title: Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.
abstract: OBJECTIVE
  The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia.
  
  
  METHODS
  Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method.
  
  
  RESULTS
  Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma.
  
  
  CONCLUSIONS
  The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.
authors.affiliation: Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium f.frippiat@chu.ulg.ac.be.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frippiat
authors.affiliation: School of Pharmacy, University College, London, UK.
authors.forename: Flora Tshinanu
authors.initials: FT
authors.lastname: Musuamba
authors.affiliation: Department of Biostatistics, University Hospital of Liège, Liège, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Seidel
authors.affiliation: Department of Biostatistics, University Hospital of Liège, Liège, Belgium.
authors.forename: Adelin
authors.initials: A
authors.lastname: Albert
authors.affiliation: Department of Toxicology, University Hospital of Liège, Liège, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Denooz
authors.affiliation: Department of Toxicology, University Hospital of Liège, Liège, Belgium.
authors.forename: Corinne
authors.initials: C
authors.lastname: Charlier
authors.affiliation: Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
authors.affiliation: Department of Microbiology, University Hospital of Liège, Liège, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Descy
authors.affiliation: Intensive Care Unit, University Hospital of Liège, Liège, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lambermont
authors.affiliation: Intensive Care Unit, University Hospital of Liège, Liège, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Layios
authors.affiliation: Intensive Care Unit, University Hospital of Liège, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Damas
authors.affiliation: Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000737:chemistry; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: Monte Carlo simulations; critically ill patients; epithelial lining fluid concentrations