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Antibiotic abscess penetration: fosfomycin levels measured in pus and simulated concentration-time profiles
Robert Sauermann1, Rudolf Karch, Herbert Langenberger
1Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria.
Abstract:
The present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 +/- 64 mg/liter at steady state, exceeding the MIC(50/90)s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, and Escherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 +/- 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.
Insights
Fosfomycin effectively penetrates abscess fluid, with average concentrations exceeding minimum inhibitory concentrations for common abscess-causing bacteria. Higher doses are recommended for optimal therapeutic outcomes in abscess treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Abscesses pose treatment challenges due to potential antibiotic penetration issues.
- Fosfomycin is a broad-spectrum antibiotic with potential utility in complex infections.
Purpose of the Study:
- To evaluate the penetration and concentration of fosfomycin in abscess fluid.
- To determine the pharmacokinetic profile of fosfomycin within abscesses.
- To assess the potential efficacy of fosfomycin for abscess treatment.
Main Methods:
- Twelve patients undergoing abscess drainage received a single intravenous dose of 8g fosfomycin.
- Fosfomycin concentrations were measured in plasma and abscess pus.
- A pharmacokinetic model was used to estimate pus concentration-time profiles.
Main Results:
- Fosfomycin concentrations in abscess fluid varied significantly (undetectable to 168 mg/L).
- Average steady-state concentration in pus was 182 ± 64 mg/L, exceeding MIC50/90 for key pathogens.
- Mean half-life in abscess fluid was exceptionally long (32 ± 39 hours).
Conclusions:
- Fosfomycin demonstrates substantial penetration into abscesses.
- Recommended dosing involves a loading dose (10-12g) followed by 8g thrice daily for effective plasma and pus concentrations.
- This regimen is expected to yield effective fosfomycin levels in abscess fluid for most patients.
