title: Interpretation of middle ear fluid concentrations of antibiotics: comparison between ceftibuten, cefixime and azithromycin.
abstract: OBJECTIVE
  The aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media.
  
  
  METHODS
  This randomized, open study compared the penetration of ceftibuten (9 mg kg(-1) 18 patients), cefixime (8 mg kg(-1), 16 patients) and azithromycin (10 mg kg(-1) 16 patients) into the intracellular and extracellular compartments of middle ear fluid of 50 paediatric patients (aged 8-14 years) with acute otitis media. Middle ear fluid was extracted by tympanocentesis 4, 12 and 24 h after dosing and divided into two fractions: with cells (as collected) (C+) and cell-free (C-). Antibiotics were assayed in C+ and C- samples by h.p.l.c.
  
  
  RESULTS
  Ceftibuten achieved greater penetration into middle ear fluid than cefixime and azithromycin. Higher concentrations of ceftibuten (CTB) and cefixime (CFX) were found in the C- fraction (CTB: 4h 13.3+/-1.86; 12h 4.7+/-1.18; 24h 0.5+/-0.2. CFX: 4h 3.2+/-1.4; 12h 1.5+/-0.5; 24h>(0.1 mgl(-1)) than in the C+ fraction (CTB:4 h 8.4+/-4.3; 12 h 2.88+/-1.19; 24 h 0.3+/-0.27. CFX: 4 h 1.2+/-0.6; 12 h 0.8+/-0.2; 24 h>0.1 mg l(-1)) at the each time point, while the opposite was true for azithromycin (C-: 4 h 0.11+/-0.04; 12 h 0.12+/-0.08; 24 h 0.23+/-0.12. C+: 4 h 0.38+/-0.24; 12 h 0.9+/-0.03; 24 h 1.05+/-0.3 mg l(-1)).
  
  
  CONCLUSIONS
  This study demonstrates that the penetration of antibiotics into the middle ear fluid is influenced by its serum concentrations as well as by the cell content in the fluid. Ceftibuten achieved higher middle ear fluid concentrations than cefixime in C+ and C- fractions at all time points. Both ceftibuten and cefixime concentrations are negatively influenced by the cell content in the fluid. In contrast the concentration of azithromycin to the middle ear fluid is positively influenced by the cell content in the fluid.
authors.affiliation: Department of Pharmacology, University of Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scaglione
authors.forename: G
authors.initials: G
authors.lastname: Demartini
authors.forename: S
authors.initials: S
authors.lastname: Dugnani
authors.forename: M M
authors.initials: MM
authors.lastname: Arcidiacono
authors.forename: J P
authors.initials: JP
authors.lastname: Pintucci
authors.forename: F
authors.initials: F
authors.lastname: Fraschini
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017963:Azithromycin / Q000493:pharmacokinetics / Q000627:therapeutic use; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077722:Ceftibuten; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017963:Azithromycin; D020682:Cefixime; D000077722:Ceftibuten; D002439:Cefotaxime