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Effect of several antimicrobial agents on ciprofloxacin uptake by human neutrophils
Abstract:
The effect of antimicrobial agent active against anaerobes, gram-positive cocci and fungi on the uptake of ciprofloxacin by human neutrophils (PMNs) was evaluated. In the presence of therapeutic extracellular concentrations of these agents, ciprofloxacin reached high intracellular concentrations [cellular-to-extracellular ratio (C/E) greater than or equal to 2.9], this value being higher in the presence of amphotericin B (C/E 6.3 +/- 0.9). The intracellular penetration of ciprofloxacin was higher when PMNs were stimulated with opsonized zymosan (C/E greater than or equal to 5.6). In summary, none of the antimicrobial agents tested significantly impaired the uptake of ciprofloxacin by human PMNs.
Insights
Ciprofloxacin uptake by human neutrophils (PMNs) was unaffected by common antimicrobial agents. High intracellular concentrations were achieved even with concurrent therapy, indicating no significant drug interaction.
Area of Science:
- Pharmacology
- Microbiology
- Immunology
Background:
- Ciprofloxacin is a widely used fluoroquinolone antibiotic.
- Neutrophils (PMNs) are critical immune cells involved in fighting infections.
- Potential interactions between ciprofloxacin and other antimicrobial agents affecting PMN function are not fully understood.
Purpose of the Study:
- To evaluate the impact of antimicrobial agents targeting anaerobes, gram-positive cocci, and fungi on ciprofloxacin uptake by human neutrophils.
- To determine if co-administration of these agents affects intracellular ciprofloxacin concentrations in PMNs.
Main Methods:
- Human neutrophils (PMNs) were incubated with ciprofloxacin in the presence of various antimicrobial agents.
- Intracellular and extracellular concentrations of ciprofloxacin were measured using a cellular-to-extracellular ratio (C/E).
- PMN stimulation with opsonized zymosan was used to assess uptake under inflammatory conditions.
Main Results:
- Ciprofloxacin achieved high intracellular concentrations (C/E ≥ 2.9) in human PMNs, even with co-administered antimicrobial agents.
- The presence of amphotericin B resulted in higher ciprofloxacin intracellular concentrations (C/E = 6.3 ± 0.9).
- Stimulation of PMNs with opsonized zymosan enhanced ciprofloxacin intracellular penetration (C/E ≥ 5.6).
- None of the tested antimicrobial agents significantly impaired ciprofloxacin uptake by PMNs.
Conclusions:
- Concurrent administration of common antimicrobial agents does not significantly hinder ciprofloxacin's intracellular accumulation in human neutrophils.
- Amphotericin B may enhance ciprofloxacin uptake into PMNs.
- These findings suggest favorable pharmacokinetic profiles for combination therapies involving ciprofloxacin and the evaluated antimicrobial agents.