Synergistic effects between amoxicillin, metronidazole, and the hydroxymetabolite of metronidazole against Actinobacillus actinomycetemcomitans

Pavičić, M. J. A. M. P.; Winkelhoff, A.J. van; Graaff, J. de

doi:10.1128/aac.35.5.961

Cited by 65 publications

(36 citation statements)

References 29 publications

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“…In part to validate the system, we compared the antimicrobial activities of different concentrations of amoxicillin (AMX), metronidazole (MTZ), and azithromycin (AZM), using chlorhexidine (CHX) as the gold standard and positive control. Using the system also allowed us to test the much-debated hypothesis (22)(23)(24) that MTZ and AMX act synergistically, rather than independently, in their antimicrobial activity against periodontal pathogens.…”

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confidence: 99%

Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on anIn VitroPolymicrobial Subgingival Biofilm Model

Soares

Teles

Starr

et al. 2015

Antimicrob Agents Chemother

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dChronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q ‫؍‬ 0.0207) but 54% more than AMX (q ‫؍‬ 0.0031), 72% more than MTZ (q ‫؍‬ 0.0031), and 67% more than AZM (q ‫؍‬ 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. P eriodontitis is a persistent health problem that affects the U.S. population in epidemic proportions. The most recent data from the National Health and Nutrition Examination Survey (NHANES) (2009 to 2010) suggest that the prevalence of chronic periodontitis among U.S. adults is over 47%, representing 64.7 million adults (1). Chronic periodontitis is the main cause of tooth loss in adults. Treatment costs U.S. taxpayers $4.4 billion each year (2), but existing therapies do not eradicate the disease. Frequent posttreatment follow-up visits are needed and are costly, which may be one reason why the prevalence is higher in populations of low socioeconomic status (3).A single periodontal pocket harbors a complex polymicrobial community of up to hundreds of taxa, and periodontal diseases are triggered by dysbiosis of subgingival organisms. Organization of the subgingival microbiota in biofilms makes it challenging to control periodontal infections, since biofilms help protect resident organisms from both antimicrobial agents and immune mechanisms (4). Still, the use of systemic and local antibiotics as an adjunct to mechanical treatment provides clinical benefit beyond that achieved by scaling and root planing alone (5-15).However, the threa...

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Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on anIn VitroPolymicrobial Subgingival Biofilm Model

Soares

Teles

Starr

et al. 2015

Antimicrob Agents Chemother

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“…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).…”

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confidence: 99%

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

Pajukanta

Asikainen

Saarela

et al. 1992

Antimicrob Agents Chemother

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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...

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“…One should first mechanically reduce the subgingival bacterial load, which might otherwise inhibit or degrade the antimicrobial agent. Disrupting the structured bacterial aggregates that can protect the bacteria from the agent the patient was prescribed medication which comprised of Amoxicillin (500 mg) TID and Metronidazole (400 mg) as the synergistic effect of metronidazole and amoxicillin on A. actinomycetemcomitans has been documented [4] with their efficacy and effectiveness proven in the treatment of GAgP as the tetracycline failure was seen in A.A suppression [5].…”

Section: Chartmentioning

confidence: 99%

Aggressive Periodontitis - A Comprehensive Treatment Approach

Bapure¹

2017

Austin J Dent

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Synergistic effects between amoxicillin, metronidazole, and the hydroxymetabolite of metronidazole against Actinobacillus actinomycetemcomitans

Cited by 65 publications

References 29 publications

Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on anIn VitroPolymicrobial Subgingival Biofilm Model

Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on anIn VitroPolymicrobial Subgingival Biofilm Model

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

Aggressive Periodontitis - A Comprehensive Treatment Approach

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