Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy
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Abstract:
A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.
Insights
This study developed a rabbit model for Haemophilus influenzae type b meningitis, revealing host factors influencing infection. Aztreonam treatment significantly reduced mortality in established meningitis.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Haemophilus influenzae type b (Hib) is a major cause of bacterial meningitis.
- Understanding Hib pathogenesis and effective treatment is crucial.
Purpose of the Study:
- To develop an infant rabbit model for studying Hib meningitis.
- To investigate factors influencing Hib colonization and infection.
- To evaluate the efficacy of aztreonam in treating established Hib meningitis.
Main Methods:
- Infant rabbits were infected intranasally with Hib.
- Nasopharyngeal mucosa was pretreated with trypsin or saline.
- Bacteremia and meningitis development were monitored.
- Aztreonam pharmacokinetics in cerebrospinal fluid (CSF) were assessed.
- Mortality rates were compared between treated and untreated groups.
Main Results:
- The rabbit model mimicked human Hib meningitis, with high mortality.
- Nasopharyngeal pretreatment increased bacteremia rates.
- Aztreonam achieved 6-7% serum concentration in infected CSF, versus 2-3% in normal CSF.
- Aztreonam reduced mortality from 88% to 9% in established meningitis.
Conclusions:
- Host factors on respiratory epithelial cells influence Hib colonization.
- The rabbit model is valuable for studying Hib meningitis.
- Aztreonam is highly effective in treating established Hib meningitis in this model.