title: Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration.
abstract: OBJECTIVE
  The pharmacokinetics of ceftazidime, the antibiotic of choice for treating acute P. aeruginosa infections, may be modified in burns patients. The aim of this study was to identify the factors causing variations in the serum antibiotic concentrations in bums patients.
  
  
  METHODS
  30 patients with serious burns were randomly divided into two groups. Group 1 received a dose of ceftazidime of 2 x 3 g/24 hours. The second group received the same dose but divided into 6 administrations. Blood samples were taken at 24 (M1) and 48 hours (M2) after the start of treatment and the peak and trough serum concentrations of ceftazidime measured by HPLC. Depending on the results, frequency and/or dose was modified to obtain trough concentrations (Cmin) equal to 16 mg/l, i.e. 4 times the MIC. Either the same dose was maintained, but mostly divided up, or it was increased to 1 g x 8 administrations or it was decreased to 1 g x 4 or 1 g x 3. The serum concentrations of ceftazidime obtained were analyzed taking into account the characteristics of the burns patients (multivariate correlation).
  
  
  RESULTS
  From the first sample (M1) Cmin was lower than the target concentration in 50% of the patients in Group 1 and 20% in Group 2. The modification of the dosing regimen put into place after the first analysis, led to the patients being further divided into four groups before the second blood sampling. Finally, 5 patients ended up in Group 1. In all patients and for all administration times, a negative correlation was found between Cmin and the creatinine clearance, calculated by using Cockcroft's formula.
  
  
  CONCLUSIONS
  This study highlights the peculiarities of ceftazidime pharmacokinetics seen in burns patients with high interindividual variability. Based on Cmin monitoring and a predefined therapeutic range, dose adjustment was often required. Ceftazidime clearance is correlated with creatinine clearance (Cockcroft's formula), suggesting that this parameter could be used for a priori or a posteriori dose individualization. To respect the summary of the product characteristics (SPC) and reduce the variability in trough concentrations, the dose should be fractionated (1 g x 6) over a 24-hour period or even given as a continuous infusion. Trough concentrations must be evaluated to adapt the dosage regimen to attain target concentrations of 4 x the MIC.
authors.affiliation: Service d'Anesthésie-Réanimation, Toulouse, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Conil
authors.forename: B
authors.initials: B
authors.lastname: Georges
authors.forename: O
authors.initials: O
authors.lastname: Fourcade
authors.forename: T
authors.initials: T
authors.lastname: Seguin
authors.forename: G
authors.initials: G
authors.lastname: Houin
authors.forename: S
authors.initials: S
authors.lastname: Saivin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D002442:Ceftazidime / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006801:Humans; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime