Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae

• Published in: Journal of antimicrobial chemotherapy 2005-10, Vol.56 (4), p.783-786
• Main Authors: Martínez-Marín, Carmina, Huelves, Lorena, del Prado, Gema, García-Cía, José I., Cenjor, Carlos, Ponte, Carmen, Granizo, Juan J., Soriano, Francisco
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Erythromycin - administration & dosage; Erythromycin - blood; Erythromycin - pharmacokinetics; Erythromycin - therapeutic use; Gerbillinae; gerbils; Medical sciences; Microbial Sensitivity Tests; otitis; Otitis Media - drug therapy; Pharmacology. Drug treatments; pneumococcal; Pneumococcal Infections - drug therapy; Streptococcus pneumoniae; therapy delay; Time Factors; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dki322

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. Conclusion: Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.