Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils

G L Mandell1, E Coleman

  • 1Division of Infectious Diseases, University of Virginia Health System, Charlottesville, Virginia 22908-1341, USA. gm@virginia.edu

Insights

Certain antibiotics, including azithromycin and fluoroquinolones, are concentrated and transported by polymorphonuclear neutrophils (PMN). These PMN-delivered antibiotics effectively inhibit bacterial growth at infection sites.

Area of Science:

  • Microbiology
  • Immunology
  • Pharmacology

Background:

  • Polymorphonuclear neutrophils (PMN) migrate to infection sites.
  • Antimicrobial agents need to enter and be transported by PMN without altering migration to be effective.
  • Penicillin G was found to be ineffective as it did not enter or get transported by PMN.

Purpose of the Study:

  • To investigate the cellular uptake, transport, and release of specific antibiotics by PMN.
  • To determine if certain antibiotics can be effectively delivered to infection sites via PMN.

Main Methods:

  • PMN were exposed to various antibiotics.
  • Antibiotic concentration within PMN was measured.
  • PMN migration towards a chemoattractant in the presence of antibiotics was assessed.
  • Antibiotic release from PMN and subsequent bacterial growth inhibition were evaluated.

Main Results:

  • Azithromycin, ciprofloxacin, levofloxacin, moxifloxacin, and telithromycin were concentrated within PMN.
  • These antibiotics were transported by PMN towards a chemoattractant.
  • The antibiotics were released from PMN and demonstrated inhibitory effects on bacterial growth.

Conclusions:

  • Several key antibiotics are effectively internalized, transported, and released by PMN.
  • PMN can serve as a delivery mechanism for these antimicrobial agents to infection sites.
  • This mechanism holds potential for enhancing antimicrobial efficacy in treating infections.

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