title: Pharmacodynamics of meropenem in critically ill patients with ventilator-associated pneumonia.
abstract: BACKGROUND
  Pharmacokinetic changes have been found in critically ill patients, including ventilator-associated pneumonia (VAP) when compared with healthy volunteers leading to fluctuation of plasma concentrations.
  
  
  OBJECTIVE
  To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for meropenem between administration by a bolus injection and a 3-hour infusion.
  
  
  METHODS
  The study was a randomized three-way crossover in nine patients with VAP. Each patient received meropenem in three regimens consecutively: (i) a bolus injection of 1 g every eight hours (q8h) for 24 hours; (ii) a 3-hour infusion of 1 g q8h for 24 hours; and (iii) a 3-hour infusion of 2 g q8h for 24 hours. The pharmacodynamic analysis of meropenem was performed to determine the PTA by using the Monte Carlo simulation and the study used susceptibility patterns obtained from EUCAST and MYSTIC for assessment of CFR.
  
  
  RESULTS
  For an MIC of 4 microg/ml, the PTAs achieving 40% T > MIC following a bolus injection of 1 g q8h, a 3-hour infusion of 1 g q8h, and a 3-hour infusion of 2 g q8h were 87.71%, 98.80%, and 99.90%, respectively. Only the 3-hour infusion regimens were predicted to achieve a CFR > or = 90% against E. coli, Klebsiella spp., P. aeruginosa, and Acinetobacter spp.
  
  
  CONCLUSIONS
  A 3-hour infusion of 2 g of meropenem regimen was predicted to have the highest PTA rates. Only the prolonged infusion regimens achieved a high CFR against E. coli, Klebsiella spp., P. aeruginosa, and Acinetobacter 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.affiliation: Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Narongdet
authors.initials: N
authors.lastname: Kositpantawong
authors.affiliation: Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Monchana
authors.initials: M
authors.lastname: Jullangkoon
authors.affiliation: Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Nanchanit
authors.initials: N
authors.lastname: Aeinlang
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Wibul
authors.initials: W
authors.lastname: Wongpoowarak
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007267:Injections; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D009010:Monte Carlo Method; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology*; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem