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Pharmacodynamics of antibiotics in fibrin clots
M G Bergeron1, J Robert, D Beauchamp
1Department of Microbiology, Laval University, Québec, Canada.
Abstract:
Fibrin is an integral component of intravascular thrombus, surgical wounds, haematomas, vegetations and foreign bodies which predispose to infection. The tropism that many pathogens have for fibrin may favour bacterial growth and lead to infection. To improve our understanding of the pharmacodynamic interaction between antibiotics and pathogens infecting fibrin clots, this review will: define the role of fibrin as a protective environment for microorganisms; give an historical perspective of in-vitro and in-vivo fibrin clots; describe the pharmacodynamic model of infected fibrin clots; review pharmacodynamic determinants of outcome; and discuss intramicrobial pharmacokinetics. Fibrin clots are hard to penetrate following antibiotic administration and there is a major gradient of concentration from the surface to the core of the clots which has great influence on bacterial growth and lysis. Resistance can develop and morphological and structural changes in bacteria may vary within the different regions of the clot.
Insights
This review explores how fibrin clots protect bacteria from antibiotics. Antibiotic penetration into clots is limited, impacting bacterial growth and potentially leading to resistance.
Area of Science:
- Microbiology
- Pharmacology
- Biomedical Engineering
Background:
- Fibrin is a key component in thrombi, wounds, and foreign bodies, often serving as a niche for microbial colonization.
- Pathogen tropism for fibrin can promote bacterial growth and lead to infections, complicating treatment.
- Understanding the interaction between antibiotics and bacteria within fibrin clots is crucial for effective antimicrobial strategies.
Purpose of the Study:
- To elucidate the role of fibrin as a protective microbial environment.
- To provide a historical overview of in vitro and in vivo fibrin clot models.
- To describe the pharmacodynamic model of antibiotic-antimicrobial interactions within infected fibrin clots.
Main Methods:
- Review of existing literature on fibrin clots, microbial infections, and antibiotic pharmacodynamics.
- Analysis of pharmacodynamic determinants influencing treatment outcomes in infected fibrin clots.
- Discussion of intramicrobial pharmacokinetics and antibiotic concentration gradients within clots.
Main Results:
- Fibrin clots present a significant barrier to antibiotic penetration, creating concentration gradients from the surface to the core.
- These gradients influence bacterial growth, lysis, and the development of antimicrobial resistance.
- Morphological and structural bacterial changes can vary across different regions of the fibrin clot.
Conclusions:
- Fibrin clots create a challenging environment for antibiotic efficacy due to limited penetration and concentration gradients.
- Antimicrobial resistance and bacterial adaptation within clots are influenced by these pharmacodynamic factors.
- Further research into optimizing antibiotic delivery and activity within fibrin clots is warranted.