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Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes
Abstract:
A uniformly fatal, reproducible model of experimental meningitis due to Listeria monocytogenes was developed in rabbits for study of the natural progression of the disease and was used to evaluate treatment regimens. Bacterial titers in cerebrospinal fluid and pleocytosis approximated those found in humans. Therapeutic studies in vivo revealed that rifampin was less rapidly bactericidal than ampicillin or penicillin, the agents usually recommended for treatment of meningitis; that penicillin plus rifampin was no more efficacious than penicillin alone; that ampicillin demonstrated greater bactericidal activity in vivo than did penicillin; and that addition of an aminoglycoside (gentamicin) to either penicillin or ampicillin significantly enhanced their bactericidal activity in vivo. Ampicillin plus gentamicin was the most effective combination in vivo and may represent the preferred mode of therapy for listeria meningitis.
Insights
Researchers developed a rabbit model for Listeria monocytogenes meningitis. Ampicillin combined with gentamicin proved most effective, suggesting a preferred treatment for this serious bacterial meningitis.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Listeria monocytogenes can cause severe meningitis.
- Effective treatment regimens for listeria meningitis require further investigation.
- A reproducible animal model is crucial for evaluating therapeutic strategies.
Purpose of the Study:
- To develop and validate a rabbit model of experimental Listeria monocytogenes meningitis.
- To evaluate the in vivo efficacy of various antimicrobial agents and combinations against Listeria meningitis.
- To identify the most effective treatment regimen for Listeria meningitis.
Main Methods:
- Development of a uniformly fatal, reproducible rabbit model of Listeria monocytogenes meningitis.
- Quantification of bacterial titers in cerebrospinal fluid and assessment of pleocytosis.
- In vivo therapeutic studies comparing ampicillin, penicillin, rifampin, and gentamicin, alone and in combination.
Main Results:
- The rabbit model closely mimicked human Listeria meningitis parameters (bacterial titers, pleocytosis).
- Ampicillin exhibited greater in vivo bactericidal activity than penicillin.
- Rifampin was less bactericidal than ampicillin or penicillin.
- Combination therapy with an aminoglycoside (gentamicin) significantly enhanced the bactericidal activity of penicillin or ampicillin.
- Ampicillin plus gentamicin demonstrated the highest in vivo efficacy.
Conclusions:
- The developed rabbit model is suitable for studying Listeria meningitis and evaluating treatments.
- Ampicillin is more effective than penicillin in this model.
- Combination therapy with ampicillin and gentamicin is highly effective and may be the preferred treatment for Listeria meningitis.