Pharmacodynamics of piperacillin in severely ill patients evaluated by using a PK/PD model.
Penetration of antiinfective drugs into soft tissues is essential for antimicrobial killing at the target site, but is substantially lower in severely ill patients compared with healthy subjects. The present study was conducted to assess the antimicrobial effect of piperacillin in severely ill patients. Strains of Staphylococcus aureus and Pseudomonas aeruginosa were exposed in vitro to concentrations of piperacillin, simulating the pharmacokinetic profiles measured in soft tissue of patients and healthy subjects. The simulation for patients resulted in effective killing, whereas bacterial regrowth was detected for healthy subjects. Our in vitro simulation showed that bacterial killing may be effective in severely ill patients despite relatively low concentrations of piperacillin at the target site. This finding is due to impaired renal function and subsequently prolonged tissue and plasma half-lives of piperacillin in intensive care patients.
Sauermann
Robert
R
Department of Clinical Pharmacology, University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, A-1090, Vienna, Austria.
Zeitlinger
Markus
M
Erovic
Boban M
BM
Marsik
Claudia
C
Georgopoulos
Apostolos
A
Müller
Markus
M
Brunner
Martin
M
Joukhadar
Christian
C
D015169:Colony Count, Microbial; D016638:Critical Illness; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010878:Piperacillin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
D010878:Piperacillin