Uptake of antimicrobial agents by human polymorphonuclear leucocytes

Area of Science:

• Pharmacology
• Cell Biology
• Infectious Diseases

Background:

• Polymorphonuclear leucocytes (PMNs) are crucial in fighting infections.
• Understanding antimicrobial drug penetration into PMNs is vital for effective treatment, especially for intracellular pathogens.

Purpose of the Study:

• To quantify the in vitro uptake of tinidazole, josamycin, and penicillin G by normal human PMNs.
• To assess the potential of these antimicrobials in treating intracellular infections based on their cellular accumulation.

Main Methods:

• Radiolabeled antimicrobial agents were used to measure drug uptake by human PMNs in vitro.
• Extracellular drug concentrations mimicked therapeutically effective serum levels.

Main Results:

• Penicillin G exhibited poor penetration into PMNs, with a cell-to-extracellular concentration ratio (C/E) of 0.23–0.54.
• Tinidazole and josamycin were significantly accumulated by PMNs, with C/E ratios of 1.38–1.56 and 3.5–21.4, respectively.
• High josamycin accumulation was persistent and potentially mediated by active transport.

Conclusions:

• Tinidazole and josamycin accumulate within PMNs, suggesting efficacy against intracellular pathogens.
• These drugs may be valuable for treating chronic infections caused by bacteria that survive intracellularly.
• Josamycin's extensive accumulation points to a potential active transport mechanism in PMNs.