Open AccessRelative effectiveness of azithromycin in killing intracellular Porphyromonas gingivalis
Author(s) -
Lai PinChuang,
Walters John D.
Publication year - 2016
Publication title -
clinical and experimental dental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.464
H-Index - 9
ISSN - 2057-4347
DOI - 10.1002/cre2.17
Subject(s) - porphyromonas gingivalis , microbiology and biotechnology , azithromycin , medicine , intracellular , periodontitis , pharmacology , chemistry , antibiotics , biology , biochemistry
Invasive infections by Porphyromonas gingivalis are associated with persistent periodontal attachment loss and can be difficult to eliminate by scaling and root planing. Azithromycin (AZM) inhibits P . gingivalis and is actively accumulated by most human cells. We used an in vitro infection model to compare the effectiveness of AZM in killing intracellular P . gingivalis to the combined regimen of amoxicillin (AMX) and metronidazole (MET). Transport of [ 3 H]‐AZM by human gingival fibroblasts was characterized. Monolayers of Smulow–Glickman gingival epithelial cells or gingival fibroblasts were infected with P . gingivalis (strain 33277 or W83). After extracellular bacteria were eliminated with teicoplanin, infected cells were treated with therapeutic concentrations of AZM, AMX, or AMX + MET. Viable intracellular bacteria were released by cell lysis and plated on blood agar for enumeration. Antimicrobial activity against planktonic P . gingivalis was also evaluated. While survival of intraepithelial P . gingivalis 33277 was not significantly different after treatment with the three regimens, survival in infected fibroblasts was significantly lower after AZM treatment (65.9 ± 5.5%) compared with AMX (92.2 ± 3.5%) or AMX + MET (79.8 ± 5.2%, P < 0.01). Carnitine, a competitive inhibitor of AZM transport, reduced killing by AZM by ~55% ( P < 0.05). Survival of intrafibroblast P . gingivalis W83 was also significantly lower after AZM treatment compared with the other regimens ( P < 0.05). At therapeutic concentrations, AZM was significantly more active against intracellular P . gingivalis than against planktonic P . gingivalis ( P < 0.0083). Gingival epithelial cells and fibroblasts possess a transport system that accumulates AZM and enhances elimination of intracellular P . gingivalis . Compared with the combination of AMX and MET, AZM was equally effective against intraepithelial P . gingivalis 33277 and significantly more effective against both strains of P . gingivalis from infected gingival fibroblasts. The results suggest that AZM could be a reasonable alternative to the regimen of AMX and MET for periodontal patients who should not take these agents due to known side effects or compliance issues.