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Chlorhexidine: The gold standard antiplaque agent

December 2013
Journal of Pharmaceutical Sciences and Research 5(12):270-274

Authors:

Saveetha University

Chlorhexidine is one of the most widely and commonly used antiplaque and antigingivitis agent. The properties and mechanism of action of chlorhexidine must be understood in order to be put into maximum use. Chlorhexidine was used as a broad spectrum antiseptic since the 1950's. Its antibacterial action is due to the disruption of the bacterial cell membrane by the chlorhexidine molecules, increasing the permeability and resulting in cell lysis. It can be either bacteriostatic or bactericidal depending on the dose. It is available in different formulations. However it does have some side effects like permanent staining of teeth and dysgeusia. This article discusses the various clinical applications, properties and adverse effects of chlorhexidine.

Structure of chlorhexidine

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Chemical plaque control agents

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Chlorhexidine: The Gold Standard Antiplaque Agent

Shruti Balagopal1, Radhika Arjunkumar2

1Student,Saveetha Dental College, Chennai

2Senior Lecturer,Department of Periodontics

Saveetha Dental College, Chennai

Abstract

Chlorhexidine is one of the most widely and commonly used antiplaque and antigingivitis agent. The properties and mechanism of action of

chlorhexidine must be understood in order to be put into maximum use. Chlorhexidine was used as a broad spectrum antiseptic since the

1950’s. Its antibacterial action is due to the disruption of the bacterial cell membrane by the chlorhexidine molecules, increasing the

permeability and resulting in cell lysis. It can be either bacteriostatic or bactericidal depending on the dose. It is available in different

formulations. However it does have some side effects like permanent staining of teeth and dysgeusia. This article discusses the various

clinical applications, properties and adverse effects of chlorhexidine.

Keywords:

Chlorhexidine, mouthrinse, chemical plaque control

INTRODUCTION

Chlorhexidine is a gold standard against which other

antiplaque and antigingivitis agents are measured.

Understanding the properties and limitations of the molecule

can ensure that the efficacy of the agent is maximized and the

side effects are minimized allowing it to rightly remain the

gold standard.

Dental plaque

Dental plaque clinically is a structured resilient, grayish-

yellow substance that tenaciously adheres to the intraoral

hard surfaces including removable and fixed restorations [1].

Plaque control

It is the removal of microbial plaque and the prevention of its

accumulation on the tooth and adjacent gingival tissues to

prevent calculus formation. Plaque control can be of two

types

 Mechanical plaque control

 Chemical plaque control

Mechanical plaque control

Dental plaque is one of the most important etiological factors

in the onset of periodontal disease. Dental plaque mineralizes

to form dental calculus. Calculus formation is significantly

reduced by proper plaque control. Bacterial plaque can be

removed effectively by mechanical means. It is safe and

effective. The various methods include:

 Toothbrushes

 Interdental cleaning aids

 Dental floss

 Toothpick

 Interdental brush and swab

 Dentifrices

Chemical plaque control

Terminology

Antimicrobial agents: Chemicals that have a bacteriostatic or

bacteriocidal effect in vitro that alone cannot be extrapolated

to a proven efficacy in vivo against plaque.

Plaque reducing/inhibitory agents: Chemicals that have only

been shown to reduce the quantity and/or affect quality of

plaque which may or may not be sufficient to influence

gingivitis and/or caries.

Antiplaque agents: Chemicals that have an effect on plaque

sufficient to benefit gingivitis and/or caries.

Antigingivitis agents: Chemicals which reduce gingival

inflammation without necessarily influencing bacterial plaque

(includes anti-inflammatory agents).

Chemical plaque control agents [2]

The various chemical plaque control agents are listed in

Table 1.

Commercial mouthwashes can be classified into based on

their substantivity, range of antibacterial activity against

various plaque bacteria, possible anti inflammatory effect,

acceptable taste, ability to promote fresh mouth sensation.

They can also be classified as group A,B and C as follows,

 Group A agents- antiplaque

 Chlorhexidine, acidified sodium chlorate, salifluor and

delmopinol

 Group B agents-plaque inhibitory

 cetyl pyridinium chloride,

 essential oil and triclosan rinses

 used as adjuncts to mechanical cleaning

 Group C agents-Have a low to moderate activity and

are used for cosmetic purposes like breath freshening

 Sanguinarine , oxygenating agents, saturated pyrimidine,

hexetidine

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270

Table 1- Chemical plaque control agents

Bisbiguanide antiseptics

Bisbiguanide compounds are a group of chemical plaque

control agents and comprises of the following agents

 Chlorhexidine

 Alexidine

 Octenidine

From a therapeutic point of view, the most obvious benefit of

using mouth rinses is the potential to reduce plaque and

gingivitis and particularly in youngsters where mechanical

plaque control is not optimal in maintaining gingival health.

The ADA council for scientific affairs has proposed a

program for acceptance of plaque control agents. These

include that the patients be evaluated in placebo control trials

of 6 months or longer and demonstrate significantly improved

gingival health compared with controls [3].

To date the ADA has accepted 2 agents for treatment of

gingivitis which include prescription solution of

chlorhexidine digluconate oral rinse and non prescription

essential oil rinse.

CHLORHEXIDINE

History

Chlorhexidine was developed by Imperial Chemical

Industries in England during 1940’s.It was marketed as a

general antiseptic in the year 1950. In 1957 chlorhexidine

was introduced for human use in Britain as an antiseptic for

skin. Later it was widely used in medicine and surgery.

Plaque inhibition first investigated by Schroeder in 1969[4]. A

definitive study for caries inhibition by inhibition of dental

plaque was done by Loe and Schiott 1972[5].

Forms

Chlorhexidine is available in various forms such as

digluconate, acetate and hydrochloride salts which are

sparingly soluble in water.

Structure

Chlorhexidine is a symmetrical molecule.It has four

chlorophenyl rings and two biguanide groups connected by a

central hexamethylene bridge. (figure 1)

Figure 1- Structure of chlorhexidine

Characteristics

Chlorhexidine is an antimicrobial agent. It acts on the inner

cytoplasmic membrane hence it is a membrane active type of

substance. It is dicationic at pH levels above 3.5. It prevents

plaque accumulation, hence it is a antiplaque and

antigingivitis agent[6] and reduces the adherence of

Porphyromonas gingivalis to epithelial cells[7]. It can be

bacteriostatic or bactericidal depending on the dose. It acts

against a wide array of bacteria including Gram positive and

Gram negative bacteria, dermatophytes and lipolytic viruses.

It also acts against fungi, yeasts and some viruses including

Hepatitis B virus and Human Immunodeficiency Virus. It

acts against Streptococcus mutants making it anticariogenic

in nature. Studies have also shown that chlorhexidine has the

ability to neutralize pathogenic agents such as Streptococcus

aureus, Porphyromans gingivalis and Prevotella intermedia.[8]

Another most important unique property of chlorhexidine is

its substantivity. Substantivity refers to the oral retentiveness.

It depends upon various factors such as concentration, pH,

temperature and time of contact of the solution with oral

structures.[9]

Mechanism of action of chlorhexidine:

The mechanism of action of chlorhexidine is outlined in

table 2.

COMPOUNDS AGENTS

Enzymes Protease, Lipase, Nuclease, Dextranase, Mutanase, Glucoseoxidase, Amyloglucosidase

Bisbiguanides Chlorhexidine, Alexidene, Octenidine

Quaternary Ammonium

Compounds Cetyl pyridinium chloride, Benzalconium Chloride

Phenolic compounds Thymol, 4-Hexylresorcinol, 2-Phenylphenol Eucalyptol, Listerene

Fluorides Sodium fluoride, Sodium monofluorophosphate Stannous fluoride, Amine fluoride

Metal ions Copper, Zinc, Tin

Oxygenating agents Peroxides

Other Antiseptics Iodine, Povidone iodine, Chloramine-T Sodium hypochlorite, Hexetidine, Triclosan

Salifluor, Delmopinol

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271

Table 2- Mechanism of action of chlorhexidine

CHLORHEXIDINE FORMULATIONS

Mouthrinses

Chlorhexidine mouth rinses are available in the form of 0.2%

and 0.12%.There is equal efficacy for 0.2%and 0.12% rinses

when used at appropriate similar doses [10]. The time of

rinsing is 30 or 60 seconds depending on the adsorption rate

of antiseptics to the oral surfaces (50% of chlorhexidine binds

to receptors within 15 seconds) but this does vary from

individual to individual. The plaque inhibiting effect of a

0.2%chlorhexidine with rinsing times of 15, 30 and 60

seconds following a 72 hour non brushing period showed no

difference [11]. The ideal regimen is twice daily (morning and

night) which will have a substantivity for 12 hours.

The addition of fluoride to chlorhexidine is considered

questionable [12]. The concentration of 0.06% and sodium

fluoride 0.2% and 0.055% of stannous fluoride was

considered compatible with fluoride [13]. The chlorhexidine

monofluorophosphate complexes was considered

incompatible without fluorides [14].

Gel

The different available concentrations of chlorhexidine gel

are 1%, 0.2%, 0.12%. They are delivered in trays and

toothbrushes. Chlorhexidine gel, that is applied once a day

has therapeutic effects, like reducing oral malodour and

also reduces chlorhexidine staining [15].

Toothpastes

0.12% of chlorhexidine with 1 parts per million of fluoride

has antiplaque effects similar to chlorhexidine mouthwash.

However there were difficulties in incorporating

chlorhexidine into gels and toothpastes.1% chlorhexidine

used as slurries and rinsed twice per day for one minute

causes significant reduction in the plaque and gingival scores

but also causes stains. Chlorhexidine in dentifrices gained

little attention due to its possible interaction with anionic

ingredients contained in toothpaste and competition for oral

retention sites [16].

Sprays

0.1% and0.2% sprays have similar plaque inhibition

properties of 0.2% mouthwash. It is well received by

physically and mentally handicapped patients [17].

Varnishes

Chlorhexidine varnishes are used for prophylaxis against root

caries [18].

Sugar free chewing gum

Chlorhexidine remains unbound in this form. It contains

20mg of chlorhexidine diacetate. It is advised to chew 2

The bacterial cell wall is negatively charged and contains sulphates and phosphates

Dicationic positively charged chlorhexidine is attracted to the negatively charged bacterial cell wall with specific and strong

adsorption to phosphate containing compounds

Alters the integrity of the bacterial cell membrane and chlorhexidine is attracted to the inner cell membrane

Chlorhexidine binds to the phospholipids in the inner membrane and there is leakage of low molecular weight compounds

like potassium ions

By increasing the concentration of chlorhexidine there is progressive damage to the membrane

There is coagulation and precipitation of the cytoplasm by the formation of phosphate complexes which include adenosine

triphosphate and nucleic acids

Cytoplasm of the cells are chemically precipitated

Bactericidal stage which is irreversible

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272

pieces twice per day for 10 minutes. This procedure is said to

cause less stains. It is a good method of using chlorhexidine

for a long period of time [19].

CLINICAL APPLICATIONS OF CHLORHEXIDINE

It is used as an adjunct to oral hygiene and professional

prophylaxis. It is used post oral surgery in periodontal

surgery or root planing. Studies have shown that the daily use

of mouthrinse combined with toothbrushing resulted in

reduced interproximal plaque when compared with

toothbrushing and daily flossing [20]. Chlorhexidine is of

importance in the maintainance protocol in immediate

function implants as there is a correlation between plaque and

bleeding index revealed a good result for 0.2% chlorhexidine

gel for daily implant self care at 6 months [21]. It is used in

patients with intermaxillary fixation and in patients who are

under high risk of caries. For those patients who are

physically and mentally handicapped chlorhexidine sprays

can be used [22]. It is used in medically compromised patients

who are predisposed to oral candidiasis. Chlorhexidine is

used to limit the bacteremia and operatory contamination by

oral bacteria and as an adjunct to antibiotic prophylaxis.

Other uses of chlorhexidine include sub gingival irrigation,

management of denture stomatitis, hypersensitivity and for

oral malodour. Full mouth disinfection has been introduced

with scaling and root planing and the application of

chlorhexidine into periodontal pockets with daily use of

chlorhexidine rinses at home for 2 months [23]. Chlorhexidine

formulations have well proven short to medium term

application as adjuncts and even replacements for mechanical

cleaning but it is still controversial [24]. Wound healing is

enhanced when chlorhexidine rinses are used before

extractions and after scaling and root planing or periodontal

surgery [25]. Chlorhexidine is shown to induce changes to

human gingival fibroblast collagen production and non

collagen protein production [26]. There is 65% reduction in

collagen production and a 75% reduction in non collagen

protein production.

Halita is the name of a mouth rinse containing 0.05% of

chlorhexidine, 0.05% cetyl pyridinium chloride and 0.14% of

zinc lactate. It is used in the management of halitosis [27, 28].

Zinc is added as it has the ability to convert volatile sulfur

compounds and it also acts synergistically with

chlorhexidine. Other clinical benefits include its use as a root

canal irrigant [29] and in atraumatic restorative treatment

where chlorhexidine containing glass ionomer cement [30].

Chlorhexidine is also used for surgical skin preparation for

the patient and the surgeon. Chlorhexidine is used as a local

drug delivery system in the form of a bio-degradable chip to

be used in the subgingival environment [31]. There is

controlled delivery of chlorhexidine to the periodontal

pocket. A slow sub-gingival release of 2.5mg of

chlorhexidine is found to have an average drug concentration

greater than 125 microgram per milliliter for 7 to 10 days.

The concentration of the drug remains above the minimum

inhibitory concentration for more than 99% of the

subgingival micro-organisms from the periodontal pockets.

The results of several clinical trials have shown that the use

of the chlorhexidine chip in conjunction with scaling and root

planing is effective in reducing periodontitis, clinical

attachment loss and bleeding on probing over a period of 6 to

9 months. The use of the controlled release of chlorhexidine

delivery system during maintenance therapy allows greater

improvement in clinical signs of periodontitis. In subgingival

exudates, the serum proteins may effectively compete with

the bacteria for the chlorhexidine, thus reducing the

availability of the drug. This might account for the occasional

lack of clinical effectiveness when the agent is administered

subgingivally [32].

Toxicology and side effects [33]

The side effects of chlorhexidine include brown

discolouration of the teeth, restorative materials and dorsum

of tongue. There is taste perturbation. There can be oral

mucosal erosion which is an idiosyncratic reaction and is

dose dependent. The bitter taste is difficult to mask.

Chlorhexidine staining

There is degradation of the chlorhexidine molecule to release

parachloroaniline. Non enzymatic browning reactions take

place called catalysis of Maillard. Protein denaturation and

metal sulfide formation occurs and there is precipitation of

anionic dietry chromogens [34].

Metabolism of chlorhexidine

The chlorhexidine that is swallowed undergoes minimal

metabolic changes. It has a half life of 4 days and it is

excreted in faeces.

Safety of chlorhexidine

Chlorhexidine is poorly absorbed in the gut and displays very

low toxicity. It does not cause any teratogenic alterations.

There is no evidence of formation of carcinogenic substances.

Precautions

After the use of chlorhexidine mouthwash the intake of tea,

coffee and red wine must be avoided. The usage is restricted

in cases of anterior composite restorations and glass ionomer

restorations. There should be a 30 minute lapse between the

usage of a dentifrice and chlorhexidine mouth wash [35]. It is

so advised because the toothpastes contain detergents which

are predominantly anionic agents. Chlorhexidine molecule

being dicationic tends to bind with the anionic agents leading

to a reduction in the substantivity of chlorhexidine

mouthrinse.

Comparative studies

Increasing the rinsing frequency of cetyl pyridinium chloride

to four times a day has been suggested to produce efficacy

equivalent to that of chlorhexidine [8]. Listerine has a

moderate plaque inhibitory effect poor oral retention and

some antigingivitis effects [36]. Substantivity of hexitidine

is one to three hours and has some plaque inhibitory effects

[37]. The effect of three commercial mouth rinses on cultured

human gingival fibroblast, an in vitro study revealed that

chlorhexidine, listerine and povidone iodine are capable of

inducing a dose dependant reduction in cellular proliferation

of fibroblasts [38].

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273

CONCLUSIONS

Chronic periodontitis is always preceded by chronic

gingivitis; chemicals that inhibit plaque may be expected to

be of value in both the prevention and management of

periodontal disease in some individuals. Thus, the use of a

chemical plaque-inhibitory mouthwash as an adjunct to tooth

brushing may have a major effect on improving the oral

health of the individual. Chlorhexidine is one chemical

plaque control agent which has various clinical applications

in dentistry especially in Periodontics . Chlorhexidine in its

various formulations has come to stay and it is appropriate to

call it the gold standard chemical plaque control agent.

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Evaluation of the Effectiveness of a Mouthwash Containing Spilanthol and Cannabidiol on Improving Oral Health in Patients with Gingivitis—Clinical Trial

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Background/Objectives: Plaque-associated gingivitis is widely regarded as a local inflammatory condition initiated by the accumulation of a non-specific dental biofilm in the interaction with the host immune system. The initial symptom noticed by the patient is bleeding gums. The use of mouthwash can serve to supplement mechanotherapy. However, there is an increasing interest in mouthwashes comprising natural ingredients, including cannabidiol (CBD) and spilanthol. The objective of this study was to evaluate the effect of an oral rinse containing spilanthol and CBD oil compared to a rinse containing tea tree oil on the oral microbiota and the values of selected oral status indicators in patients with gingivitis. Methods: The study included 40 patients treated with a rinse containing tea tree oil (TTO)/TTO + spilanthol + CBD for a period of 42 days. Patients rinsed their mouth twice daily for 30 s. The patients’ oral microbiome was assessed before and after treatment, and bleeding on probing (BOP) and approximal plaque index (API) were assessed. The study was double-blind. Results: API and BOP were reduced in all groups, both the test and control. The most significant decrease in baseline BOP-1 scores was observed in test groups A and D (p = 0.005062 and p = 0.005062, respectively). A significant difference in API improvement was observed between the initial and final visits in the test (A, D) and control (B, C) groups (p = 0.012516, p = 0.005062, p = 0.004028, p = 0.003172, respectively). Conclusions: Firstly, the use of a mouthwash containing cannabidiol (CBD) and spilanthol was demonstrated to be efficacious in the maintenance of oral microbiota homeostasis. Secondly, the combination of TTO with spilanthol and CBD in the rinse was shown to result in a more significant reduction in selected oral health parameters (BOP and API) and anti-inflammatory effects when compared to a rinse with TTO alone. It should be noted that this is a pilot study and will continue.

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Chlorhexidine (CHX) remains the most effective antiseptic in periodontal therapy, multiple reports have identified ultrastructural antibacterial effects of CHX on oral bacteria, however, little is known about its molecular mechanism of action on Porphyromonas gingivalis, an important pathobiont directly associated with the pathogenesis of periodontitis. A standardized suspension of P. gingivalis ATCC 33277 was expose to 0.20% CHX for 1 min, then counting colony forming units (CFUs) were recovered to determine the percentage of microbial inhibition. Protein extract integrity of the bacterial cells exposed to CHX was evaluated on a one-dimension sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D SDS-PAGE) gel. The identification of the proteins expressed by P. gingivalis after its exposure to CHX was carried out by mass spectrometry (LC-MS). Exposure of P. gingivalis for 1 min to 0.20% CHX resulted in a 93% reduction in bacterial viability, in addition to an increase of 2.9-fold in protein expression, with the Lys gingipain protein showing the greatest increase. Exposure to 0.20% CHX 1 min on P. gingivalis resulted in 93% reduction in bacterial viability, in addition to inducing changes in the bacterial proteome, with an increased expression of gingipains, the main virulence factor of P. gingivalis.

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Full-text available

Nov 2024

Dental plaque provides a proper environment for the growth and activity of bacteria responsible for periodontal diseases and caries. As a result, it should be removed by individuals to prevent periodontal diseases and caries. There are different mechanical and chemical plaque control methods. In one study is shown that dental plaque removal efficacy of dentifrice containing Ethylenediaminetetraaceticacid(EDTA)/Methylsulfonylmethane(MSM) was nearly five times that of commercially available fluoride toothpaste. In another study, authors found that xylitol-containing chewing gums caused a marked reduction in the count of Streptococcus Mutans compared to conventional ones. This difference was highly prominent in individuals with poor oral hygiene. In this study we assessed the synergic effects of Xylitol, EDTA and MSM in a chewing gum in comparison with chlorhexidine mouthwash. This study was a crossover, randomized clinical trial. Twenty-four patients were divided in two groups randomly. At the baseline scaling and root planing was done for each patient. Group1 used chlorhexidine mouthwash twice a day. Group2 used novel chewing gum for 15 min twice a day. After 14 days, for every patient O’leary plaque index, gingival index and sulcus bleeding index were reevaluated and recorded. Professional brushing was done for patients. 14 days were considered as wash-out period. After that, method of plaque control of groups was changed. After 14 days, all patients were reevaluated and recorded and were compared with previous data. Samples in 2 groups had no significant difference in age and sex. Paired sample t test revealed that there were significant differences between first and second period for O’leary plaque index, gingival index and sulcus bleeding index in Group1 (P < 0.05). But in Group2 there were no differences between first and second period for all indexes. Also independent sample t test showed that there were no significant differences between baseline, after first treatment and after second one for all indexes in both groups (P > 0.05). According to regression model results, type of treatment had no effect on mean of all indexes. According to our findings which showed the similar efficiency of novel chewing gum and chlorhexidine mouthwash in improving and reducing plaque and gingival indexes, we can conclude that novel chewing gum can be introduced as an effective, cheap and accessible tool for dental plaque control. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-79551-4.

An Assessment of the Clinical Efficacy of a Topical Application of 5% Thymoquinone Gel for Plaque-Induced Gingivitis Patients: A Randomized Controlled Clinical Trial

Article

Full-text available

Sep 2024

Background: Gingival diseases, encompassing a spectrum of oral health concerns, represent a prevalent issue within the global population. Despite their widespread occurrence, the research landscape concerning effective interventions, particularly those rooted in herbal products, remains somewhat limited. Addressing this knowledge gap, the current study undertook a comprehensive evaluation aimed at assessing the clinical efficacy of a novel intervention: a 5% thymoquinone (TQ) gel. This investigation specifically focused on the application of TQ gel as an adjunctive measure to the standard protocol of scaling (SC) in individuals afflicted with plaque-induced gingivitis. Through rigorous examination and analysis, this study seeks to provide valuable insights into the potential utility and therapeutic benefits of this herbal-based intervention in managing gingival diseases. Objective: To evaluate the efficacy of 5% TQ gel using a novel liposome drug delivery as a topical application following SC in gingivitis patients. Methods: A double-blinded, parallel, randomized controlled clinical trial. The study was performed at the Faculty of Dentistry, King Abdulaziz University, and Qassim University, Saudi Arabia. This trial enrolled 63 participants in an age group between 18 and 40 years attending the outpatient clinics of the Faculty of Dentistry, Qassim University, Saudi Arabia, and a clinical diagnosis of gingivitis was made. The enrolled subjects were categorized into three groups: Group I—TQ gel with SC, Group II—Placebo with SC, and Group III—SC alone, and clinical outcomes were measured at baseline and two-week follow-up visits. Plaque index (PI), papillary bleeding index (PBI), and any adverse events with TQ gel are categorized as mild, moderate, and severe. 63 patients. Group I (n = 21); Group II (n = 21); Group III (n = 21). Results: The paired t-test compared the mean differences in PI and PBI at two time points and it was observed that there were significant differences in Group I with p-values of 0.04 and 0.05, respectively. A one-way ANOVA test was performed and it showed significant differences in the mean scores between the three groups for PI (p-value—0.01) and PBI (p-value—0.05). The post hoc Tukey’s test compared the mean differences in PI and PBI between the groups and the results were in favor of Group I which used TQ gel with SC. Conclusions: The clinical trial concluded that the plaque and gingival bleeding scores were significantly reduced in the group of patients who intervened with TQ gel following SC when compared to SC-alone and placebo groups. Also, there were significant reductions in the scores from the baseline to the two-week follow-up visit in patients treated with TQ gel and SC.

Molecular typing of reduced susceptibility of Acinetobacter calcoaceticus–baumannii complex to Chlorhexidine in Turkey by pulsed-field gel electrophoresis

Article

Aug 2024

Abdullah Tozluyurt

Introduction . The global spread of Acinetobacter spp., particularly the Acinetobacter calcoaceticusbaumannii (ACB) complex, has led to its recognition as a significant pathogen by the World Health Organization (WHO). The increasing resistance of the ACB complex to multiple antibiotics presents a challenge for treatment, necessitating accurate antibiotic susceptibility profiling after isolation. Hypothesis or gap statement . There is limited understanding of the antimicrobial resistance and chlorhexidine, a biocide, susceptibility profiles of ACB complex strains, especially in clinical settings in Turkey. Aim . This study aimed to identify ACB complex strains recovered from various clinical specimens at Hacettepe University Hospitals in Ankara, Turkey, in 2019, and to assess identification, their antibiotic and chlorhexidine susceptibility profiles, and genomic relatedness. Methodology . Eighty-two ACB complex strains were identified using MALDI-TOF MS. Susceptibility testing to 12 antibiotics was conducted using the disc diffusion method, and colistin, chlorhexidine susceptibility was assessed using the broth microdilution technique, following the latest EUCAST and CLSI guidelines. ACB complex members with reduced chlorhexidine sensitivity were further analyzed by pulsed-field gel electrophoresis (PFGE) for bacterial typing. Results . Among the isolates, 1.2% were multidrug-resistant (MDR), 73.2% were extensively drug-resistant (XDR), and 12.2% were pandrug-resistant (PDR). Carbapenem resistance was found in 86.7% of MDR, PDR, and XDR strains. Colistin resistance was observed in 15.8% of isolates, and 18.2% exhibited decreased susceptibility to chlorhexidine. PFGE revealed seven different clones among strains with reduced chlorhexidine sensitivity, indicating vertical transmission within the hospital. Conclusion . This study highlights the reduced susceptibility to chlorhexidine in ACB complex members and provides epidemiological insights into their spread. The findings underscore the importance of screening for antimicrobial resistance and biocide susceptibility profiles to effectively manage healthcare-associated infections.

In vitro evaluation of anti-microbial efficacy of Trigonella foenum-graecum and its constituents on oral biofilms

Article

Dec 2024

Background and Objective The extracts obtained from the leaves and seeds of Trigonella foenum-graecum (Fenugreek) are effective against various microbial infections. The phytoconstituents of Trigonella foenum-graecum have shown promising effects as anti-diabetics, anti-helmentic, anti-microbial, antifungal, and antipyretic, but its impact on oral pathogens is yet to be established. Therefore, the present study aimed to explore the antimicrobial efficacy of phytoconstituents of Trigonella foenum-graecum as compared to 0.2% chlorhexidine (CHX). Materials and Methods The methanolic extracts of Trigonella foenum-graecum i.e., fenugreek absolute (FA), diosgenin (DIO), and furanone (FU) were used in this study. The antimicrobial efficacy of these extracts was evaluated by testing the minimal inhibitory concentration, minimal bactericidal concentration (MBC), agar well-diffusion assay, colony-forming unit (CFU) count, and also by using confocal laser scanning microscopy (CLSM) against Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 35218, and Pseudomonas aeruginosa ATCC 27853. Results The results of the study demonstrated that Trigonella foenum-graecum has anti-microbial activity comparable to 0.2% CHX. Well-diffusion assay and CFU count assay of the extracts showed statistically significant ( P < 0.001) results. MIC and MBC values were observed for FA, DIO, and FU compared to CHX against these selected test organisms. These results were confirmed by visual validation with CLSM. Conclusion The use of herbal alternatives in periodontics might prove to be advantageous. Trigonella foenum-graecum can be used as a promising alternative to CHX against S. aureus, E. faecalis, E. coli , and P. aeruginosa for the management of oral and periodontal infections.

Assessing the Efficacy of Chlorhexidine in Combating Most Important Causative Agents of Fungal Keratitis: An in Vitro Comparative Study With Seven Antifungal Agents

Article

Oct 2024
CURR EYE RES

Purpose: Fungal keratitis (FK) is a difficult condition to treat, particularly in underdeveloped nations. The study aimed to compare the in vitro activity of chlorhexidine (CHX) and seven antifungal agents against a collection of fungi recovered from FK patients. Methods: Seventy-three fungi were collected from patients with FK included in study. The antifungal agents tested were fluconazole, voriconazole, posaconazole, miconazole, natamycin, amphotericin B, and caspofungin. The concentration range for CHX was 1-1024 μg/mL. Assessments of antifungal susceptibility were conducted using the EUCAST broth microdilution reference method. Results: The findings demonstrated the beneficial in vitro inhibition of filamentous and yeast fungi by CHX. CHX demonstrated efficacy against Fusarium spp., Aspergillus spp., Candida spp., S. apiospermum and dematiceous fungi at concentrations of 4-64, 32-64, 4-32, 8, and 4-16 µg/mL respectively. The median MICs and MIC distributions of CHX showed no significant differences among the evaluated spp. (p > 0.05). The most effective antifungal drug was posaconazole, which was followed by voriconazole, caspofungin, and amphotericin B. Conclusion: In situations where access to a range of antifungal medications and microbiological facilities is limited, CHX should be further investigated as a potential treatment for FK. It might be able to treat the condition as an inexpensive topical treatment.

Review - Expert Opinion on Antibiotics and Antibiotic Resistance in Dermatology

Article

Full-text available

Oct 2024

Introduction: Antibiotic resistance has become a serious, severe problem worldwide. This issue does not only relate to the use of systemic antibiotics but to topical ones as well, like systemic therapies and local treatment of skin and mucosal infections. Antiseptics, an alternative to the topical treatment with antibiotics of wounds and some inflammatory dermatological conditions, tend to be microbicidal and have a broader spectrum of antimicrobial activity than antibiotics. Among these, polyhexanide (PHMB) allows for the control of the infection while avoiding the development of resistance. Objectives: Recommendations on the rules of good clinical practice for the management of small wounds, burns and post-traumatic ulcerative wounds, impetigo or folliculitis in the initial stages, and acne. Methods: Literature review on the principal topical therapies for small wounds, injuries, impetigo, folliculitis, and acne and a proposal of innovative, highly-tolerated treatments. Results and conclusions: Given the abuse of topical antibiotics in dermatology, for the treatment of small wounds, injuries, localized folliculitis, impetigo, and acne, the use of alternative topical treatments like polyhexanide and Rigenase® is recommended.

Evaluating the Effectiveness of Amarantha and Chlorhexidine Mouthwashes in Chronic Generalized Gingivitis: A Randomized Clinical Trial

Article

Sep 2024

A BSTRACT Aim The current study’s objective was to assess and contrast the benefits of herbal and chemical mouthwash in patients with persistent, widespread gingivitis. Material and Method Forty-five patients between the ages of 30 and 50 having persistent generalized gingivitis were enrolled in the study and randomly assigned to three groups: Group A received oral prophylaxis, group B received oral prophylaxis and prescribed chemical mouthwash, group C received oral prophylaxis and prescribed herbal mouthwash. The patients were under observation for forty-five days. At the baseline, 7 th , 30 th , and 45 th day gingival index was measured, and the data were statistically analyzed. The one-way ANOVA and Tukey’s post-hoc test were performed. Result The gingival index showed a significant difference. Over time, the gingival index tends to decrease with the use of herbal mouthwash. Conclusion In summary, our initial investigation demonstrates that herbal mouthwashes are just as successful in reducing gingival inflammation as chlorhexidine further significant difference observed in 30 th and 45 th day with chlorhexidine. Therefore, in addition to routine dental care, these ayurvedic medications can be taken to reduce gingivitis.

Synthesis and toxicity evaluation of a spray consisting of silver nanoparticles, ethylenediaminetetraacetic acid, methylsulfonylmethane, and xylitol on vero cell line

Article

Full-text available

Aug 2024

Introduction Dental plaque is a biofilm or an accumulation of bacteria that grows in the internal surfaces of the mouth and can be observed as a white to pale yellow layer over or between teeth. The continuous formation and accumulation of dental plaque lead to oral diseases. As a result, it is necessary to prevent the aggregation of dental plaque and clean it daily. Recently, ethylenediaminetetraacetic acid (EDTA) has been utilized in toothpaste to prevent plaque formation as an EDTA-transporting enhancer, methylsulfonylmethane (MSM) can effectively increase its local effect. Xylitol decreases the Streptococcus mutans count by changing the metabolic pathways. Aims In the present study, we synthesized a solution containing silver nanoparticles, EDTA, MSM, and xylitol and evaluated its toxicity on the Vero cell line through the MTT assay. Materials and Methods To produce silver nanoparticles, we dissolved silver nitrate in sodium citrate. Then we used a solution of distilled water and polyvinylpyrrolidone, which resulted in the encapsulation and stabilization of silver nanoparticles, and the solution was made by mixing other ingredients. We evaluated the cytotoxicity of this spray using the Vero cell line. We cultured the cells in the 10% FBS-containing RPMI culture medium. For performing the cytotoxicity test, we put 10,000 cells in each well of the 96-well plate, and the next day added the synthesized solution to each well at dilutions 0.05%, 0.1%, 0.2%, 0.5%, 1%, 2%, 5%, and 10%. As the control group, we used 4 wells containing live Vero cells without adding the solution. After 24, 48, and 72 h, we added the MTT solution to each well and incubated the plates at 37°C for 4 h. Finally, we evaluated the rate of living cells by reading the absorbance with an ELISA device at 570 nm. Results and Discussion We used the Mann–Whitney nonparametric test to evaluate the cytotoxicity of different concentrations of the synthesized spray solution and compare the cell viability rate of groups with the controls in various periods. According to the cytotoxicity results of different concentrations of the spray solution on the Vero cell line, there was no significant difference in cytotoxicity between the 0.05%, 0.1%, 0.2%, and 0.5%, and control groups at 24, 48, and 72 h ( P > 0.05). No significant difference existed in cytotoxicity between 1% and 2% concentrations and the controls 24 h after exposure; this became significant after 48 and 72 h ( P = 0.014). However, a significant difference existed in cytotoxicity between 5% concentration and the controls 24, 48, and 72 h after exposure ( P = 0.014). The CC 50 of the spray solution was calculated at 3.51%. Conclusion The findings of this study showed that the synthesized solution is nontoxic; therefore, this spray solution can be used safely as an oral mouthwash and spray.

Effect of three commercial mouth rinses on cultured human gingival fibroblast: An in vitro study

Article

Full-text available

Jan 2008
Indian J Dent Res

Aim: To examine the effect of three commercial mouth rinses (Hexidine 0.2%, Listerine Cool Mint, Betadine 1%) upon cultured human gingival fibroblast proliferation. Materials and Methods: Human gingival fibroblasts were cultured and incubated in Dulbecco′s Minimum Eagle′s Medium containing Chlorhexidine, Listerine, Povidone-Iodine at varying concentrations (1%, 2%, 5%, 10%, 20% and 100% of the given solution) at 37°C for 1, 5 and 15 min. Control cells received an equal volume of Dulbecco′s Minimum Eagle′s Medium without adding mouth rinses, for similar duration of exposure at 37°C. Following incubation the media were removed, cells were washed twice with medium, supplemented with 10% Fetal Bovine Serum, and fibroblasts in the test and control group were allowed to recover in the same media for 24 h. Results: In all the three groups, the proliferation inhibition was dependent on the concentration of solublized mouth rinses in the cell culture but independent of the duration of exposure to all three mouth rinses. The results showed that all three solutions were toxic to cultured human gingival fibroblasts, Chlorhexidine being the most cytotoxic. It was seen that at dilute concentrations (1% and 2% of given solutions) Listerine was more cytotoxic than Chlorhexidine and Povidone-Iodine. Conclusion: These results suggest that Chlorhexidine, Listerine and Povidone-Iodine are capable of inducing a dose-dependent reduction in cellular proliferation of fibroblasts. The results presented are interesting, but to know the clinical significance, further studies are needed.

Nonfluoride caries-preventive agents Executive summary of evidence-based clinical recommendations

Article

Sep 2011
J AM DENT ASSOC

Background. In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries-preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries. Types of Studies Reviewed. A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of nonfluoride caries-preventive agents. Results. The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents. Clinical Implications. The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences. (The full report can be accessed at "http://ebd.ada.org/ClinicalRecommendations.aspx".)

Combination of chlorhexidine and fluoride in caries prevention. An animal experiment

Article

Jan 1974

The effects on dental plaque, caries, molar surface dissolution rate and fluoride content of daily topical applications of 0.016 M solutions of chlorhexidine acetate (ChlAc), chlorhexidine hydrofluoride (ChlHF), chlorhexidine hydrochloride (ChlHCl) and of sodium fluoride (NaF) were tested in factorial arrangement in a short term rat caries test performed on 6 groups of 12 Osborne Mendel rats fed the high sucrose diet 2000a during a 20 day experimental period. Plaque formation was strongly inhibited by the readily soluble chlorhexidine compounds but not by NaF. Fluoride did not affect the plaque inhibiting properties of chlorhexidine. Smooth surface caries was strongly depressed by ChlAc, ChlHF and NaF but not by ChlHCl. Fissure caries was inhibited by both NaF and ChlAc and their effects were additive. While ChlHCl was ineffective, ChlHF was highly cariostatic. Molar surface dissolution rate and fluoride uptake were significantly influenced by chlorhexidine.

Clinical Periodontology and Implant Dentistry

Article

Jan 1997

Formation and Inhibition of Dental Calculus

Article

Nov 1969

Inhibition of experimental caries by plaque prevention. The effect of Chlorhexidine mouthrinses

Article

Feb 1972
EUR J ORAL SCI

abstract – The purpose of this study was to test the hypothesis that a frequent intake of sucrose does not produce caries if the teeth are regularly treated with an antibacterial agent. Twenty-four students with clean teeth and normal gingivae were assigned to one of the following three groups: (1) eight individuals ceased all active oral hygiene measures and rinsed 9 times daily with 50% sucrose, (2) eight students refrained from all active oral hygiene procedures, rinsed 9 times daily with sucrose and twice daily with 10 ml 0.2% chlorhexidine gluconate, (3) the third group consisted of two subgroups each comprising 4 students. One subgroup ceased all oral hygiene procedures and rinsed twice daily with 0.2% chlorhexidine gluconate. The other was instructed to practice meticulous tooth brushing twice daily. The experiment lasted for 22 days. The group who rinsed with sucrose showed heavy plaque accumulation, those who rinsed with sucrose + chlorhexidine showed a drastic reduction in the formation of plaque. In the subgroup rinsing with chlorhexidine only and in that performing good oral hygiene, plaque was non-existent. The gingival state essentially paralleled the plaque formation. The sucrose group showed a definite increase in Caries Index. No significant changes occurred in the group rinsing with sucrose + chlorhexidine, with chlorhexidine only, or in the group performing good oral hygiene. It is concluded that prevention of plaque formation inhibits the development of gingivitis and dental caries, even with frequent rinses of sucrose.

Evaluation of the Perioperative Use of 0.2% Chlorhexidine Gluconate for the Prevention of Alveolar Osteitis After the Extraction of Impacted Mandibular Third Molars: A Clinical Study

Article

Jun 2011

To clinically evaluate the perioperative use of 0.2% chlorhexidine gluconate for the prevention of alveolar osteitis, to assess the patient compliance to chlorhexidine and to prepare a comprehensive treatment plan to prevent alveolar osteitis after removal of an impacted third molar extraction. A prospective study was done on 50 patients with bilaterally impacted lower third molars which were indicated for extraction. Extraction of impacted mandibular third molar on one side was done without using any mouthrinse. While extracting the third molar on the other side, patients were instructed to use chlorhexidine 0.2% mouth rinse for 8 days, 1 day preceding and 7 days following the surgery. They were instructed to use chlorhexidine 0.2% (Rexidine) mouth rinse for 30 s twice a day (before breakfast and after dinner) with 15 ml of the rinse with 1:1 dilution with clean water. All the patients were evaluated for pain, presence or absence of clot and condition of the alveolar bone for the diagnosis of dry socket. Incidence of dry sockets was 8%, when patients did not use 0.2% chlorhexidine gluconate perioperatively which is statistically significant. It appeared that the incidence of dry socket can be reduced significantly by using 0.2% chlorhexidne gluconate mouth rinse perioperatively (twice daily, 1 day before and 7 days after surgical extraction.

Nonfluoride caries-preventive agents

Article

Sep 2011

In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA)Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries. A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of non fluoride caries-preventive agents. The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents. The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence based approach to care, these clinical recommendations should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.

A Comparison Between Chlorhexidine and some Quaternary Ammonium Compounds with Regard to Retention Salivary Concentration and Plaque-Inhibiting Effect in the Human Mouth after Mouthrinses

Article

Feb 1978
ARCH ORAL BIOL

The oral retention of chlorhexidine, cetylpyridinium chloride and hexadecyltrimethylammonium bromide (a component of cetrimide) was measured by means of 14C-labelled compounds in 7 subjects after 10-ml 2.2 mM mouth rinses for 1 min. The oral retention of chlorhexidine was 32 ± 6 per cent, of cetylpyridinium chloride 65 ± 5 per cent and of hexadecyltrimethylammonium bromide 70 ± 7 per cent of the administered dose. The salivary concentration was measured after similar mouth rinses in 3 subjects and calculated according to the 14C-activity of saliva samples from 0.5 to 24 h after the rinsing. Although the concentrations of the quaternary ammonium compounds were usually higher than those of chlorhexidine shortly after rinsing, their concentrations were significantly lower (p < 0.001) than those of chlorhexidine from 4 h and onwards. The plaque-inhibiting effect was assessed in subjects who rinsed with 2.2 mM test solutions twice daily for 3 days, using sucrose rinses to provoke plaque formation. The plaque-inhibiting effect of the quaternary ammonium compounds was also tested when used in a mouth rinse four times daily. A moderate degree of plaque inhibition was obtained when the quaternary ammonium compounds were used twice daily. When the frequency was increased to four times daily, the plaque-inhibiting effect of the quaternary ammonium compounds seemed to approach that of chlorhexidine.

Prevalence and Risk Indicators for Periodontal Attachment Loss in a Population of Older Community-Dwelling Blacks and Whites

Article

Sep 1990

The extent and severity of periodontal attachment loss are described for a random sample of 690 dentate community-dwelling adults, aged 65 or over, residing in five counties in North Carolina. In addition, risk indicators for serious levels of loss of attachment and pocket depth in this population are presented. Pocket depths and recession were measured on all teeth by trained examines during household visits. Blacks had an average of 78% of their sites with attachment loss and the average level of loss in those sites was approximately 4 mm, as compared to 65% and 3.1 min for whites. Because the extent and severity scores in this population were much higher than in younger groups, a serious condition in this group was defined as having 4+ sites of loss of attachment of 5+ mm with one or more of those sites having a pocket of 4+ mm. Bivariate analyses identified a large number of explanatory variables that were associated with increased likelihood of having the more serious periodontal condition. The logistic regression model for blacks includes the following important explanatory variables and associated odds ratios: use to tobacco (2.9), colony counts of B. gingivalis greater than 2% (2.4) and B. intermedius greater than 2% (1.9), last visit to the dentist greater than 3 years (2.3), and gums bleeding in the last 2 weeks (3.9). The model for whites indicated that tobacco use (6.2), presence of B. gingivalis (2.4) and the combined variable of having not been to the dentist in the last 3 years and having a high BANA score (16.8) were important explanatory variables.(ABSTRACT TRUNCATED AT 250 WORDS)