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Intracellular penetration and antimicrobial activity of antibiotics
Abstract:
Delayed response or recurrence of clinical infections may, in part, be due to the inability of certain antibiotics to penetrate human polymorphonuclear leukocytes (PMN) and exert intracellular antibacterial activity. We determined the penetration of PMN by certain hydrophilic and certain lipophilic antibiotics, and assessed their activity against intracellular Haemophilus influenzae, type b or Staphylococcus aureus. We found that penicillin G was excluded from human PMN while chloramphenicol was concentrated within these cells; chloramphenicol killed significantly more intracellular H. influenzae than did penicillin or ampicillin. Clindamycin and trimethoprim penetrated into normal and chronic granulomatous disease (CGD) PMN equally and were at least transiently concentrated in the cells. Clindamycin and the combinations trimethoprim/sulphamethoxazole and trimethoprim/rifampicin were most effective in killing intracellular Staph. aureus in vitro; these antibiotics reduced the bacterial density in CGD PMN to values comparable to those in normal PMN. The mechanism by which clindamycin and rifampicin killed intracellular Staph. aureus appeared to be due to direct antimicrobial activity. Antibiotics that penetrate into phagocytes may be more effective in infections due to pathogens capable of intracellular survival.
Insights
Certain antibiotics effectively kill bacteria inside human immune cells (polymorphonuclear leukocytes, or PMN). Antibiotic penetration into PMN is key for treating intracellular infections caused by bacteria like Staphylococcus aureus.
Area of Science:
- Pharmacology
- Microbiology
- Immunology
Background:
- Delayed infection response can stem from antibiotics failing to enter human polymorphonuclear leukocytes (PMN).
- Intracellular bacteria pose a treatment challenge if antibiotics cannot reach them within host cells.
Purpose of the Study:
- To evaluate the penetration of various antibiotics into human PMN.
- To assess the intracellular antibacterial activity of these antibiotics against Haemophilus influenzae and Staphylococcus aureus.
Main Methods:
- Determined antibiotic penetration into PMN (normal and CGD).
- Assessed activity against intracellular H. influenzae and S. aureus.
- Measured bacterial density reduction post-antibiotic treatment.
Main Results:
- Penicillin G was excluded from PMN; chloramphenicol concentrated within cells, effectively killing intracellular H. influenzae.
- Clindamycin and trimethoprim penetrated PMN, with clindamycin, trimethoprim/sulphamethoxazole, and trimethoprim/rifampicin showing efficacy against intracellular S. aureus.
- Antibiotics like clindamycin and rifampicin demonstrated direct antimicrobial activity against intracellular S. aureus.
Conclusions:
- Antibiotic penetration into phagocytic cells like PMN is crucial for effective treatment of intracellular bacterial infections.
- Specific antibiotics, including chloramphenicol, clindamycin, and trimethoprim combinations, show promise for targeting intracellular pathogens.