title: Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.
abstract: BACKGROUND
  The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases.
  
  
  CONCLUSIONS
  Our results propose individual therapeutic drug monitoring taking into account: For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in renal disease (MDRD). • For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity. AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia.
  
  
  METHODS
  A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40-100 mg l(-1) was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target.
  
  
  RESULTS
  Steady-state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min(-1) , 6 g for MDRD between 40 and 80 ml min(-1) , 8 g for MDRD from 90 to 110 ml min(-1) , 10 g for MDRD from 120 to 190 ml min(-1) and 12 g day(-1) for patients with MDRD higher than 200 ml min(-1) .
  
  
  CONCLUSIONS
  Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.
authors: Pôle d'Anesthésie Réanimation, CHU Rangueil, TSA 50032, Toulouse, France.
authors: Bernard
authors: B
authors: Georges
authors: Jean-Marie
authors: JM
authors: Conil
authors: Stéphanie
authors: S
authors: Ruiz
authors: Thierry
authors: T
authors: Seguin
authors: Pierre
authors: P
authors: Cougot
authors: Olivier
authors: O
authors: Fourcade
authors: Georges
authors: G
authors: Houin
authors: Sylvie
authors: S
authors: Saivin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003198:Computer Simulation; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D012121:Respiration, Artificial
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime