical Care / Q000379:methods*; D005110:Extracellular Space / Q000378:metabolism; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000493:pharmacokinetics*; D010878:Piperacillin / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D010406:Penicillins; D010878:Piperacillin