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

Abstract

Through alterations primarily in the penicillin-binding proteins, a non-beta-lactamase-mediated resistance to beta-lactams has evolved in Haemophilus influenzae. The virulence of these chromosomally changed strains has been questioned. To ascertain whether these alterations involve 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 with a susceptible recipient strain or a genetically similar resistant transformant strain. Antibiotic therapy was started on day 3 after inoculation, and the animals were monitored by daily otomicroscopy and analysis of bacterial samples from middle ear effusions obtained on day 8, the 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 was delayed, and the late structural changes were more severe in the animals challenged with the latter strain. The results of the study indicate that chromosomal alterations mediating a relatively low level of resistance to beta-lactams may be advantageous for H. influenzae during antibiotic treatment of a local infection in the rat, and the alterations may occur without any significant loss of virulence.

A novel PBP3 substitution in Haemophilus influenzae confers reduced aminopenicillin susceptibility

“…For site-directed mutagenesis, a well-characterized, β-lactam-susceptible isolate (NTHi3655) previously kindly donated by R. Munson, St Louis, Mo., was chosen [ 12 ]. This strain was chosen since its full genome sequence is known and it has a wtPBP3 sequence identical to that of H.influenzae Rd.…”

Intra‐ and interstrain differences of virulence among nontypeable Haemophilus influenzae strains

“…1). NTHi strain 772 and other strains with LPS immunoreactivity similar to that of strain 3655 (see Table 2) were not included in the dose-finding series, as these strains had previously been shown to have a dose requirement above lo6 cfdml (21,22). In addition, animals (n=2X6) were challenged with hemadsorption-positive and -negative variants of animalpassaged strain 6-173 at a concentration of lo5 c f d ml.…”