2011
DOI: 10.1902/jop.2010.100221
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Clarithromycin Accumulation by Phagocytes and Its Effect on Killing of Aggregatibacter actinomycetemcomitans

Abstract: Background-Clarithromycin inhibits several periodontal pathogens and is concentrated inside gingival fibroblasts and epithelial cells by an active transporter. We hypothesized that polymorphonuclear leukocytes (PMNs) and less mature myeloid cells possess a similar transporter for clarithromycin. It is feasible that clarithromycin accumulation inside PMNs could enhance their ability to kill Aggregatibacter actinomycetemcomitans.

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Cited by 12 publications
(17 citation statements)
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“…Inhibitors of the P-glycoprotein efflux pump increased the intracellular accumulation of AZM and enhanced the killing of intracellular bacteria. Similarly, PMNs that take up and accumulate CLR exhibit enhanced phagocytic killing of the leukotoxinproducing Y4 strain of A. actinomycetemcomitans (18). Our findings can also be related to a previous study of antibiotic killing of A. actinomycetemcomitans NCTC 9710 within cultured KB epithelial cells (33).…”
Section: Discussionsupporting
confidence: 84%
See 1 more Smart Citation
“…Inhibitors of the P-glycoprotein efflux pump increased the intracellular accumulation of AZM and enhanced the killing of intracellular bacteria. Similarly, PMNs that take up and accumulate CLR exhibit enhanced phagocytic killing of the leukotoxinproducing Y4 strain of A. actinomycetemcomitans (18). Our findings can also be related to a previous study of antibiotic killing of A. actinomycetemcomitans NCTC 9710 within cultured KB epithelial cells (33).…”
Section: Discussionsupporting
confidence: 84%
“…Clarithromycin (CLR), a closely related macrolide, is also actively transported and accumulated by human oral epithelial cells, gingival fibroblasts, and PMNs (17,18). PMNs that have taken up CLR exhibit enhanced phagocytic killing of intracellular A. actinomycetemcomitans (18).…”
mentioning
confidence: 99%
“…A similar study has been conducted with CLR, 21 a macrolide that has a shorter half-life than AZM, is more active against P. gingivalis and Prevotella intermedia , and is comparably effective against A. actinomycetemcomitans . 15,22,32 As with AZM, the most significant differences in killing A. actinomycetemcomitans by control and CLR-loaded neutrophils were observed at a relatively high MOI (100).…”
Section: Discussionmentioning
confidence: 85%
“…However, the transport velocity and the degree of intracellular concentration observed with AZM are lower than those of CLR. 21 In spite of this, the results suggest that neutrophils exposed to 2 μg/mL AZM while migrating through periodontal connective tissue toward the gingival crevice could accumulate an intracellular AZM concentration of ≈10 μg/mL. This is 20-fold higher than its MIC for A. actinomycetemcomitans strain Y4, at least five- to 40-fold higher than its MIC for most other strains of A. actinomycetemcomitans (0.25 to 2.0 μg/mL), and 10- to 80-fold higher than its MIC for most strains of Porphyromonas gingivalis (0.125 to 1.0 μg/mL).…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, in ventilator-associated pneumonia (VAP) patients with clarithromycin-resistant bacterial infections, combined treatment with clarithromycin was positively correlated with the time of resolution of the infection (4). Although it was proposed that some macrolides could induce degranulation and bacterial killing in polymorphonuclear neutrophils (PMNs), knowledge regarding their role in these cells has been very limited (5,6).…”
mentioning
confidence: 99%