In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans

Abstract

The in vitro susceptibility of ActinobaciUlus actinomycetemcomitans to azithromycin, a new macrolide antibiotic of a new class known as azalides, was compared with that of erythromycin by the agar dilution method on Mueller-Hinton Haemophilus test medium. Eighty-two A. actinomycetemcomitans strains, 79 recent clinical isolates obtained from 40 periodontally healthy or diseased subjects, and 3 type strains were included in the study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans. Azithromycin, however, was highly effective against A. actinomycetemcomitans: all strains were inhibited at 2.0 ,ug/ml. Azithromycin exhibited the best in vitro activity against the serotype a subpopulation of A. actinomycetemcomitans: 1O0o of the strains were inhibited at 1.0 ,ug/ml. The lowest MICs were, however, recorded by serotype b strains. Since azithromycin has favorable pharmacokinetic properties, including excellent distribution into tissues, it could be expected to pass into gingival crevicular fluid at levels sufficient to inhibit A. actinomycetemcomitans in vivo. Therefore, it is a good candidate for future clinical trials in A. actinomycetemcomitans-associated periodontitis.Actinobacillus actinomycetemcomitans is a capnophilic gram-negative coccobacillus which has been associated with localized juvenile periodontitis and with some cases of refractory and rapidly progressing periodontitis (33). The distribution ofA. actinomycetemcomitans serotypes in periodontally healthy and diseased subjects has lately been reported by Asikainen et al. (3), who demonstrated that serotype b was dominant in the subjects with periodontal disease and that serotype c was the most common serotype in the healthy subjects. Patients with a positive finding forA. actinomycetemcomitans often fail to respond adequately to mechanical therapy only (21). Many antibiotics have been administered in the treatment ofA. actinomycetemcomitansassociated periodontal diseases. Despite the good in vitro susceptibility ofA. actinomycetemcomitans to tetracyclines (4,30), the clinical response has been variable (2, 27, 31). The favorable clinical results obtained with metronidazole are thought to be due to the better in vitro activity of the hydroxy metabolite of metronidazole against A. actinomycetemcomitans and the possible synergistic effects of these compounds in vivo (16). However, in some patients metronidazole alone may not be effective enough for the eradication of A. actinomycetemcomitans from the oral cavity (20,25). On the other hand, the production of 13-lactamase by other bacterial species in periodontal pockets may compromise the use of ,-lactamase-susceptible penicillins (32). Furthermore, the old macrolide antibiotic erythromycin penetrates insufficiently into gingival crevicular fluid (24). Thus, it is necessary to screen for alternative antimicrobial agents that would be active against A. actinomycetemcomitans to find potential candidates for therapeutical trials.During recent years, an extensive development has occurre...

Adjunctive azithromycin in the treatment of aggressive periodontitis: Microbiological findings of a 12-month randomized clinical trial

“…Sefton et al 15 demonstrated that subjects receiving azithromycin together with scaling and root planing presented significantly greater reductions in counts of spirochetes and black-pigmented bacteria in subgingival plaque than controls at 5 months posttherapy. In vitro studies have also demonstrated that azithromycin has a good inhibition effect on A. actinomycetemcomitans 13 and P. gingivalis. 12 In comparing these findings one should be cautious, given that these studies have investigated the clinical and microbiological effects of adjunctive azithromycin in the treatment of patients with chronic periodontitis.…”

“…10 Azithromycin is detected in high concentrations in periodontal tissues 11 and was found to be effective against periodontopathogenic bacteria in vitro. 12,13 It has been demonstrated that azithromycin improves periodontal health of chronic periodontitis (ChP) patients when used in combination with mechanical periodontal treatment. 14 Studies evaluating the effect of azithromycin on the periodontal microbiota of ChP showed inconsistent findings.…”

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

“…13,14 It is active against A. actinomycetemcomitans, and its therapeutic levels in gingival crevicular fluid are sustained for at least 14 days after the last oral dose. 15,16 Previous studies have shown that accumulation of AZM inside human gingival epithelial cells facilitates killing of intraepithelial A. actinomycetemcomitans . 13 When active transport of AZM was inhibited by a competitive inhibitor, there was a significant decrease in the killing of intraepithelial bacteria.…”

Biocompatibility of Azitromicyn on Connective Tissue

“…Microbiology research data states that mechanical treatment (scaling and root planing) alone was not able to completely eliminate bacterial pathogens, such as Actinobacillus actinomycetemcomitans from local and subgingiva, therefore antibiotic application was considered to be effective as an adjuvant. 6 Azithromycin is an effective antibiotic against gram-positive aerobic bacteria, gram negative, and strict anaerobes such as Bacteroides fragilis, Fusobacterium sp, Peptostreptococcus sp. In addition, azithromycin also showed good activity against Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis.…”

“…Its local usages are also expected to be more effective than erythromycin, and required a lower concentration than eritromisin. 6 In order to minimize the side effects of systemic-administered azithromycin and to make it more economical and affordable, the authors consider to prepare azythromycin as a local preparations. However its biocompatibility test needs to be carried out to determine the optimum concentration of therapeutical doses which will not harm the gingival and the surroundings tissues.…”