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Uptake and activity of rifapentine in human peritoneal macrophages and polymorphonuclear leukocytes
Abstract:
Rifapentine uptake by human peritoneal macrophages and polymorphonuclear leukocytes was evaluated and its activity against intracellular Staphylococcus aureus and Staphylococcus epidermidis in both types of phagocytes was compared to that of rifampin, teicoplanin and clindamycin. Uptake of radiolabeled rifapentine by peritoneal macrophages (intracellular/extracellular ratio 61.4 +/- 5.8) and polymorphonuclear leukocytes (intracellular/extracellular ratio 87.6 +/- 3.9) was significantly higher than that of teicoplanin (intracellular/extracellular ratio 40.8 +/- 3.6 and 52.3 +/- 3.2 respectively) and clindamycin (intracellular/extracellular ratio 6.9 +/- 0.4 and 8.3 +/- 0.5 respectively). Rifapentine and rifampin showed the highest activity against intracellular staphylococci in both peritoneal macrophages and polymorphonuclear leukocytes. Clindamycin also showed efficient intracellular activity. In contrast, teicoplanin, which achieved high cellular levels with both types of phagocytes, failed to produce a significant reduction in viable intraphagocytic Staphylococcus epidermidis. On the basis of these findings it is suggested that rifapentine may play a future role in the treatment of certain types of staphylococcal infection.
Insights
Rifapentine demonstrated superior uptake and potent activity against intracellular Staphylococcus bacteria in human immune cells compared to other antibiotics. These findings suggest rifapentine
Area of Science:
- Pharmacology
- Microbiology
- Immunology
Background:
- Staphylococcal infections pose significant therapeutic challenges.
- Understanding antibiotic penetration and efficacy within phagocytic cells is crucial for treatment.
- Rifamycins, like rifampin, are known for their activity against intracellular bacteria.
Purpose of the Study:
- To evaluate rifapentine uptake by human peritoneal macrophages and polymorphonuclear leukocytes.
- To compare the activity of rifapentine against intracellular Staphylococcus aureus and Staphylococcus epidermidis with other antibiotics.
- To assess the potential role of rifapentine in treating staphylococcal infections.
Main Methods:
- Radiolabeled rifapentine was used to measure uptake in human peritoneal macrophages and polymorphonuclear leukocytes.
- The intracellular activity of rifapentine, rifampin, teicoplanin, and clindamycin against Staphylococcus was assessed.
- Intracellular to extracellular ratios were calculated to quantify drug uptake.
Main Results:
- Rifapentine showed significantly higher uptake by both macrophages and polymorphonuclear leukocytes compared to teicoplanin and clindamycin.
- Rifapentine and rifampin exhibited the highest activity against intracellular staphylococci in both cell types.
- Teicoplanin failed to significantly reduce viable intraphagocytic Staphylococcus epidermidis despite high cellular levels.
Conclusions:
- Rifapentine possesses excellent intracellular penetration and potent bactericidal activity against staphylococci within human phagocytes.
- Rifapentine's efficacy suggests a promising future role in managing specific staphylococcal infections.
- The study highlights the importance of intracellular antibiotic activity for effective treatment.