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Accumulation and activity of cethromycin (ABT-773) within human polymorphonuclear leucocytes
I García1, A Pascual, S Ballesta
1Department of Microbiology, School of Medicine, Seville, Spain. igarcia1@us.es
The Journal of Antimicrobial Chemotherapy
|June 14, 2003
Summary
Ketolide cethromycin rapidly penetrates human polymorphonuclear leucocytes (PMNs), achieving high intracellular concentrations. This antibiotic demonstrates significant intracellular activity against Staphylococcus aureus within PMNs.
Area of Science:
- Pharmacology
- Microbiology
- Cell Biology
Background:
- Polymorphonuclear leucocytes (PMNs) are critical in combating bacterial infections.
- Understanding intracellular antibiotic penetration is key to optimizing treatment strategies.
Purpose of the Study:
- To assess the cellular uptake and intracellular activity of the ketolide antibiotic cethromycin (ABT-773) in human PMNs.
- To investigate the mechanisms influencing cethromycin penetration into PMNs.
Main Methods:
- Quantified cethromycin uptake in PMNs using radiolabeling and velocity gradient centrifugation.
- Evaluated the activity of intracellular cethromycin against Staphylococcus aureus.
- Assessed the impact of temperature, pH, cell viability, and metabolic inhibitors on cethromycin uptake.
Main Results:
- Cethromycin exhibited a high cellular to extracellular concentration (C/E) ratio (>200) in PMNs, indicating rapid and saturable uptake.
- Intracellular penetration was significantly influenced by temperature, cell viability, pH, and metabolic inhibitors, suggesting an active uptake mechanism.
- Cethromycin demonstrated potent intracellular activity against Staphylococcus aureus at higher concentrations.
Conclusions:
- Cethromycin effectively penetrates human PMNs, reaching high intracellular concentrations.
- The antibiotic retains significant antimicrobial activity within these immune cells, supporting its potential in treating intracellular bacterial infections.