Journal of Antimicrobial Chemotherapy (1999) 44, 85-90
© 1999 The British Society for Antimicrobial Chemotherapy
Antimicrobial treatment of an experimental otitis media caused by a ß-lactamase positive isolate of Haemophilus influenzae
a Department of Medical Microbiology; b Department of Otolaryngology, Fundación Jiménez Díaz, Avenida de Reyes Católicos 2, 28040 Madrid; c Medical Department, SmithKline Beecham Pharmaceuticals, Madrid, Spain
A gerbil model of otitis media induced by a ß-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (±10 6 cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses.
* Tel: +33-1-45593219; Fax: +33-1-45593834; E-mail: olivier.mimoz{at}pbr.ap-hop-paris.fr
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