title: Microdialysis study of cefotaxime cerebral distribution in patients with acute brain injury.
abstract: Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Microdialysis probes were inserted into healthy brain tissue of five critical care patients. Plasma and unbound brain concentrations were determined at steady state by high-performance liquid chromatography. In vivo recoveries were determined individually using retrodialysis by drug. Noncompartmental and compartmental pharmacokinetic analyses were performed. Unbound cefotaxime brain concentrations were much lower than corresponding plasma concentrations, with a mean cefotaxime unbound brain-to-plasma area under the curve ratio equal to 26.1 ± 12.1%. This result was in accordance with the brain input-to-brain output clearances ratio (CL(in,brain)/CL(out,brain)). Unbound brain concentrations were then simulated at two dosing regimens (4 g every 6 h or 8 h), and the time over the MICs (T>MIC) was estimated for breakpoints of susceptible and resistant Streptococcus pneumoniae strains. T>MIC was higher than 90% of the dosing interval for both dosing regimens for susceptible strains and only for 4 g every 6 h for resistant ones. In conclusion, brain distribution of cefotaxime was well described by microdialysis in patients and was limited.
authors.affiliation: Inserm U1070, Pole Biologie Santé, Poitiers, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dahyot-Fizelier
authors.forename: Denis
authors.initials: D
authors.lastname: Frasca
authors.forename: Nicolas
authors.initials: N
authors.lastname: Grégoire
authors.forename: Christophe
authors.initials: C
authors.lastname: Adier
authors.forename: Olivier
authors.initials: O
authors.lastname: Mimoz
authors.forename: Bertrand
authors.initials: B
authors.lastname: Debaene
authors.forename: William
authors.initials: W
authors.lastname: Couet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchand
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002439:Cefotaxime / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D002439:Cefotaxime