title: Pharmacokinetics of short versus extended infusion meropenem dosing in critically ill patients: a pilot study.
abstract: OBJECTIVE
  To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes.
  
  
  METHODS
  A randomised crossover study in 10 critically ill patients.
  
  
  METHODS
  We administered meropenem as a 1000mg, 30-minute infusion or as a 500mg, 3-hour infusion. We determined serial plasma concentrations for each dosing episode and performed comparisons of %TMIC at different MICs.
  
  
  METHODS
  The percentage of time that meropenem was above its MIC.
  
  
  RESULTS
  For low MICs (≤2 mg/L), both regimens attained a %TMIC >40% in all patients. For an MIC of 4mg/L, this target was attained in all but one patient, but with an MIC of 8mg/L, three patients in each group had a %TMIC <40%. There was no difference in target attainment between the two regimens for MICs up to 8mg/L. There was marked variability in the pharmacokinetic and hence the pharmacokinetic-pharmacodynamic parameters between individuals. Several patients had elevated creatinine clearances and, with both regimens, their target attainment was poor.
  
  
  CONCLUSIONS
  Meropenem at 1000mg over 30 minutes achieved a similar %TMIC to meropenem at 500mg given over 3 hours. Meropenem pharmacokinetics were highly variable from individual to individual.
authors.affiliation: Department of Infectious Diseases, Austin Health, Melbourne, VIC, Australia. rinaldo.bellomo@austin.org.au.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Langan
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Jovan
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Department of Infectious Diseases, Austin Health, Melbourne, VIC, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Howden
authors.affiliation: Department of Infectious Diseases, Austin Health, Melbourne, VIC, Australia.
authors.forename: Paul D R
authors.initials: PD
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem