title: Azithromycin enhances phagocytic killing of Aggregatibacter actinomycetemcomitans Y4 by human neutrophils.
abstract: BACKGROUND
  Aggregatibacter actinomycetemcomitans resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of A. actinomycetemcomitans by neutrophils.
  
  
  METHODS
  Killing assays were conducted in the presence of either 2 μg/mL AZM or 16 μg/mL AMX (equipotent against A. actinomycetemcomitans). Neutrophils were loaded by incubation with the appropriate antibiotic. Opsonized A. actinomycetemcomitans strain Y4 was incubated with the indicated antibiotic alone, with loaded neutrophils and antibiotic, or with control neutrophils (without antibiotic) at multiplicities of infection (MOIs) of 30 and 90 bacteria per neutrophil.
  
  
  RESULTS
  Neutrophil incubation with 2 μg/mL AZM yielded an intracellular concentration of 10 μg/mL. At an MOI of 30, neutrophils loaded with AZM failed to kill significantly more bacteria than control neutrophils during the 60- and 90-minute assay periods. At an MOI of 90, neutrophils loaded with AZM killed significantly more bacteria than either AZM alone or control neutrophils during 60- and 90-minute incubations (P < 0.05), and killed significantly more bacteria after 90 minutes than the sum of the killing produced by AZM alone or neutrophils alone. Neutrophils incubated with AMX under identical conditions also killed significantly more bacteria than either AMX alone or control neutrophils, but there was no evidence of synergism between AMX and neutrophils.
  
  
  CONCLUSIONS
  Neutrophils possess a concentrative transport system for AZM that may enhance killing of A. actinomycetemcomitans. Its effects are most pronounced when neutrophils are greatly outnumbered by bacteria.
authors.affiliation: Division of Periodontology, College of Dentistry, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Pin-Chuang
authors.initials: PC
authors.lastname: Lai
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schibler
authors.forename: John D
authors.initials: JD
authors.lastname: Walters
mesh_terms: D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects*; D000658:Amoxicillin / Q000493:pharmacokinetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017963:Azithromycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000502:physiology; D018929:Cell Culture Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D017963:Azithromycin
keywords: Aggregatibacter actinomycetemcomitans; anti-infective agents; immunity; innate; macrolides; neutrophil; periodontitis