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Updated: Jun 7, 2026
PRP as a New Approach to Prevent Infection: Preparation and In vitro Antimicrobial Properties of PRP
Published on: April 9, 2013
Plasma protein binding may reduce antimicrobial activity by preventing intra-bacterial uptake of antibiotics, for
1Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria.
Objectives:
although plasma protein binding (PPB) is accepted to be an essential factor in reducing antimicrobial activity, little is known about the underlying mechanisms. One possibility includes impaired penetration of an antimicrobial into bacterial cells in the presence of PPB. As a prerequisite for testing this hypothesis an optimized medium displaying high protein binding without impairing bacterial growth had to be identified for our model compound clindamycin.
Methods:
determination of PPB, bacterial growth and antimicrobial killing was performed in Mueller-Hinton broth (MHB) containing various amounts of human albumin or serum. [(3)H]clindamycin was used to investigate clindamycin penetration into Staphylococcus aureus.
Results:
of all investigated media only MHB(50%serum) and MHB(70%serum) achieved protein binding comparable to pure serum. In contrast, MHB(20%serum) and most media containing only albumin demonstrated considerably lower protein binding. Pure serum resulted in bacterial growth inhibition compared with MHB while MHB(16%albumin) and MHB(50%serum) did not result in significant differences in bacterial count after 24 h. However, in both MHB(16%albumin) and MHB(50%serum) the antimicrobial activity of clindamycin was reduced by >2 log(10) cfu/mL compared with pure MHB. The radioactive signal after administration of [(3)H]clindamycin to S. aureus was significantly decreased in pure serum as well as in MHB(16%albumin) and MHB(50%serum), while no significant difference was observed for MHB(4%albumin) and MHB(20%serum).
Conclusions:
reduction of the intracellular radioactive signal in the presence of serum proteins correlated both with the degree of protein binding and reduction of antimicrobial activity supporting the hypothesis of impairment of activity by PPB by reducing intra-bacterial antimicrobial concentrations.
Insights
Plasma protein binding (PPB) reduces clindamycin effectiveness by limiting its entry into bacteria. This study identified optimal conditions to investigate this mechanism, confirming PPB impairs antimicrobial activity.
Area of Science:
- Pharmacology
- Microbiology
- Biochemistry
Background:
- Plasma protein binding (PPB) is recognized to decrease antimicrobial efficacy, but the precise mechanisms remain unclear.
- A potential mechanism involves reduced penetration of antimicrobials into bacterial cells due to PPB.
- Investigating this requires a model system with high protein binding that supports bacterial growth.
Purpose of the Study:
- To identify an optimized medium for studying the impact of plasma protein binding on antimicrobial activity.
- To test the hypothesis that PPB impairs antimicrobial efficacy by reducing intracellular drug concentrations.
Main Methods:
- Evaluated protein binding, bacterial growth, and antimicrobial killing in Mueller-Hinton broth (MHB) with varying human albumin or serum concentrations.
- Utilized radiolabeled [(3)H]clindamycin to quantify clindamycin penetration into Staphylococcus aureus.
Main Results:
- MHB with 50% or 70% serum demonstrated protein binding comparable to pure serum.
- MHB containing 16% albumin or 50% serum significantly reduced clindamycin's antimicrobial activity (>2 log(10) cfu/mL) compared to MHB alone.
- Reduced intracellular [(3)H]clindamycin concentrations in S. aureus correlated with increased protein binding and decreased antimicrobial activity.
Conclusions:
- The findings support the hypothesis that plasma protein binding impairs antimicrobial activity.
- This impairment is likely due to reduced intracellular antimicrobial concentrations resulting from PPB.
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