AMOXICILLIN TREATMENT OF EXPERIMENTAL ACUTE OTITIS-MEDIA CAUSED BY HAEMOPHILUS-INFLUENZAE WITH NON-BETA-LACTAMASE-MEDIATED RESISTANCE TO BETA-LACTAMS - ASPECTS OF VIRULENCE AND TREATMENT

Through alterations primarily in the penicillin-binding proteins, a no n-beta-lactamase-mediated resistance to beta-lactams has evolved in Ha emophilus influenzae. The virulence of these chromosomally changed str ains has been questioned. To ascertain whether these alterations invol ve a reduction in virulence of H. influenzae and;whether they could be advantageous for the bacterium during amoxicillin treatment of acute otitis media, a total of 70 Sprague-Dawley rats were challenged,vith a susceptible recipient strain or a genetically similar resistant trans :formant strain. Antibiotic therapy was started on day 3 after inocula tion, and the animals were monitored by daily otomicroscopy and analys is of bacterial samples from middle ear effusions obtained on day 8, t he last day of observation, The animals were also Sacrificed on days 4 and 8 and after 2 months for morphological examination, Compared with the susceptible recipient strain, recovery from infections caused by the resistant transformant strain,vas delayed, and the late structural changes were more severe in the animals challenged with the latter st rain. The results of the study indicate that chromosomal alterations m ediating a relatively low level of resistance to beta-lactams may be a dvantageous for H. influenzae during antibiotic treatment of a local i nfection in the rat, and the alterations may occur without any signifi cant loss of virulence.