Antiseptics Prescription for the Prevention and Treatment of Periodontal Diseases: A Comprehensive Review
ABSTRACT
Background and Aims
Antiseptics have been widely used in periodontology and implantology as an adjunct to mechanical plaque control. The main objective of this review was to summarize the best evidence for the use of antiseptics in the prevention and treatment of periodontal and peri-implant diseases.
Methods
A comprehensive literature search was conducted across multiple databases, including Scopus, PubMed/Medline, Web of Science, and ScienceDirect. Keywords such as (Antiseptics OR mouthwashes) AND (gingivitis OR periodontitis OR peri-implantitis OR mucositis) were used. Inclusion criteria included narrative or systematic reviews with or without meta-analysis and clinical studies. In vitro, animal studies, and case reports were excluded.
Results
Antiseptics, including chlorhexidine, essential oils, and povidone-iodine, proved effective in reducing gingival inflammation and improving the plaque index. Other molecules, such as octenidine dihydrochloride, showed some effectiveness, although further studies are needed to expand their use.
Conclusion
Antiseptics play a crucial role in improving periodontal health. Prescriptions should be tailored to therapeutic goals to ensure appropriate dosage and duration, while avoiding excessive use.
1 Introduction
Periodontal diseases such as gingivitis and periodontitis are multifactorial, chronic inflammatory diseases associated with dysbiotic dental biofilms. Periodontal treatment initially includes improving individual mechanical plaque control and supra and subgingival instrumentation [1]. Antiseptics have also been recommended as an adjunct to mechanical plaque control [2, 3].
Antiseptics are external-use antimicrobial products (for skin and mucous membranes) with fairly rapid but transient and nonspecific action, generally exerting direct toxicity on the cell wall of microorganisms. Thus, causing either a bacteriostatic action, displacing Ca2+ and Mg2+ ions and causing the loss of K+ from the cell wall, or a bactericidal action, by causing the leakage of all major intracellular components [4]. The antiplaque activity can be achieved through various mechanisms of action by preventing bacterial adhesion; limiting bacterial growth and/or coaggregation; by disrupting an already established biofilm; modifying the composition and/or pathogenicity of the biofilm; reducing the number of bacteria present in the biofilm [5].
Antiseptics have been widely used in periodontology and implantology as an adjunct to mechanical plaque control. Many different antiseptic molecules have been studied and compared for their effect on plaque and inflammation parameters. Nowadays, many pharmaceutical formulations and clinical indications are available, providing a wide range of options for periodontists when prescribing, mainly topical supragingival application. The local (subgingival) administration of antiseptics, such as extended-release CHX in patients with periodontitis, offers limited benefit as a professional application [2, 6].
The present review highlights the different antiseptic molecules, their indications in the treatment of periodontal and peri-implant diseases, and the timing and modalities of prescription. The main objective was to summarize the best evidence for supra-gingival use of antiseptics use in the prevention and treatment of periodontal and peri-implant diseases.
2 Methods
We selected and summarized published information that is relevant to the use of antiseptics in the prevention and treatment of periodontal and peri-implant diseases.
A comprehensive literature search was conducted across multiple databases, including Scopus, PubMed, Web of Science, and ScienceDirect. The search strategy employed a combination of relevant keywords: (Antiseptics OR mouthwashes OR Chlorhexidine OR Cetylpyridinium chloride OR Essential oils OR Triclosan OR Povidone-iodine OR Delmopinol OR “Natural products” OR Hexetidine OR Alexidine OR “Oxygenating Agents” OR Octenidine OR fluoride OR “Zinc salts” OR Detergents) AND (gingivitis OR gingiv* OR periodontitis OR periodont* OR “necrotizing periodontal diseases” OR periodontics OR mucositis OR peri-implant mucositis OR peri-implantitis OR implant OR orthodontic).
The inclusion criteria were interventional clinical studies, such as randomized controlled trials (RCT), controlled clinical trials, and observational studies. Additionally, systematic reviews, meta-analyses, narrative reviews, and book chapters addressing the use of antiseptics in periodontology and implantology were included. No restrictions were applied regarding language or year of publication. In vitro studies, animal studies and case reports were excluded. Studies about subgingival irrigation and locally administered antiseptics were also excluded.
3 Results
3.1 The Antiseptic Molecules
3.1.1 Chlorhexidine
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Antibacterial effect: Related to the modification of cell membrane permeability [8]. At low concentrations (0.02%–0.06%), CHX causes a bacteriostatic effect. At high concentrations ( > 0.1%), CHX causes a bactericidal effect (cell lysis and death).
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Antiviral Effect: Also due to the modification of cell membrane permeability, which allows CHX to inactivate enveloped viruses, such as the herpes simplex virus. However, it has a low virucidal activity on non-enveloped viruses, such as the human papillomavirus (HPV) [9].
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Antifungal Effect: CHX can reduce the amount of Candida albicans adhering to the tooth surface and the number of Candida albicans residing on soft tissues in vivo [10].
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Residual Effect: After a single rinse with a CHX-based solution, 30% can persist in saliva for up to 5 h and on the oral mucosa for up to 12 h [7]. 0.2% CHX mouthwash has greater substantivity on dental biofilm compared to salivary flora, even though the biofilm shows higher resistance to the antiseptic. This may be due to the biofilm's slower growth rate and its potential to act as a reservoir for antimicrobial agents [11].
CHX use can cause certain side effects. Among the most common effects are dry mouth (xerostomia), tooth discoloration with long-term use, and altered taste sensations (dysgeusia). Other less common side effects include a burning sensation and desquamation of the oral mucosa [12]. CHX presents certain limitations, amongst them bacterial resistance, causing the microorganisms to adapt and become resistant to CHX, rendering it less effective [13]. Prolonged exposure to CHX can lead to the development of resistance in certain oral microbial strains, and it has been suggested that CHX at high concentrations should only be used for short periods [14]. In the context of exploring new therapeutic alternatives to maintain the efficacy of chlorhexidine while reducing its side effects, a comparison between 0.12% chlorhexidine and 0.12% chlorhexidine combined with 0.10% cymenol showed no statistically significant difference between the two treatments for the clinical parameters evaluated, including plaque index (PI), gingival index (GI), bleeding index (BoP), pocket depth (PS), and clinical attachment loss (CAL). Although cymenol showed promising results in vitro for biofilm removal, its clinical efficacy did not surpass that of standard chlorhexidine. These results suggest the need to continue exploring other compounds to reduce the side effects of chlorhexidine while maintaining its effectiveness [15].
3.1.2 Cetylpyridinium Chloride
Cetylpyridinium chloride (CPC) is a monocationic quaternary ammonium compound with a substantivity of 3–5 h [6]. It has been suggested that it possesses antimicrobial activity facilitated by its positive charge, which promotes binding to negatively charged bacterial surfaces, thereby reducing bacterial adhesion to oral surfaces [16]. CPC significantly reduces plaque index and gingival index compared to placebo [16]. One limitation of this molecule is tooth staining, which depends on the dose used but remains less significant than with CHX [17].
3.1.3 Essential Oils
Essential oils (EO) are used in over-the-counter mouthwashes containing a fixed formula of two phenol-linked essential oils, thymol at 0.064% and eucalyptol at 0.092%, mixed with 0.042% menthol (an antiseptic) and 0.060% methyl salicylate (a cleansing agent) in an alcohol-based vehicle at 22% and 27% ethanol, depending on the flavor [18, 19].
The antimicrobial mechanisms of essential oils' action against bacteria are complex. At high concentrations, there is a cell wall disruption and precipitation of cellular proteins, while at lower concentrations, inactivation of essential enzymes occurs. Additionally, an anti-inflammatory action has been reported based on antioxidant activity [19, 20]. Essential oils appear to have antiplaque and anti-gingivitis effects compared to a placebo [19]. It has been suggested that essential oils possess antimicrobial and anti-inflammatory activities and would be the best alternative to CHX in controlling dental plaque and treating gingivitis. Amongst the limitations of essential oils are their strong taste and tooth discoloration [17]. The antiplaque effect of chlorhexidine (CHX), essential oils (EO), and cetylpyridinium chloride (CPC) was compared in a 3-week in vivo study. The results showed that chlorhexidine (CHX) achieved the best results, followed by essential oils (EO) [21]. A superior effect of essential oils (EO) compared to cetylpyridinium chloride (CPC) was found in a long-term study [22].
3.1.4 Triclosan
Triclosan is a non-ionic chlorinated aromatic compound that possesses functional groups representative of ethers and phenols. It has been suggested that it has antibacterial and antifungal properties [23], and also anti-inflammatory activity through its ability to inhibit fibroblast production of interleukin-1b-induced prostaglandin E2 [24].
Compared to a standard fluoride dentifrice, toothpastes containing triclosan as an adjunct seem to exert a positive effect on both gingivitis and dental plaque [24]. However, when compared to chlorhexidine, triclosan seems to have less antiplaque and antigingivitis activity [25]. Triclosan has been investigated for its possible endocrine-disrupting effects in humans over the last decades. In rodents, it consistently decreases serum T4 concentrations, likely by increasing hepatic catabolism of thyroid hormones [26]. The effects of triclosan on the human thyroid system at current exposure levels remain uncertain. Additionally, most studies used few blood samples, limiting their reliability, especially among pregnant women [26].
3.1.5 Povidone-Iodine
Povidone-iodine (PVP-I) is a broad-spectrum antimicrobial agent, economical and widely used, in addition to its rapid ability to eliminate microorganisms. However, its use is not recommended for patients with thyroid disorders or iodine allergies [27, 28].
The combination of polyvinylpyrrolidone (PVP-I) and chlorhexidine (CHX) can reduce the staining potential of CHX. However, this could also decrease the plaque reduction potential of CHX [29]. In a randomized clinical trial, the topical use of PVP-I solution and CHX gel on dental plaque growth was compared after 3 and 7 days in toddlers aged 24 to 36 months. It concluded that the effectiveness of CHX and PVP-I lasted only for 3 days, and that PVP-I was not superior to CHX in terms of plaque control in toddlers [28].
3.1.6 Delmopinol
Delmopinol is a low molecular weight amino alcohol substitute, which has been proven clinically effective in inhibiting dental plaque and gingivitis at a concentration of 0.2%. Its effectiveness is based on its ability to interfere with bacterial matrix formation, inhibit bacterial adhesion, and form a looser biofilm, which is easy to remove. This component binds to both hard and soft oral tissues as well as bacterial surfaces and affects several stages of dental biofilm formation [30].
Compared with a placebo, delmopinol has been shown to be effective in reducing plaque index and bleeding on probing (BOP) [31]. Compared to chlorhexidine (CHX), delmopinol has lower antimicrobial activity than CHX but causes fewer adverse effects [32]. Delmopinol has less antiplaque activity than CHX. However, both are equally effective in reducing gingivitis [33].
3.1.7 Natural Products
Natural products correspond to an extract of sanguinarine, an alkaloid obtained from the plant Sanguinaria canadensis, and other herbal ingredients such as chamomile, echinacea, sage, myrrh, ratanhia, and peppermint oil [3].
Plant extracts present a wide variety of metabolites with antimicrobial and antiviral properties in vitro. They also exhibit anti-inflammatory and antioxidant activity, which is beneficial for oral health. They act by reducing bacterial adhesion to both tooth surfaces and restoration materials and oxidative apoptosis of neutrophils [17]. The initial studies on mouthwashes made from natural products have shown promising antibacterial activity against gingival diseases [34, 35]. Plant-based toothpastes appear to be effective in reducing plaque. However, the quality of evidence seems to be low to recommend them as a substitute for conventional oral hygiene products (fluoride toothpaste, non-fluoride/non-herbal toothpaste, chlorhexidine mouth rinse, or non-herbal mouth rinse) [36]. Tulsi extract mouthwash (Holy Basil) reduces halitosis, plaque, and gingivitis, though it is less effective than chlorhexidine and hydrogen peroxide. However, its affordability and lack of side effects make it a cost-effective alternative, especially in public health settings with low patient compliance [37].
3.1.8 Hexetidine
Hexetidine (HEX) belongs to the group of pyrimidine derivatives. It is a broad-spectrum antiseptic, active in vitro and in vivo against gram-positive, gram-negative bacteria and yeast. However, its antimicrobial activity is short-lived [19]. Hexetidine mouthwashes are more effective than placebo mouthwashes in reducing dental plaque. However, they are less effective than chlorhexidine in reducing gingival inflammation and dental plaque [38].
3.1.9 Alexidine
Alexidine (ALX) is an antimicrobial agent belonging to the class of biguanides and contains ethylhexyl terminal groups. It has been reported that its structure promotes hydrophobic penetration into membrane lipids and electrostatic adherence to the negative sites of cell membranes, resulting in bactericidal activity [19]. Alexidine seems to be more effective in reducing plaque index and gingival inflammation than placebo [39]. Only this study has been conducted on alexidine and compared to a placebo, which significantly limits its prescription in routine practice [40].
3.1.10 Oxygenating Agents
Oxygenating agents (OA), such as hydrogen peroxide (H2O2), buffered sodium perborate, and peroxycarbonate, exert antimicrobial effects by releasing oxygen. Mouthwashes containing perborate can reduce the amount of dental plaque and delay the colonization and growth of anaerobic and gram-negative bacteria [17]. Mouthwashes based on H2O2 do not prevent the accumulation of dental plaque when used as short-term monotherapy [41].
3.1.11 Octenidine Dihydrochloride
Octenidine dihydrochloride is a cationic antimicrobial surfactant component. It exhibits antibacterial activity by disrupting the cell membrane of fungi, bacteria, and yeast due to its strong adherence to lipid components and binding to negatively charged microbial surfaces [42]. Rinsing two or three times a day with 0.1% octenidine for 30 to 60 s results in a reduction of plaque and gingivitis in addition to the inhibition of oral bacteria growth, compared to a placebo. Comparing octenidine dihydrochloride and chlorhexidine, both molecules showed similar antiplaque and anti-inflammatory activity. Furthermore, it is suggested that octenidine dihydrochloride could be an alternative to chlorhexidine in the treatment of gingivitis and plaque removal [42].
3.1.12 Metal Salts
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Stannous fluoride
Toothpastes containing stannous fluoride were introduced in 1950. They have a positive effect on calculus formation, dental plaque, gingival inflammation, and halitosis. However, they may cause extrinsic staining [43].
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Amine fluoride–stannous fluoride combination
Stannous fluoride (SnF2) and amine fluoride (AmF) have demonstrated bactericidal activity against bacteria. The combination of stannous fluoride (SnF2) and amine fluoride (AmF) results in the potentiation of their respective antibacterial effects, in addition to the stabilization of SnF2 by AmF [44]. AmF/SnF₂-containing products have beneficial clinical effects on plaque accumulation and gingival health after the placement of fixed orthodontic appliances. These beneficial effects may be more pronounced with prolonged and combined use of these products [45]. It also appears that the combination of AmF and SnF2 in mouthwashes is effective against halitosis [46]. Although they present some limitations like tooth staining, which represents the most common adverse effect [47, 48].
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Zinc salts
As standalone agents, they have limited effects on plaque. However, their formulation together can improve the substantivity and effectiveness of other active agents [49]. Statistically significant results regarding reductions in the gingival index and dental plaque were observed after using toothpastes containing zinc and arginine, compared to conventional fluoride toothpaste [50].
3.1.13 Detergents
Sodium lauryl sulfate (SLS) is the most commonly used detergent or surfactant (surface-active compound). SLS has demonstrated a substantivity of 5 to 7 h as well as a foaming property that can help remove dental plaque. However, there is not enough evidence to fully support this claim [3]. No significant difference was observed between toothpastes containing SLS and those without SLS regarding their effect on dental plaque and gingivitis [51]. Patients preferred the taste and foaming effect of toothpastes containing SLS. However, SLS has been associated with several adverse effects such as cheilitis, stomatitis, ulcerations, irritation or inflammation of the oral mucosa or dorsal tongue, as well as a burning sensation and desquamation of the oral mucosa [3, 52].
3.1.14 Other Antiseptic Molecules
Chlorine dioxide: Frequently used against halitosis. However, its antiplaque effects remain to be evaluated [53].
Sodium chlorite acidified: It has been suggested that this product has a similar activity to CHX in treating bacterial infections of the oral mucosa [54]. However, a potential for enamel erosion has been noted [55].
Ethyl lauroyl arginate (LAE): LAE hydrochloride is a cationic surfactant agent, active against bacteria and fungi, by altering membrane permeability. The initial results of short-term clinical studies have yielded contradictory results. A reduction in the bleeding index and plaque index was observed 3 months after LAE hydrochloride use in patients with periodontitis. These results are similar to those obtained with 0.12% CHX use [56]. On the other hand, LAE hydrochloride had a significant effect on plaque, but it was insufficient to prevent the onset of gingival inflammation [57].
3.2 Comparison of Antiseptic Molecules
Mouthwashes containing essential oils and chlorhexidine have been associated with a significantly greater positive effect on plaque index compared to mouthwashes containing delmopinol, alexidine, and cetylpyridinium chloride. Toothpastes containing copolymer triclosan and chlorhexidine have been associated with a significantly greater positive effect on plaque index compared to toothpastes containing stannous fluoride [58].
3.3 Indications
3.3.1 Single Preoperative Use
Antiseptic mouthwashes have been widely used before dental treatments, especially preoperatively by mouth rinsing, as they play an important role in reducing the number of microorganisms in the oral cavity. Mouthwashes containing chlorhexidine, essential oils, and cetylpyridinium chloride resulted in an average reduction in the number of colony-forming units (CFUs) by 64.8% compared to the control group (placebo) [59].
The use of preoperative mouthwashes may reduce the viral load of SARS-CoV-2. Thereby reducing the risk of cross-infection during patient treatment during the SARS-CoV-2 pandemic [60]. Similarly, approximately 12% of bacteremia cases could be prevented if mouth rinsing with a chlorhexidine-based mouthwash is performed before dental care [61].
3.3.2 Short-Term Use in Preventing Biofilm Formation When Mechanical Control Is Limited
Antiseptics are advised post-periodontal surgery to prevent mechanical contact with the treated area and reduce the risk of postsurgical infection. They are also recommended for patients with acute mucosal or gum infections, where pain hinders mechanical plaque control, as CHX mouthwashes effectively prevent biofilm formation. Antiseptic product use should be continued until mechanical biofilm control is resumed. Two molecules have proven their efficacy in reducing biofilm formation and gingival inflammation after surgical intervention, namely CHX and essential oils [62-64].
Prescribing CHX has been strongly recommended in implant surgery to optimize treatment success. Preoperative mouth rinsing with a 0.12% or 0.2% CHX solution to reduce bacterial load could be performed 7 to 10 days and immediately before surgery [65].
3.3.3 Short-Term Use for the Treatment of Periodontal Diseases
3.3.3.1 Treatment of Gingivitis and Periodontitis
According to the guidelines of the European Federation of Periodontology (EFP 2020), the use of CHX mouthwashes, for a short duration, in addition to mechanical debridement in the treatment of gingivitis and periodontitis, may be considered. The timing of administration is justified by the limited antimicrobial activity of chemical agents against organized biofilm [2, 66].
3.3.3.2 Treatment of Necrotizing Periodontal Diseases
It has been recommended to apply a gauze soaked in 0.12% CHX to remove the pseudomembrane and prescribe a mouthwash based on 0.12% CHX or rinsing with a mixture of equal parts 3% hydrogen peroxide and warm water in the case of necrotizing periodontal diseases [67].
3.3.3.3 Management of Peri-Implant Mucositis
At-home use of mouthwash containing essential oils, a toothpaste with triclosan/copolymer, and mouthwash with 0.03% CHX and 0.05% CPC yielded favorable clinical outcomes in the treatment of peri-implant mucositis [68].
3.3.3.4 Treatment of Peri-Implantitis
The use of various agents such as CHX, triclosan, stannous fluoride, essential oils, etc. has been suggested to optimize biofilm control and reduce the risk of peri-implant diseases [2].
Adjunctive application of CHX to mechanical debridement did not significantly improve clinical outcomes compared to mechanical debridement alone. Therefore, CHX application is unnecessary if debridement has been performed well and the patient adheres well to clinical guidelines [69]. This aligns with a 2023 updated systematic review suggesting that evidence on CHX's efficacy as an adjunct for peri-implant mucositis remains inconclusive. Similarly, due to the limited number of studies, no definitive conclusions can be drawn regarding the effect of CHX on peri-implantitis. Given the conflicting results, clinicians are advised to assess each case individually and consider the use of CHX until further evidence becomes available [70].
3.3.4 Long-Term Use for the Prevention of Biofilm Formation
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Patients undergoing orthodontic treatment may benefit from enhanced mechanical plaque control by incorporating antimicrobial agents such as amine fluoride/stannous fluoride or sanguinarine into mouth rinses combined with toothpaste or gels. Clinical studies [71, 72] evaluating this approach have reported significant benefits. However, the clinical relevance of these benefits may not always be clear [49]. In patients undergoing orthodontic treatment, the use of an antioxidant essential oil gel, an amine fluoride gel, a 0.4% stannous fluoride gel (with 98% availability of Sn²⁺), and a 2% chlorhexidine gel resulted in a significant improvement in gingivitis [73].
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Patients presenting with gingival hypertrophy: In such cases, mechanical control is limited, and mouth rinsing with a chlorhexidine-based solution has been shown to be beneficial [49];
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Patients undergoing periodontal maintenance therapy: Effective management of gingival inflammation primarily relies on the patient's mechanical removal of dental biofilm. In certain specific situations, the adjunctive use of antiseptics may be considered as part of a personalized therapeutic strategy, particularly for patients undergoing periodontal maintenance therapy. According to the EFP guidelines, adjunctive options may include toothpastes formulated with chlorhexidine, triclosan-copolymer, and stannous fluoride combined with sodium hexametaphosphate. Additionally, the use of mouth rinses containing chlorhexidine, essential oils, or cetylpyridinium chloride is recommended to further support the control of gingival inflammation in these patients [2].
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Halitosis: Various chemical agents and formulations have been evaluated to target two main objectives: antibacterial action and reducing the volatilization of odor compounds. Among the most evaluated agents are triclosan with zinc or copolymer [74] or chlorhexidine, especially when associated with zinc salts and CPC in a mouthwash formulation [75]. Another systematic review suggests that essential oils (EOs) and their constituents may have some benefits in reducing oral malodour, although the evidence is of low to very low certainty [76].
3.4 Timing of Antiseptic Prescription
The antimicrobial action of chemical agents may be restricted when facing an organized biofilm due to challenges related to penetration and action [2]. Mechanical debridement remains the only predictable method to disrupt dental biofilm [32]. Antimicrobial molecules must reach their target to deactivate the intertwined bacteria. The biofilm's glycocalyx protects bacteria from the host's humoral and cellular defense systems and the diffusion of antimicrobial agents to cellular targets, acting as a barrier by influencing the speed of molecule transport into the biofilm [77]. Due to oral bacteria organizing into biofilms, they are inherently less sensitive to antimicrobial agents. Therefore, disruption of the oral plaque biofilm is necessary for antimicrobial agents to be effective.
4 Conclusion
Antiseptics play an important role in improving periodontal health. Scientific studies have shown that chlorhexidine, essential oils, and povidone-iodine yield good results due to their ability to reduce gingival inflammation and improve plaque index compared to other antiseptics. Furthermore, other molecules, such as octenidine dihydrochloride, have also demonstrated effectiveness, although further studies are needed to broaden their field of use.
It is important to emphasize that the use of antiseptics should complement a rigorous oral hygiene routine and cannot replace it. The prescription of antiseptics should be based on the target objectives to ensure an appropriate dosage and duration while avoiding any excessive use.
Author Contributions
Lamiae Costo: conceptualization, writing – original draft, writing – review and editing. Mariam Mounsif: writing – review and editing, supervision, validation. Lamiaa Abdallaoui Maan: validation, supervision, visualization. Amal Bouziane: conceptualization, validation, visualization, supervision, methodology.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The authors have nothing to report.
