title: Pharmacodynamics of imipenem in critically ill patients with ventilator-associated pneumonia.
abstract: BACKGROUND
  Drug dispositions are altered in critically ill patients, including ventilator-associated pneumonia (VAP) when compared with healthy subjects leading to fluctuations of plasma concentrations.
  
  
  OBJECTIVE
  To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for imipenem between administration by 0.5-hour and 2-hour infusions.
  
  
  METHODS
  The present study was a randomized three-way crossover in nine patients with VAP Each patient received imipenem in three regimens consecutively: (i) a 0.5-hour infusion of 0.5 g every six hours for 24 hours; (ii) a 2-hour infusion of 0.5 g every six hours for 24 hours; and (iii) a 2-hour infusion of 1 g every six hours for 24 hours. Monte Carlo simulation was performed to determine the PTA at various regimens and the study used susceptibility patterns obtained from EUCAST and MYSTIC for assessment of CFR.
  
  
  RESULTS
  For an MIC of 2 microg/ml, the PTAs achieving 40% T > MIC following a 0.5-hour infusion of 0.5 g, a 2-hour infusion of 0.5 g, and a 2-hour infusion of 1 g were 90.93%, 98.97%, and 100%, respectively. Only a 2-hour infusion of 1 g achieved 98.75% of the PTA of 40% T > MGC for an MIC of 4 microg/ml. All regimens were predicted to achieve CFR > 99% against E. coli and Klebsiella spp.
  
  
  CONCLUSIONS
  A 2-hour infusion of 1 g regimen was predicted to have the highest PTA rates. All regimens achieved a high CFR against E. coli and Klebsiella spp.
authors.affiliation: Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. jasutep@medicine.psu.ac.th
authors.forename: Sutep
authors.initials: S
authors.lastname: Jaruratanasirikul
authors.forename: Nanchanit
authors.initials: N
authors.lastname: Aeinlang
authors.forename: Monchana
authors.initials: M
authors.lastname: Jullangkoon
authors.forename: Wibul
authors.initials: W
authors.lastname: Wongpoowarak
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D012121:Respiration, Artificial / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem