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Interactions of dirithromycin with human polymorphonuclear leukocytes

W L Hand1, D L Hand

  • 1Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303.

Antimicrobial Agents and Chemotherapy
|December 1, 1993
PubMed
Summary
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Dirithromycin, a macrolide antibiotic, is highly concentrated in human phagocytic cells (polymorphonuclear leukocytes). This prolonged retention may enhance drug delivery to infection sites and aid in bacterial killing.

Area of Science:

  • Pharmacology
  • Microbiology
  • Cell Biology

Background:

  • Macrolide antibiotics exhibit high tissue concentrations.
  • Certain macrolides concentrate within phagocytic cells.
  • Dirithromycin is a novel macrolide antibiotic.

Purpose of the Study:

  • To investigate the interaction between dirithromycin and human polymorphonuclear leukocytes (PMNs).
  • To determine dirithromycin's cellular uptake, retention, and impact on PMN function.

Main Methods:

  • Utilized radiolabeled dirithromycin and velocity-gradient centrifugation to quantify PMN uptake (C/E ratio).
  • Assessed uptake dependency on cell viability, temperature, pH, and microbial particle ingestion.
  • Evaluated dirithromycin's effect on PMN respiratory burst and bacterial killing.

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Main Results:

  • Dirithromycin was avidly accumulated by PMNs, with C/E ratios reaching 35 at 2 hours.
  • Uptake was dependent on cell viability, temperature, and pH (optimum 8.6).
  • Dirithromycin exhibited slow efflux from PMNs and inhibited the respiratory burst but enhanced Staphylococcus aureus killing.

Conclusions:

  • Dirithromycin demonstrates significant accumulation and prolonged retention within human PMNs.
  • These cellular interactions suggest a potential role in delivering antibiotics to infection sites and augmenting host defense mechanisms.
  • Dirithromycin's effects on PMN function may contribute to both intra- and extracellular bacterial killing.