Chlorhexidine As An Antimicrobial Agent In Dentistry – A .

OHDM- Vol. 15- No.2 - April, 2016but also as an effective antimicrobial agent and its widerapplication in variety of oral disorders in variousformulations.leaving the other free to interact with bacteria attempting tocolonize the tooth surface. The process of bacterialsuppression therefore occurs at the tooth surface itself bychlorhexidine, there is no much supporting evidence for thisaction.Chlorhexidine as an Antiplaque AgentAlcohol is generally added to the most of antiseptic mouthwashes, it is important for stability of formulation and preventcross contamination. The accepted percentage of alcohol is11.6%.Some of the studies have shown that alcohol freechlorhexidine mouth rinses show significantly less side effect[27]. Some concerns were raised about association of alcoholwith oral cancer, whether these concerns are significantlyvalid has not been established. It is still an open questionwhether chlorhexidine should contain ethanol or not.Several invivo and invitro studies proved efficacy of 0.2%chlorhexidine as an antiplaque agent [9-16]. Effect ofchlorhexidine on plaque inhibition is dose dependant, the doseusually ranges in the concentration of 0.03 to 0.2% volume,frequency and concentration are important in determining theclinical response. The optimum dose of chlorhexidine as amouth rinse is generally considered to be 20 mg twice daily,similar levels of plaque inhibition can be achieved with largervolumes of lower concentrations. A lower concentration ofchlorhexidine has been tested in several studies and provedeffective. A persistent bacteriostatic action lasting for 12hours was observed. No significant difference in the plaquescores was observed when 0.2% of chlorhexidine mouthwashis used for 15,30,60 sec. There was no difference in plaqueinhibiting action of 0.1%, 0.12% and 0.2% of chlorhexidinerinses [17-22]. Adsorption of monolayer formed by lowconcentration CHX is more stable than the multilayered highconcentration over the microbial cell wall. Bonesvoll in hisstudy reported that there was rapid binding of chlorhexidine inthe mouth during the first 15 seconds of rinsing and nearly75% after 30 seconds of rinsing [14]. The effect ofchlorhexidine on mature plaque or biofilms is very lessbecause of the exopolymer matrix, bacterial enzymes and lowgrowth rate hinder the action of chlorhexidine [23]. Howeverthe recent invitro study has shown 0.12% chlorhexidine hadthe greatest antibacterial activity on both planktonic andbiofilm-grown organisms [24].Different formulations of chlorhexidine have beenformulated to replace alcohol. Cetyl pyridium chloride hasbeen used and studies are proved that it is as efficiant aschlorhexidine and alcohol combination and reduces theunpleasant side effect of mucosal irritation [28]. Alcohol freechlorhexidine preparations were found to be effective whencompared to placebo solution.Side Effects of Chlorhexidine- ResearchEvidenceThe most common side effect associated with the use ofchlorhexidine is brownish discoloration of teeth, restorationand tongue. Staining caused by chlorhexidine is not usuallyremoved by brushing with normal toothpaste, the exact reasonbehind the staining is still being debated [29-31]. Theproposed mechanisms are degradation of chlorhexidinemolecule to parachloraanaline, catalysis of mailard rections,protein denaturation with chromogens, metal sulphideformation, precipitation of anionic dietary compounds. Thereis no sufficient evidence to support the above threemechanisms. The more conclusive evidence to date is in favorof precipitation of dietary compounds onto adsorbedchlorhexidine molecule [31]. Studies have shown that if largervolumes are used lower concentration of chlorhexidine wasrequired. Staining is less with large volumes of diluteconcentration than with small volumes with higherconcentration. The higher percentage of chlorhexidine showsa stronger anti bacterial effect but with higher degree ofstaining. A new preparation which contains chlorhexidinewith additional anti -discoloration system not only promises toprevent plaque formation but also to avoid staining. Twoagents (sodium metabisulfate and ascorbic acid) are claimedto interfere with synergistic mechanism that causespigmentation without reducing antiplaque activity. Howevercontradictory findings are reported in few other studies statingthat compromised antiplaque efficacy with ADS system. 0.2%alcohol containing chlorhexidine preparations have shownsuperiority in plaque reduction and reducing bacterial vitalitycompared to solution with anti discoloration system [32-36].While efficient stain removal effect is ascertained there isneed to explore its antiplaque action by further studies.The substantivity of chlorhexidine is attributed to thecontrolled release system.The presence of β cyclo dextrinregulates and controls the amounts of CHX released. Greaterthe amount of β cyclo dextrin, the more progressive therelease of CHX. The development of a controlled releasesystem from cellulosic substrates can also be achieved usingmicrofibrillated cellulose (MFC). A new experimentalapproach was proposed for the development of a bio basedcontrolled release system. βCD and MFC were mixed togetherto create a synergy between both their abilities to control therelease of active molecules. The association of MFC and βCDafforded very promising results.The obtained release patternwas a combination of both the actions of MFC and βCD. MFCmainly acted on the burst effect, whereas βCD controlled andregulated the release of CHX over time. Thus, acomplementary action could be achieved by associating boththe release systems. Depending upon end-user requirements,the CHX/MFC/ βCD system would release higher amounts ofCHX progressively than the CHX/ βCD system [25].Some of the controversies exist with the mechanism ofaction of chlorhexidine. Over the years, it was accepted thatthe chlorhexidine is bound to the oral mucosal surfaces andgradually releases over a period of time [6,7]. However thismechanism is questioned by Jenkins et al 1988, suggestingthat the major action of chlorhexidine is due to release oftooth bound chlorhexidine rather than its oral retention or itsinitial bactericidal effects [26]. It is possible thatchlorhexidine molecule attaches to pellicle by one cat ion,There is some evidence that regular and frequentapplication of chlorhexidine mouth rinses may temporarilyimpair the taste sensation [29]. In a study of Lang NP, [37] itwas observed that short term impairment of salty taste with94

OHDM- Vol. 15- No.2 - April, 2016the use of 0.2% aqueous chlorhexidine solution. It washypothesized that chlorhexidine binds to specific sodiumreceptor molecule in the taste bud which is different thanreceptors for sweet, bitter and sour stimuli.of its degradation products P chloranaline. No evidence ofcarcinogenicity was found in rats after 2 years of up to 40mg/kg of chlorhexidine 0.6mg/kg/day p-chloraniline daily.Chlorhexidine as an Adjunct to Nonsurgical andSurgical Periodontal TherapyThere is some evidence that 0.2% chlorhexidine mouthwash has a role in calculus formation. But the evidence is notclear. Some of the studies have reported that chlorhexidinereduces calculus formation when used in 0.1% concentration.In the study of Loe et al 1971, it was observed that 0.2% ofchlorhexidine mouth wash temporarily inhibited the calculusformation [38]. In contrary to this some studies report thatchlorhexidine promotes supragingival calculus formation. In along term of study of two years it was observed that there wasincrease in the calculus index scores in the experimentalgroups compared to control group. The increased calculusscore didn’t correlate with increased gingival index scores. Itwas hypothesized that the increased calculus scores mayrepresents the incremental built up and hardening of the stainin the gingival third of the crown. Another possibility is thatthe increased calculus index is factual and in some wayconnected with effect of chlorhexidine either upon the salivaor the tooth pellicle. The exact nature of the deposit formedduring prolonged chlorhexidine experiments both from thepoint of view of its chemical composition and its attachmentto tooth surface as well, mechanism of its formation has to bestudied thoroughly.Chlorhexidine mouth rinsing is ineffective in eliminating amicrobiota located beneath the gingival margin, Subgingivalirrigation using chlorhexidine solution or even gels turn out tobe effective in the treatment of periodontititis presumably dueto its ability to retain biologically significant concentration ofchlorhexidine for sufficients length of time within theconfines of periodontal pocket [40-44]. Some of the studieshave reported the treatment of periodontal pocket withchlorhexidine irrigation as an adjunct to scaling and rootplanning, provides a significant improvement in probing depthand reduces the microbial load.43 The lowest optimalconcentration of chlorhexidine daily is 400ml of 0.02%chlorhexidine concentration. Substantivity was found to below [44].There was no clinical or statistical difference between 0.1and 0.2% chlorhexidine, when used as subgingival irrigant ina simplified oral regimen in the treatment chronic adultperiodontitis [44,45]. A multicentre study tested the efficacyof chlorhexidine chip when used as an adjunct to scaling androot planing in reducing the probing depth and attachmentlevel over a nine month period. Significant improvementsfrom baseline favoring chlorhexidine chip were observed forprobing depth and attachment level [46]. The use ofchlorhexidine chip containing 2.5 mg chlorhexidine in a crosslinked hydrolyzed gelatin matrix has reported to inhibit 99%of bacteria isolated from periodontal pocket [47]. Elick Sdetermined the efficacy against the microorganisms normallyfound in the oral cavity such as streptococci, enterobacteria,Candida albicans, Porphyromonas gingivalis, Aggregatibacteractinomycetemcomitans, and Fusobacterium nucleate andobserved significant inhibition of this organisms [48].With the prolonged use of chlorhexidine, desquamativelesions in the oral mucosa was observed in the small numberof individuals, this was perhaps due to precipations of acidicmucins and proteins that cover and protect mucousmembranes. This makes the mucous membrane vulnerable tomechanical trauma or to the cytotoxic effects of chlorhexidine[39].Effect of Chlorhexidine on Oral Microbial FloraSome of the studies support the view that the prolonged use ofchlorhexidine is not associated with the development ofresistant strains of microorganisms. Although the side effectof long term chlorhexidine use include tooth staining, noemergence of opportunistic pathogens or stable shift in theoral flora following extended use have been reported [1]. A 6month clinical study demonstrated that with the use of 0.2%chlorhexidine mouth wash, a reduction in the number of oralbacteria with no overgrowth by candida albicans or E. coli.The highly concenterated chlorhexidine varnish appeared tofulfill the criteria for adequate subgingival infection control.Varnish can be easily applied within the pocket using a bluntneedle, it seemed ideal as a vehicle for antiseptic deliverybecause crevicular fluid promotes its hardening, avoiding fastclearance from the subgingival area. Mechanical debridementwith subgingival chlorhexidine varnish application providesignificantly greater improvements in probing depth comparedto those obtained by scaling and root planing alone in thetreatment of chronic periodontitis [49]. Chlorhexidine alsofound to be more effective in treating oral malodour.The mostcompelling evidence was provided for CHX mouthwashes,and for those that contained a combination of CHX, Cetylpyridium chloride and zinc [50]. Use of chlorhexidine afterperiodontal surgery enhances wound healing [51]. Somecontrary studies have reported that intensive rinsing with highconcentration especially in surgeries in which bone is exposedresulting in delay and disturbed wound healing in humans.With the use of 0.1 and 0.2% wound healing was slightlydelayed. Chlorhexidine when used in the form of mouth washwas found to be interfering with granulation tissue formation[52].A number of studies have examined the ability to generateoral bacteria resistant to chlorhexidine in the laboratory. It wasreported that these resistant strains demonstrated an increasein MIC by total salivary flora and oral streptococci during thecourse of the study. However these alterations in MIC weretransient and not seen five months after the completion of thetrial, with no alteration of oral microflora. Collectively, theresults from a number of clinical studies have established thesafety and efficacy of chlorhexidine without development ofresistant organisms [1-3].CarcinogenicityCarcinogenicity studies have been performed in both rats andmice given oral chlorhexidine plus artificially increased levels95

OHDM- Vol. 15- No.2 - April, 2016Chlorhexidine and Its Use in HIV Infectionosteitis frequency [63]. Rodriquez further recommonded thatthe increase in concentartion from 0.2% gel to 1.2% may nothave much improved efficacy [64].Common oral disease such as gingivitis and periodontitis areusual in HIV patients. Palliative therapy for these conditionscan prevent the more serious complications. Chlorhexidineplays an important adjunctive role in the treatment of HIVassociated gingivitis and periodontitis. apthous stomatatis,candidiasis, herpes virus and HIV associated neoplasticlesions. Chlorhexidine found to be effective in reducingcandida species in HIV affected individuals and children[53,54].The study by Nelly altogether negated the effect ofchlorheidine gel in the management of alveolar osteitis [64].The variation in efficacy was attributed to age, underlyingdiagnosed pathology and obstructions to removal of impactedtooth, smoking habits etc. A Review by Daly B concluded thatmouthrinses (0.12% and 0.2% concentrations) both before andafter extraction prevented approximately 42% of drysocket.Compared to placebo, placing chlorhexidine gel (0.2%)after extractions prevented approximately 58% of drysocket.Rare cases of hypersensitity to chlorhexidine inpatients with allergies have been reported [65,66].In Patients with Drug Induced GingivalEnlargementChlorhexidine has an adjunctive role in the treatment of druginduced gingival enlargement [55]. The overall effect is notknown as the research is inadequate and consist of mixedreports. More research is needed to evaluate the effect ofchlorhexidine on the inflammation associated with gingivalenlargement.Chlorhexidine as a Denture DisinfectantWith the use of chlorhexidine mouthwash, the gingival healthwas found to be improved in patients with fixed prosthodontictherapy. Significant reduction in putative periodontalpathogens was observed in these patients. Application ofchlorhexidine gels for 2 weeks to fitting surface of maxillarydentures reduced inflammation and significantly reducedfungal activity [67]. Chlorhexidine solution can be used forshort term soaking of complete denture. Long term soaking ofdentures causes acrylic staining.Use of Chlorhexidine in Recurrent ApthousStomatitisChlorhexidine can be used in patients suffering from recurrentapthous ulceration on the basis that natural course of recurrentoral ulcers can be extended due to bacterial contamination.Several studies support the benefits of this therapy butchlorhexidine mouth rinse is of limited or no effect onestablished major apthous ulceration [56]. Studies have shownthat chlorhexidine mouth rinse can reduce the incidence,severity and duration of apthous ulceration whereaschlorhexidine gel significantly reduced severity and durationbut not incidence [57].Rinsing with 0.12% chlorhexidine for 14 days together withsoaking denture overnight the same solution eliminatedcandida albicans on the denture surface [68]. This indicatesthat has a considerable antifungal effect in the oral cavity andfurther, that fungi are the responsible micro-organism in ratherthan bacteria. frequently discolored the denture as well as ofrelapse after 14 days of treatment was observed. self-curedPMMA chair-side resin is a new dosage form for dentureinduced stomatitis. Conventional antifungal agent, althougheffective against planktonic cells, shows reduced activityagainst C. albicans biofilms in vitro. However, Chlorhexidineexhibited significant anti-biofilm activity in vitro, suggestingthat they are alternative therapeutic strategies for oralcandidiasis [70].Use of Chlorhexidine in Physically and MentallyHandicapped IndividualsDental care for the disabled person should include adjunctiveprocedure to supplement any impaired ability to controlplaque and gingivitis. Chlorhexidine 0.2% in the form ofspray are found to be equally effective when compared to0.2% mouth wash and also it requires a very less dose oneseventh of dose used as a mouth rinse [58,59]. This supportthe hypothesis that tooth bound chlorhexidine play animportant role than the other oral surfaces and questioned thereservoir effect of chlorhexidine.In patients with overdenture, application of chlorhexidinegel has shown significant reduction in bleeding score andpocket depths [71]. A combination of chlorhexidine andfluoride therapy has significantly reduced the caries incidenceon abutment tooth. In the surgical procedure of dental implantsplacement,chlorhexidine rinse was generally applied untilsuture removal in order to reduce the risk of infection and toaid healing [72].Chlorhexidine in the Treatment of Dry SocketPeri-implantitis is rapidly becoming a major oral disease. Inperi-implant biofilm,bacterial communities were identifiedbelonging to the genera Butyviribrio, rium,Peptococcus,Campylobacter and Treponema, whereas some of these were notobserved on dental biofilm [73,74]. (venecious pedraz)Chlorhexidine was found to be effective in the maintenance ofgingival health in patients with implants and significantreduction in bacterial level was observed with use tigenous additional effect in early healing wasA significant decrease in the incidence of dry socket wasobserved in the study of Larsen et al. [60] Hedstorm L 2007,found no effect on reducing alveolar osteitis [61]. Recently, abioadhesive gel form has become available and it is moreeffective than 0.2% mouth wash.Its main advantage is that itprolongs the bioavailability of chlorhexidine in the applicationarea. The topical application of bioadhesive chlorhexidine gelto the surgical wound during the postoperative week maydecrease the incidence of alveolar osteitis after extraction ofthe mandibular third molars [62]. Babar A reported that singleapplication of chlorhexidine gel effectively reduce alveolar96

OHDM- Vol. 15- No.2 - April, 2016observed for 0.12% CHX with hyalurinic acid mouthwashcompared to chlorhexidine mouth wash alone [75].chlorhexidine varnish have better effect compared to monthlyapplication. In the study of Shaecken et al. [89] the use of50% chlorhexidine varnish has shown suppression of S.mutans from the plaque samples of interproximal areas for aperiod of four weeks after single application. In another studyof the same author, [90] use of 40% chlorhexidine varnishwith two applications at two week intervals showed thesignificant effect on plaque S.mutans for a prolonged periodof five months. In a study of Qi Zang with 40% chlorhexidinevarnish significant reduction in plaque S. mutans counts in pitand fissures was observed for a period of six months [91].Dental caries being mutifactorial in nature and an array ofhost and envirnomental factors equally play an important rolein prevention. Despite of skeptism to what extent, reduction inS mutans might translate into a beneficial effect in theprevention of dental caries, chlorhexidine varnish can still beconsidered as potential caries preventive agentChlorhexidine as a Root Canal IrrigantIntracanal tissues treated with chlorhexidine completelyinhibited the growth of E. feacalis. The bovine dentine andpulp specimen took up and subsequently releasedchlorhexidine. Martin and Nind investigated the efficacy ofchlorhexidine as a presurgical disinfectant of apicectomy sitesand observed beneficial effects [77]. A number of studies haveproved that 2% chlorhexidine is found as effective as 5.25%sodium hypochlorite in reducing the growth of E.feacalis[78-85]. With the higher concentration the substantivity ofchlorhexidine was found to be for 12 weeks. It has beenstudied for its various properties such as antimicrobialactivity, residual antimicrobial activity, biocompatibility andan action on bacterial lipopolysaccharide [86]. Despite itsusefulness as an E. feacalis inhibitor chlorhexidine cannot beadvocated as main irrigant in standard endodontic casesbecause chlorhexidine do not dissolve necrotic tissueremnants, which decreases visiability and chlorhexidine is lesseffective on gram negative than gram positive bacteria. In thestudy of Dornellis-morgental it was observed that ofchlorhexidine irrigating solution may prevent activity but donot eradicate E. faecalis in the root canal system [78].A Meta analysis of clinical trials between 1975 to1994 oncaries inhibiting effect of chlorhexidine mouth wash, gel andtooth paste indicated an overall caries reduction of 46%. Amore recent research on anticaries effect of chlorhexidinecovering the period of 1995 to 2003 highlighted thatchlorhexidine varnish has moderate caries inhibiting effectwhen applied every three to four months but its cariesinhibiting effect seems to have diminished around two yearafter last application [87,94]. Chlorhexidine varnish alsofound to be effective in reducing root caries among high riskpopulation but there is no conclusive evidence [95]. Thoughthe concern was expressed about the high risk of bias andavailable data is insufficient to refute or support its use, withavailable little evidence it can be considered that thechlorhexidine varnish could be a potential caries preventiveagent [96,97]. Systemic review with meta-analysis of up todate clinical trials on the effect of chlorhexidine varnish oncaries may further give insight into more definitive role ofchlorhexidine varnish.Chlorhexidine and its Role in Dental CariesPreventionChlorhexidine found to be effective in reducing S. mutanscount in saliva and dental plaque. Many longitudinal studieshave proved that there is direct relation between the S. mutanslevel in plaque and saliva and incidence of caries. Theproposed mechanism of caries inhibition is, it can interferewith the metabolic activity of S. mutans by abolishing activityof phosphonyl pyruvate. Chlorhexidine in the form ofmouthwash and gel has found to be effective in reducing thelevel of microorganisms but faster recovery ofmicroorganisms to original level was a frequent observation[79]. Moreover, the use of these two preparations is associatedwith side effects like staining and altered taste sensation.However, with the use of chlorhexidine in the form of varnish,the level of microorganisms in saliva and dental plaque wassuppressed for extended period of time and it was found to beassociated with fewer side effects when compared to mouthwash and gel. Several studies have supported its ability tosuppress the S. mutans count in saliva and dental plaque andthereby reducing the incidence of dental caries [80-95].ConclusionChlorhexidine is not only an excellent antiplaque agent but italso possesses very good antimicrobial properties. Its broadantimicrobial spectrum can be considered as boon formaintaining overall oral health. A wealth of research supportsits use in various for

Chlorhexidine as an Antimicrobial Agent in Dentistry – A Review Parappa Sajjan1, Nagesh Laxminarayan2, Prem Prakash Kar3, Mangala sajjanar4 1Department of Public Health Dentistry, Mallareddy Institute of Dental Science, Hyderabad, India.2Department of Public Health Dentistry