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Penetration into tissues of various drugs active against gram-positive bacteria
1Department of Hospital Epidemiology, University Hospital, Freiburg, FRG.
Abstract:
Gram-positive bacteria are the most important pathogens causing hospital- and community-acquired infections. We therefore reviewed the penetration of various antibiotics active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus into tissues, where staphylococcal infections are common. Rifampicin reaches heart valve concentrations of 65% of the simultaneous serum levels. At 8 h after administration blood and tissues concentrations of rifampicin exceeded the MIC90 values for S. aureus as well as for S. epidermidis. After a 2-g intravenous bolus injection of flucloxacillin heart valve concentrations exceeded MIC values for staphylococci for more than 8 h whereas subcutaneous and muscle concentrations declined within the same time to undetectable levels. The MIC90 values of vancomycin for S. epidermidis and Enterococcus faecalis are 2.0 and 4.0 mg/l respectively and for S. aureus 1.0 mg/l. This concentration is reached in subcutaneous tissue, heart valves and muscle for at least 4-6 h after administration of 15 mg/kg, however the corresponding value for Enterococcus faecalis in heart valve is maintained only for 3-4 h. After two and three dose regimens of teicoplanin serum and bone levels were significantly higher than fat levels, exceeding the MIC90 values for S. aureus, S. epidermidis and E. faecalis. The ratio of tissue concentration of teicoplanin to serum concentrations was 11% for fat and 65% for bone.
Insights
Antibiotic penetration into infection sites is crucial for treating Gram-positive bacterial infections. Rifampicin, flucloxacillin, vancomycin, and teicoplanin show varied tissue distribution, impacting efficacy against pathogens like Staphylococcus aureus.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Gram-positive bacteria are leading causes of hospital and community infections.
- Understanding antibiotic penetration into tissues is vital for treating staphylococcal infections.
Purpose of the Study:
- To review antibiotic penetration into tissues for Gram-positive pathogens.
- To compare tissue concentrations of rifampicin, flucloxacillin, vancomycin, and teicoplanin against relevant minimum inhibitory concentrations (MICs).
Main Methods:
- Review of existing literature on antibiotic tissue penetration.
- Analysis of drug concentrations in heart valves, subcutaneous tissue, muscle, bone, and fat.
- Comparison of achieved tissue concentrations with MIC90 values for key Gram-positive bacteria.
Main Results:
- Rifampicin achieved 65% of serum levels in heart valves and exceeded MIC90 for S. aureus and S. epidermidis for 8 hours.
- Flucloxacillin maintained heart valve concentrations above MIC for >8 hours, but levels in muscle and subcutaneous tissue declined rapidly.
- Vancomycin and teicoplanin achieved concentrations exceeding MIC90 for S. aureus, S. epidermidis, and E. faecalis in various tissues for several hours, with bone levels being significantly higher than fat levels for teicoplanin.
Conclusions:
- Antibiotic penetration into infection sites varies significantly among drugs.
- Rifampicin and flucloxacillin show good heart valve penetration, while vancomycin and teicoplanin demonstrate broad tissue coverage.
- Optimizing antibiotic selection based on tissue penetration is essential for effective treatment of Gram-positive bacterial infections.