title: Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae.
abstract: OBJECTIVE
  To evaluate the effect of delayed administration of erythromycin in the course of acute otitis media caused by an erythromycin-susceptible Streptococcus pneumoniae strain in the gerbil model.
  
  
  METHODS
  The bacterium was inoculated by transbullar challenge in the middle ear (ME) and antibiotic treatment at different doses was administered at various times thereafter.
  
  
  RESULTS
  When 2.5 mg/kg of erythromycin was administered as a single dose 2, 5, 18 or 21 h post-inoculation (pi) the bacterial eradication rate was 55, 40, 0 and 0%, respectively. A higher dose (5 mg/kg) administered also as a single dose 2, 5, 18 and 21 h pi achieved bacterial eradication rates of 62.5, 43.8, 0 and 0%, respectively. Using a very high dose (50 mg/kg) repeated three times at 3 h intervals (total dose 150 mg/kg) and starting the treatment 21 h pi only achieved bacterial eradication in 25% of cases. The concentration of erythromycin achieved in the ME 90 min after administration of 5 mg/kg 5 or 21 h pi was very similar (0.74 and 0.79 mg/L) but the ME half-life was longer (98.2 min) with the early administration as compared with the delayed form (47.5 min), which could partially explain the different results. Further experiments showed that the failures observed with the delayed administration were not related to the time elapsed from antibiotic administration to ME sampling or selection of antibiotic-resistant mutants.
  
  
  CONCLUSIONS
  Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.
authors.affiliation: Unit for Research in Medical Microbiology and Antimicrobial Chemotherapy, Otolaryngology, and Epidemiology, Fundación Jiménez Díaz--UTE, Avenida de Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Carmina
authors.initials: C
authors.lastname: Martínez-Marín
authors.forename: Lorena
authors.initials: L
authors.lastname: Huelves
authors.forename: Gema
authors.initials: G
authors.lastname: del Prado
authors.forename: José I
authors.initials: JI
authors.lastname: García-Cía
authors.forename: Carlos
authors.initials: C
authors.lastname: Cenjor
authors.forename: Carmen
authors.initials: C
authors.lastname: Ponte
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Granizo
authors.forename: Francisco
authors.initials: F
authors.lastname: Soriano
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005849:Gerbillinae; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000188:drug therapy*; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin