Structural Determinants of Activity of Chlorhexidine and Alkyl Bisbiguanides Against the Human Oral Flora

Abstract

We assayed chlorhexidine and a series of its analogues, in which the chlorophenyl terminal substituents were replaced with alkyl chains, for their in vitro antimicrobial activity against the Gram-negative and Gram-positive oral bacteria. Changes in antimicrobial activity were correlated with changes in agent structure for identification of structural criteria which may be important in the optimization of agent activity. Chlorhexidine showed substantial antimicrobial activity against the Gram-negative as well as the Gram-positive oral bacteria. The alkyl agents were comparable with chlorhexidine in their activity against Bacteroides gingivalis and Bacteroides intermedius, black-pigmented Gram-negative obligate anaerobes associated with periodontal disease in adults. Alkyl agents alexidine, heptihexidine (1,6-bis-n-heptylbiguanidohexane), hexoctidine (1,8-bis-n-hexylbiguanidoctane), and hexhexidine (1,6-bis-n-hexylbiguanidohexane), as well as chlorhexidine, were active against Actinobacillus actinomycetemcomitans, a Gram-negative organism associated with localized juvenile periodontitis. Hexidecidine (1,10-bis-n-hexylbiguanidodecane) and heptoctidine (1,8-bis-n-heptylbiguanidooctane) were more active, and hexhexidine was as active as chlorhexidine against Fusobacterium nucleatum, also associated with periodontal disease. Seven of the agents were more active than chlorhexidine against Actinomyces species. All test agents were active against Streptococcus mutans, a Gram-positive coccus associated with dental caries. Hexidecidine had activity equal to that of chlorhexidine when evaluated against the entire battery of organisms. Analysis of structure-activity relationships revealed that alkyl chains could replace chlorophenyl groups with retention or improvement of antimicrobial activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The in vitro effects of chlorhexidine on subgingival plaque bacteria

“…The antimicrobial effectiveness of chiorhexidine is known to be antagonised by blood and serum. MIC values obtained in the present investigation show some agreement with those reported by Baker et al (1987) in the case of organisms such as Capnocytophaga spp., Veillonelta parvula, Haemophilus aphrophilus and Streptococcus mutatis, especially when the range of MIC values is considered. The most extensive investigation into the sensitivity of oral streptococci to chiorhexidine is that of Riadom Schiott & Loe (1972), who found that its MIC for 280 strains ranged from 0.5 to 32 //g/ml.…”

“…Caiman & Murray (1956) reported a four to twelve-fold reduction in its activity in the presence of blood. This may be due to the greater proportion of blood used in the assay medium (10% in this study as opposed to 5% in that of Baker et al (1987)) and the larger inoculum used in this study (10" cfu/ml as opposed to 10' cfu/ml). These values, however, were obtained using a medium which did not contain blood, and so they cannot be compared with the results obtained in the present study.…”

“…Such agreement may be attributable partly to the fact that in both of these studies blood was incorporated into the assay media whereas it was omitted from the medium used by Hennessey (1973). Data concerning the effect of chiorhexidine on organisms found in subgingival plaque are also very sparse-the only study of this type published to date being that of Baker et al (1987). Caiman & Murray (1956) reported a four to twelve-fold reduction in its activity in the presence of blood.…”

Interaction of Chlorhexidine with Cytoplasmic Membranes of Streptococcus mutans GS-5

“…1). Our findings, together with previous results [Baker et al, 1987], lead us to speculate that the mode of action of CHX is mainly attributed to its hydrophilic property. CHX, being cationic, possibly adsorbs to bacterial surface by interaction with negative-charge membrane components.…”

Antimicrobial effect of alexidine and chlorhexidine against Enterococcus faecalis infection

“…23 ALX, similar to CHX, is a cationic bisguanide that induces lipid phase separation and domain formation at bacterial membranes. 24 However, ALX has greater affinity for bacterial LTA than CHX. 19 This characteristic might result in the formation of many ruptured (damaged) or antiseptic-attached bacteria in the 10-min-soaked ALX group.…”