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Published on: December 10, 2016
Mouse model for evaluation of antibiotic treatment of acute and chronic infections
1Department of Medical Microbiology, University of Lund, Malmö General Hospital, Sweden.
Abstract:
A thread model is presented which enables the simultaneous evaluation of bactericidal rate and antibiotic concentration at the site of infection in mice. Ampicillin and netilmicin were tested against both gram-positive and gram-negative bacteria. With the doses tested there was substantial drug penetration into the site of infection immediately after initiation of infection (day 0), whereas the drug penetration on days 2 and 6 of infection was delayed and reduced. On day 0 of infection there was significant bactericidal effect, but little or no effect could be demonstrated on days 2 and 6 of infection, even though drug concentrations close to the MBC values for several drug/bacteria combinations were reached. The model reflects the treatment situations for the acute and the chronic infection and may be of help in evaluating the efficacy of the drug at the site of infection.
Insights
A new thread model evaluates bactericidal rate and antibiotic concentration at infection sites in mice. It found early infection (day 0) showed good drug penetration and bacterial killing, unlike later stages (days 2 and 6).
Area of Science:
- Pharmacology
- Infectious Diseases
- Animal Models
Background:
- Evaluating antibiotic efficacy at infection sites is crucial for treatment.
- Acute and chronic infections present different challenges for drug delivery and effectiveness.
- Existing models may not fully capture the dynamic interplay between antibiotic concentration and bacterial response in vivo.
Purpose of the Study:
- To present a novel thread model for simultaneous evaluation of bactericidal rate and antibiotic concentration.
- To assess the penetration and efficacy of ampicillin and netilmicin against Gram-positive and Gram-negative bacteria in a murine infection model.
- To compare drug performance in acute (day 0) versus chronic (days 2 and 6) infection settings.
Main Methods:
- Development and application of a thread model in mice to monitor infection sites.
- Administration of ampicillin and netilmicin.
- Measurement of antibiotic concentrations and bactericidal rates at days 0, 2, and 6 post-infection.
- Testing against both Gram-positive and Gram-negative bacteria.
Main Results:
- Substantial antibiotic penetration and significant bactericidal effect were observed immediately after infection (day 0).
- Delayed and reduced antibiotic penetration occurred on days 2 and 6 of infection.
- Limited or no bactericidal effect was demonstrated on days 2 and 6, despite achieving concentrations near the minimum bactericidal concentration (MBC).
Conclusions:
- The thread model effectively reflects acute and chronic infection scenarios.
- Antibiotic efficacy at the infection site is significantly reduced in later stages of infection.
- This model can aid in evaluating drug efficacy in vivo, particularly for infections with delayed treatment.
- Early intervention is critical for optimal antibiotic effectiveness at the infection site.
