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Free radical production by antibiotic-killed bacteria in the guinea pig middle ear
1Department of Otolaryngology--Head and Neck Surgery, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Objectives:
Oxygen free radicals are implicated in the pathogenesis of otitis media Recent investigations with animal models have demonstrated that free radical-mediated damage of the middle ear mucosa, measured as lipid hydroperoxide, occurs when the middle ear cavity is inoculated with Streptococcus pneumoniae. The present study was conducted to examine the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media.
Study Design:
Animal model of acute otitis media.
Methods:
Seventy-eight guinea pigs underwent bilateral middle ear inoculation with 100 microl of 1) sterile saline as a control, 2) 50 microg/mL amoxicillin, 3) 10(7) colony forming units (CFU)/mL Streptococcus pneumoniae killed with 50 microg/mL amoxicillin, or 4) 10(7) CFU/mL S. pneumoniae. Animals were killed on postoperative day 1 or 5, and the middle ear mucosa was examined for lipid peroxidation as evidence of free radical damage.
Results:
Mucosal lipid hydroperoxide was significantly elevated compared with control subjects on day 1 in both the antibiotic-killed S. pneumoniae group and the S. pneumoniae-infected group. On day 5, the S. pneumoniae-infected mucosa had significantly higher lipid hydroperoxide levels compared with the antibiotic-killed group and the control subjects. Histological studies confirmed mucosal edema and the presence of inflammatory cells in the infected groups.
Conclusions:
Antibiotic-killed bacteria seem to produce free radical-mediated damage to the middle ear mucosa in the early phase of acute otitis media. The clinical implication of this study is that free radical damage to the middle ear mucosa may occur in otitis media despite appropriate antibiotic therapy.
Insights
Antibiotic-killed Streptococcus pneumoniae can cause free radical damage to the middle ear mucosa in acute otitis media. This damage may occur even with antibiotic treatment, highlighting the role of free radicals in otitis media pathogenesis.
Area of Science:
- Otorhinolaryngology
- Microbiology
- Biochemistry
Background:
- Oxygen free radicals are implicated in otitis media pathogenesis.
- Animal models show Streptococcus pneumoniae inoculation causes middle ear mucosal damage.
- Lipid hydroperoxide levels indicate free radical damage.
Purpose of the Study:
- To investigate the effect of antibiotics on free radical-mediated damage in pneumococcal acute otitis media.
Main Methods:
- Seventy-eight guinea pigs were used in an animal model of acute otitis media.
- Middle ear inoculation included sterile saline, amoxicillin, antibiotic-killed S. pneumoniae, and live S. pneumoniae.
- Middle ear mucosa was analyzed for lipid peroxidation on postoperative days 1 and 5.
Main Results:
- Lipid hydroperoxide levels were elevated in both antibiotic-killed and infected groups on day 1.
- On day 5, S. pneumoniae-infected mucosa showed significantly higher lipid hydroperoxide levels than the antibiotic-killed and control groups.
- Histology confirmed mucosal edema and inflammatory cell infiltration in infected groups.
Conclusions:
- Antibiotic-killed bacteria may induce free radical damage in the early stages of acute otitis media.
- Free radical damage to the middle ear mucosa can occur in otitis media despite antibiotic therapy.