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Antimicrobial Agents and Chemotherapy, September 2004, p. 3536-3542, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3536-3542.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ß-Lactamase-Producing Nontypeable Haemophilus influenzae Fails To Protect Streptococcus pneumoniae from Amoxicillin during Experimental Acute Otitis Media

Department of Oto-Rhino-Laryngology, Umeå University Hospital, Umeå,¹ Department of Medical Microbiology, Malmö University Hospital, Malmö,² Department of Oto-Rhino-Laryngology, Lund University Hospital, Lund, Sweden³

Received 8 July 2003/ Returned for modification 26 November 2003/ Accepted 24 May 2004

Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by ß-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with Streptococcus pneumoniae alone or in combination with ß-lactamase-producing nontypeable Haemophilus influenzae. Amoxicillin was introduced at the clinical peak of the infection. Local and systemic changes were monitored by otomicroscopy, bacterial culture, and analysis of histological changes and the expression of the transforming growth factor beta (TGF-ß) gene. ß-Lactamase-producing H. influenzae did not demonstrate an ability to protect S. pneumoniae. Amoxicillin eradicated the pneumococci in all treated animals but increased to some degree the ability of H. influenzae to persist at the site of infection. Thus, only an insignificant acceleration of the resolution of the AOM caused by a mixture of pathogens was observed during treatment. Moderate to major morphological changes could not be avoided by treatment of the mixed infections, but a slight downregulation of TGF-ß expression was observed. In contrast to infections caused by a single pathogen, the mixed infections induced white plaques in the tympanic membrane at a remarkably high frequency independent of treatment. These experimental findings constitute support for further studies of antimicrobial drugs and AOM caused by bacteria with and without mechanisms of antibiotic resistance.