Relative effectiveness of azithromycin in killing intracellular Porphyromonas gingivalis.

Invasive infections by are associated with persistent periodontal attachment loss and can be difficult to eliminate by scaling and root planing. Azithromycin (AZM) inhibits .  and is actively accumulated by most human cells. We used an in vitro infection model to compare the effectiveness of AZM in killing intracellular .  to the combined regimen of amoxicillin (AMX) and metronidazole (MET). Transport of [H]-AZM by human gingival fibroblasts was characterized. Monolayers of Smulow-Glickman gingival epithelial cells or gingival fibroblasts were infected with .  (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 .  was also evaluated. While survival of intraepithelial .  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%,  < 0.01). Carnitine, a competitive inhibitor of AZM transport, reduced killing by AZM by ~55% ( < 0.05). Survival of intrafibroblast .  W83 was also significantly lower after AZM treatment compared with the other regimens ( < 0.05). At therapeutic concentrations, AZM was significantly more active against intracellular .  than against planktonic .  ( < 0.0083). Gingival epithelial cells and fibroblasts possess a transport system that accumulates AZM and enhances elimination of intracellular . . Compared with the combination of AMX and MET, AZM was equally effective against intraepithelial .  33277 and significantly more effective against both strains of .  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.