Surgery and intensive care procedures affect the target site distribution of piperacillin

Objective: Therapeutic failure of antibiotic therapy has been ascribed to p harmacokinetic 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 inte rstitial space fluid, the relevant target site for most bacterial infection s, was compared between patients after aortic valve replacement and healthy volunteers. Design: Comparative study in two study populations. Setting: The intensive care unit and research ward of a university hospital . Patients: The study population included six otherwise healthy patients sche duled to undergo aortic valve replacement and a control group of six health y male volunteers. Interventions: After the administration of a single iv infusion of 4.0 g pi peracillin, free piperacillin concentrations were measured in the interstit ium of skeletal muscle and subcutaneous tissue by in vivo microdialysis and in venous serum. Piperacillin concentrations were assayed with reversed ph ase high-performance liquid chromatography. Measurements and Main 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 interstitiu m/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 < .0 5 between groups). The terminal elimination half-life was markedly prolonge d 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 MIG(50) <4 mu g/m L. For strains with MIC50 >20 mu l/mL, however, inadequate target site conc entrations were attained in the patient population. Conclusions: During the postoperative and intensive care periods, target si te concentrations of piperacillin are markedly altered and decreased. This may also be true for other antibiotic agents and may have clinical implicat ions in that current dosing guidelines may result in inadequate target site concentrations for high-MIG strains. Conceivably, this could lead to thera peutic failure in some patients.