The effect of subminimal inhibitory concentrations of antimicrobial agents on three bacterial mixtures

Abstract

A test tube technique was developed to screen bacterial mixtures to detect interbacterial interactions that play a role in determining sensitivity to antimicrobial agents. We found 3 mixtures where these bacterial interactions change the sensitivity to antimicrobials or change the proportions of each bacterial species in the mixture. The mixtures were: Fusobacterium nucleatum 102.3 and Bacteroides endodontalis ATCC 35406; F. nucleatum 102.3 and B. endodontalis BN11 a-f; and Capnocytophaga ochracea 1956c and Eubacterium saburreum 162.4. The antimicrobials used were metronidazole for the first 2 mixtures and tetracycline for the last. F. nucleatum seems to protect B. endodontalis from the action of metronidazole. Conversely, the growth inhibition of C. ochracea by E. saburreum was lifted when tetracycline was present. We also found that the growth of C. ochracea can then permit the subsequent growth of E. saburreum. The test tube method permits the evaluation both of interbacterial interactions and the detection of any protective mechanism against antimicrobial agents in a bacterial mixture. We found that F. nucleatum 102.3 can decrease the metronidazole level in the culture medium, and by the use of 14C-metronidazole we demonstrated that acetamide is produced from metronidazole.

Comparative clinical and microbiological effects of topical subgingival application of metronidazole 25% dental gel and scaling in the treatment of adult periodontitis

“…The reason for this delayed effect is not obvious. In vitro studies have suggested that the activity of "subminimal inhibitory concentrations" of metronidazole and other antibiotics against a mixed population of bacteria may be unpredictable due to metabolism of the drug by members of the flora (Lacroix & Mayrand 1989). However, it is less conceivable that such processes play a major role at the high concentrations obtained after topical application.…”

Effects of azithromycin versus metronidazole-amoxicillin combination as an adjunct to nonsurgical periodontal therapy of generalized aggressive periodontitis

“…[10,11] In addition to A. actinomycetemcomitans, this combination is active against Treponema denticola, Tannerella forsythia, Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia. [12][13][14] Azithromycin (AZT) is a macrolide antibiotic that has more potent activity against Gram-negative bacteria compared with erythromycin, can penetrate dental biofilms, and has good periodontal tissue penetration. [15][16][17][18] Higher concentrations persist in many tissues for 0-7 days using a simple dosage regimen.…”

Efficacy of Amoxicillin and Metronidazole Combination for the Management of Generalized Aggressive Periodontitis

“…In this combination, metronidazole, which metabolizes in liver where a highly effective hydroxymetabolite of the drug is produced, and amoxicillin synergistically act on A. actinomycetemcomitans , Treponema denticola , T. forsythia , and P. gingivalis 8,14,16,18‐20 . In addition to these species, Prevotella intermedia and Fusobacterium nucleatum have been shown to respond to metronidazole–amoxicillin combination 21,22 . Systemically administered amoxicillin and metronidazole and professional removal of supragingival plaque weekly for 3 months in patients diagnosed with refractory periodontitis results in stably low levels of periodontopathogens for 2 years 23 .…”

“…8,14,16,[18][19][20] In addition to these species, Prevotella intermedia and Fusobacterium nucleatum have been shown to respond to metronidazole-amoxicillin combination. 21,22 Systemically administered amoxicillin and metronidazole and professional removal of supragingival plaque weekly for 3 months in patients diagnosed with refractory periodontitis results in stably low levels of periodontopathogens for 2 years. 23 These reports provide encouraging evidence for the polypharmaceutical use of adjunctive antibiotics in periodontal treatment.…”