Clin Dent Rev (2017) 1:11 https://doi.org/10.1007/s41894-017-0011-3 TREATMENT Antimicrobials in caries prevention Ece Eden 1 Received: 30 August 2017 / Accepted: 12 September 2017 / Published online: 26 September 2017 Ó Springer International Publishing AG 2017 Abstract Regularly removing biofilm and controlling risk factors are essential for managing dental caries. As an alternative way of preventing and managing the disease, antimicrobial agents to counter the bacterial component in the caries process were investigated. However, these agents are considered to have limited value and are therefore restricted to special care groups. This review summarises the effect of antimicrobial agents such as chlorhexidine, iodine and ozone as well as the antimicrobial effect of some natural products on managing carious lesion development. Keywords Caries Prevention Chlorhexidine Ozone Iodine Quick reference/description Dental caries is characterized by the demineralization of the hard dental tissues through acid that results from fermentation of free sugars by certain microorganisms in dental biofilm. Traditionally, an important factor in managing dental caries has been the reduction and elimination of a few specific pathologic microorganisms. The acid-producing effect of these pathologic microorganisms can be reduced or eliminated by removing the biofilm through mechanical or electric brushing with fluoride-containing toothpaste. Antiseptic and antimicrobial agents or antimicrobials can reduce cariogenic microorganisms non-mechanically. Antimicrobials suppress pathological oral microorganisms and favor the oral health of both soft gingival and hard dental tissues. They either kill or control the proliferation of the & Ece Eden eceeden@yahoo.com 1 Department of Pedodontics, School of Dentistry, Ege University, 35100 Bornova, İzmir, Turkey
11 Page 2 of 6 Clin Dent Rev (2017) 1:11 microorganisms and eliminate the extensive inflammatory response in gingival tissues. These agents are considered to have limited value in caries prevention and are therefore restricted to special care groups such as young children with early childhood caries, adolescents under orthodontic treatment or elderly with root caries as an adjunct to manage dental caries. Overview Different antimicrobials that are used in caries management are set out in Table 1. Procedure Chlorhexidine Chlorhexidine is a biguanide drug accepted as gold standard for managing gingivitis. It is adsorbed onto the cell walls of microorganisms, and is bacteriostatic at low concentration and bactericidal at higher concentrations. It is effective against Streptococcus mutans and Lactobacilli. Usually delivered as mouthrinse, gel or varnish, chlorhexidine mouthrinse is prescribed as 10 ml of 0.2% or 15 ml of 0.12% chlorhexidine-containing rinse twice a day for a maximum of 2 weeks. In gel form, chlorhexidine can be applied as a paste at home or in trays in the dental clinic. Frequency of use is 3 4 times daily for 2 days or daily for 10 14 days. For chlorhexidine varnish, application at 3-month intervals or 2 3 applications at the start and follow-up application after 1 or 3 months is needed. Chlorhexidine is widely used for reducing the apparent presence of the high bacterial component in high-caries-risk patients like children with severe early childhood caries, adolescents receiving orthodontic treatment and elderly patients with hyposalivation. Other indications include root caries and prevention of plaque accumulation. Table 2 shows examples of commercial chlorhexidine products. Ozone Ozone is a triatomic molecule that consists of three oxygen molecules having high oxidation potential. It oxidates bacteria, viruses and fungi. Ozone gas is delivered using ozone generators (Table 3). As ozone is highly toxic at high concentrations, safety limits of 0.3 ppm for 15 min (US Occupational Safety and Health Administration, OSHA) and up to 0.1 ppm inhalation without a clear threshold (National Institute for Occupational Safety and Health, NIOSH) is applied when ozone is used in dentistry. It is used as an antimicrobial for cavities, root canals, and periodontal pockets, implant surgery and root caries as ozone works better on the biofilm positioned over the dentine surface. However, evidence is scarce and standard concentration and application methods need further research.
Clin Dent Rev (2017) 1:11 Page 3 of 6 11 Table 1 Different antimicrobials that are used in caries management Treatment Formulation Indications Advantages Disadvantages Mechanism of action I. Chlorhexidine Mouthrinse (Chlorhexidine gluconate) Gel Varnish II. Ozone Gas In water or oil III. Iodine (Povidone Iodine) Mouthrinse Solution gargle Gingivitis Early childhood caries Adolescents receiving orthodontic treatment Root caries Elderly patients with hyposalivation To reduce dental plaque Antimicrobial for: Cavities Root canals Periodontal pockets Root caries Implant surgery Severe and early childhood caries Postsurgical medicament IV. Triclosan Toothpaste Caries prevention Prevention of plaque accumulation V. Natural antimicrobials (essential oils and ethanol) Mouthrinse Gingivitis Prevention of plaque accumulation Easily available Tooth staining Taste disorders Stimulates blood circulation and immune response Easily available Irritation Staining Effective against both Grampositive and Gram-negative bacteria No side-effects No drug resistance No side effects Toxic in high concentrations Not cost effective Concerns on health need further research Difficult to purify crude form Difficult to explain their structure and determine molecular formula Depending upon drug concentration: bacteriostatic or bactericidal Oxidates bacteria, viruses, fungi Antiseptic Antimicrobial Antiplaque Antimicrobial Antiplaque
11 Page 4 of 6 Clin Dent Rev (2017) 1:11 Table 2 Examples of commercial chlorhexidine products Product Concentration Formulation Concool F a Peridex b Corsodyl c Cervitec Gel d TePe Gingival Gel e Cervitec Plus d Chlorzoin f Prevora g BioC h EC 40 h * NaF sodium fluoride a Weltec, Osaka, Japan b 3M Espe Dental Products, USA 0.05% 0.12% 0.2% 0.2% (?0.2% NaF*) 0.2% (?0.32% NaF*) 1% (?1% thymol) 10% 10% 20% 35% Mouthrinse Gel Varnish c GlaxoSmithKline Consumer Healthcare, Brentford, TW8 9GS, UK d Ivoclar Vivadent, Schaan, Liechtenstein e TePe, Munhygienprodukter AB, Malmö, Sweden f Knowell, Therapeutic Technologies, Toronto, Canada g CHX Technologies Europe Limited, Hampshire, UK h Biodent, Nijmegen, Netherlands Table 3 Ozone generators used in dentistry Ozone Generator Ozone concentration produced HealOzone a 2100 ppm as 0.052%, v/v in air at a rate of 13.33 ml/s Ozonytron X, XL, XP b 1000 100,000 Prozone c 140 ppm at 2 L/min v/v volume/volume a KaVo GmbH, Biberach, Germany b MIO International Ozonytron GmbH, Germany c WgH, Germany Iodine Iodine is altered by adding polyvinyl-pyrrolidone (PVP) to form povidone iodine (PI) to increase its solubility in water and reduce irritation and staining. It is an antiseptic used for controlling severe and early childhood caries and as a postsurgical medicament. Some commercial products of iodine are listed in Table 4. Triclosan Triclosan (2,4,4 0 -trichloro-2 0 -hydroxydiphenyl ether) is a bisphenolic and noncationic agent. It is effective against both Gram-positive and Gram-negative bacteria.
Clin Dent Rev (2017) 1:11 Page 5 of 6 11 Table 4 Examples of commercial products of iodine Product Concentration Formulation Popiyodon gargle a 7% Mouthrinse Betadine b 1% Solution gargle a Yoshida Pharmaceuticals Co., Ltd, Saitama, Japan b Mundipharma Distribution GmbH, Philippines Table 5 List of natural antimicrobials Plants and plant products Macelignan Tea (Camellia sinensis) Cranberry (Vaccinium macrocarpon) Cacao Coffee Barley coffee Aloe Vera Essential oils (morrisonii oil, tea-tree oils etc.) Animal products Chitosan Propolis For enhanced sustainability, it is used in toothpastes with a copolymer of polyvinylmethylether/maleic acid (PVM/MA), in combination with zinc citrate or sodium fluoride. Long-term use of toothpastes containing triclosan is safe. Triclosan is used for prevention of caries and plaque accumulation. Natural antimicrobials Secondary metabolites of natural products may have anti-caries properties and are classified into three groups: Phenolic compounds with benzene rings, hydrogen and oxygen. Terpenoids made up of carbon and hydrogen. Alkaloids that contain nitrogen. Many plant species and animal products have been reported to have an antimicrobial effect (Table 5), but further studies are needed to have successful novel products with a therapeutically relevant compound from nature. For establishing the safety of natural products, the US Food and Drug Administration (FDA) assigns substances to the GRAS (generally recognized as safe) list. Essential oils are used for reducing gingivitis and plaque accumulation but their anti-caries effect has not been investigated. The commercial product Listerine, which contains essential oils (EO) and ethanol, has a strong disinfection effect on cariogenic bacteria within the biofilm.
11 Page 6 of 6 Clin Dent Rev (2017) 1:11 Pitfalls and complications Bacterial resistance may occur after long-term use of antimicrobials. Xerostomia may worsen in patients taking polypharmacy with long-term use of antimicrobial mouthrinse. Chemical antimicrobials causes side effects such as extrinsic staining or taste disorders. Maintaining a stable minimum inhibitory concentration (MIC) of the drug in the oral cavity is difficult. Mouthrinses cannot be used in young pediatric patients because of the high risk of swallowing the liquid. Ozone generators have safety issue. Evacuation of the ozone gas by using adequate suction for all ozone generators is very important for the safety of the patient and the dental staff. Ozone is not a cost-effective adjunct in management of caries. Iodine causes irritation and staining. Using crude natural extracts in caries management presents problems due to their complex nature, which makes them difficult to purify, elucidate their structure and determine their molecular formula. Also, the natural extract should contain bioactive molecules in proper concentration. The chemical composition of naturally derived products may vary, depending on the geographic region, season and biological diversity that will alter effectiveness. Further reading 1. Eden E (ed) Evidence-based caries prevention. Antimicrobials in caries prevention. doi:10.1007/978-3- 319-40034-1_5 2. Rabe P, Twetman S, Kinnby B, Svensäter G, Davies JR (2015) Effect of fluoride and chlorhexidine digluconate mouthrinses on plaque biofilms. Open Dent J 9:106 111 3. Van Strydonck DA, Slot DE, Van der Velden U, Van der Weijden F (2012) Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. J Clin Periodontol 39(11):1042 1055 4. Walsh T, Oliveira-Neto JM, Moore D (2015) Chlorhexidine treatment for the prevention of dental caries in children and adolescents. Cochrane Database Syst Rev 4:CD008457 5. Medeiros PB, Otero SA, Frencken JE, Bronkhorst EM, Leal SC (2015) Effectiveness of an oral health program for mothers and their infants. Int J Paediatr Dent 25(1):29 34