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The postantibiotic effect of fusidic acid against gram-positive bacteria
1Department of Microbiology and Infectious Diseases, Monash Medical Centre, Melbourne, Victoria, Australia.
Abstract:
The in-vitro postantibiotic effect (PAE) of fusidic acid was tested for six strains of Staphylococcus aureus and four strains of Streptococcus pyogenes. The maximum PAE that could be achieved was more than 3 h, but at concentrations of antibiotic attainable in humans, the PAE was less than 2 h. Additional experiments were performed in albumin, to examine the effect of the strong protein binding of fusidic acid on the MIC and PAE. MICs were increased, but at the same multiple of the MIC, PAEs were similar to those performed in Mueller-Hinton broth.
Insights
Fusidic acid exhibits a postantibiotic effect (PAE) against Staphylococcus aureus and Streptococcus pyogenes. However, clinically achievable concentrations result in a shorter PAE, potentially impacting treatment efficacy.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Fusidic acid is a key antibiotic for treating Staphylococcus aureus infections.
- Understanding the postantibiotic effect (PAE) is crucial for optimizing antibiotic dosing strategies.
- Protein binding can significantly influence antibiotic efficacy and pharmacokinetic/pharmacodynamic (PK/PD) parameters.
Purpose of the Study:
- To determine the in vitro postantibiotic effect (PAE) of fusidic acid against Staphylococcus aureus and Streptococcus pyogenes.
- To investigate the impact of protein binding on fusidic acid's minimum inhibitory concentration (MIC) and PAE.
- To evaluate the clinical relevance of fusidic acid's PAE at human-attainable concentrations.
Main Methods:
- In vitro susceptibility testing including MIC determination.
- Postantibiotic effect (PAE) assays were performed on bacterial isolates.
- Experiments were conducted in Mueller-Hinton broth and albumin-supplemented media to simulate physiological conditions.
Main Results:
- Fusidic acid demonstrated a maximum in vitro PAE exceeding 3 hours.
- At concentrations achievable in humans, the PAE was less than 2 hours.
- Protein binding to albumin increased MIC values but did not alter PAE when expressed as a multiple of the MIC.
Conclusions:
- The clinical efficacy of fusidic acid may be limited by its short PAE at therapeutic concentrations.
- Protein binding influences fusidic acid's MIC but not its PAE normalized to the MIC.
- Further research is needed to optimize fusidic acid dosing regimens for effective treatment of bacterial infections.