Alternatives to Antibiotics in Dentistry

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 40588

Special Issue Editor


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Guest Editor
Department of Periodontology, Laboratory of Oral Microbiology, School of Dental Medicine, University of Bern, Bern, Switzerland
Interests: antimicrobial therapy in dentistry; biofilms; antibiotics; alternatives to antibiotics
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Special Issue Information

Dear Colleagues,

Antibiotics (and antiseptics) are highly effective in killing (planktonic) bacteria. However, severe side effects affecting patients’ health may occur. Further, it is well known that the application of antibiotics is linked with the development of resistance.

Thus, there is an urgent need to search for alternatives. These alternatives to the commonly used antimicrobial antibiotics might be probiotics, natural products, photodynamic therapy, inhibitors of virulence factors, new developments in antimicrobials, etc. This Special Issue focuses on research that compares potential alternatives with commonly used antimicrobials in dentistry. In vitro studies, studies using animal models, and clinical studies (including pilot studies or case series) are welcome.

Prof. Dr. Sigrun Eick
Guest Editor

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Keywords

  • alternatives to antibiotics
  • oral infections
  • natural products
  • probiotics
  • photodynamic therapy
  • inhibition of bacterial virulence

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Published Papers (10 papers)

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Research

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11 pages, 7455 KiB  
Article
Inhibition of Candida albicans and Mixed Salivary Bacterial Biofilms on Antimicrobial Loaded Phosphated Poly(methyl methacrylate)
by Andrew R. Dentino, DongHwa Lee, Kelley Dentino, Arndt Guentsch and Mohammadreza Tahriri
Antibiotics 2021, 10(4), 427; https://doi.org/10.3390/antibiotics10040427 - 13 Apr 2021
Cited by 2 | Viewed by 2438
Abstract
Biofilms play a crucial role in the development of Candida-associated denture stomatitis. Inhibition of microbial adhesion to poly(methyl methacrylate) (PMMA) and phosphate containing PMMA has been examined in this work. C. albicans and mixed salivary microbial biofilms were compared on naked and [...] Read more.
Biofilms play a crucial role in the development of Candida-associated denture stomatitis. Inhibition of microbial adhesion to poly(methyl methacrylate) (PMMA) and phosphate containing PMMA has been examined in this work. C. albicans and mixed salivary microbial biofilms were compared on naked and salivary pre-conditioned PMMA surfaces in the presence or absence of antimicrobials (Cetylpyridinium chloride [CPC], KSL-W, Histatin 5 [His 5]). Polymers with varying amounts of phosphate (0–25%) were tested using four C. albicans oral isolates as well as mixed salivary bacteria and 24 h biofilms were assessed for metabolic activity and confirmed using Live/Dead staining and confocal microscopy. Biofilm metabolism was reduced as phosphate density increased (15%: p = 0.004; 25%: p = 0.001). Loading of CPC on 15% phosphated disks showed a substantial decrease (p = 0.001) in biofilm metabolism in the presence or absence of a salivary pellicle. Salivary pellicle on uncharged PMMA enhanced the antimicrobial activity of CPC only. CPC also demonstrated remarkable antimicrobial activity on mixed salivary bacterial biofilms under different conditions displaying the potent efficacy of CPC (350 µg/mL) when combined with an artificial protein pellicle (Biotene half strength). Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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12 pages, 481 KiB  
Article
Clinical and Microbiological Evaluation of Local Doxycycline and Antimicrobial Photodynamic Therapy during Supportive Periodontal Therapy: A Randomized Clinical Trial
by Raluca Cosgarea, Sigrun Eick, Ionela Batori-Andronescu, Søren Jepsen, Nicole B. Arweiler, Ralf Rößler, Torsten Conrad, Christoph A. Ramseier and Anton Sculean
Antibiotics 2021, 10(3), 277; https://doi.org/10.3390/antibiotics10030277 - 9 Mar 2021
Cited by 13 | Viewed by 2988
Abstract
The aim of this study was to evaluate the clinical and microbiological effects of subgingival instrumentation (SI) alone or combined with either local drug delivery (LDD) or photodynamic therapy (PDT) in persistent/recurrent pockets in patients enrolled in supportive periodontal therapy (SPT). A total [...] Read more.
The aim of this study was to evaluate the clinical and microbiological effects of subgingival instrumentation (SI) alone or combined with either local drug delivery (LDD) or photodynamic therapy (PDT) in persistent/recurrent pockets in patients enrolled in supportive periodontal therapy (SPT). A total of 105 patients enrolled in SPT were randomly treated as follows: group A (n = 35): SI +PDT and 7 days later 2nd PDT; group B (n = 35): SI+LDD; group C (n = 35): SI (control). Prior intervention, at 3 and 6 months after therapy, probing pocket depths, clinical attachment level, number of treated sites with bleeding on probing (n BOP), full mouth plaque and bleeding scores (gingival bleeding index, %BOP) were recorded. At the same time points, 8 periodontopathogens were quantitatively determined. All three treatments resulted in statistically significant improvements (p < 0.05) of all clinical parameters without statistically significant intergroup differences (p > 0.05). Several bacterial species were reduced in both test groups, with statistically significantly higher reductions for LDD compared to PDT and the control group. In conclusion, the present data indicate that: (a) In periodontal patients enrolled in SPT, treatment of persistent/recurrent pockets with SI alone or combined with either PDT or LDD may lead to comparable clinical improvements and (b) the adjunctive use of LDD appears to provide better microbiological improvements for some periodontal pathogens than SI alone or combined with PDT. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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10 pages, 1411 KiB  
Article
Effects of the Licorice Isoflavans Licoricidin and Glabridin on the Growth, Adherence Properties, and Acid Production of Streptococcus mutans, and Assessment of Their Biocompatibility
by Katy Vaillancourt, Geneviève LeBel, Geneviève Pellerin, Amel Ben Lagha and Daniel Grenier
Antibiotics 2021, 10(2), 163; https://doi.org/10.3390/antibiotics10020163 - 5 Feb 2021
Cited by 17 | Viewed by 3549
Abstract
Pharmacological studies have linked a number of human health benefits with licorice due to its anticancer, anti-inflammatory, anti-oxidant, and antimicrobial properties. The aim of this study was to investigate the effects of licoricidin and glabridin, two major licorice isoflavans, on growth and virulence [...] Read more.
Pharmacological studies have linked a number of human health benefits with licorice due to its anticancer, anti-inflammatory, anti-oxidant, and antimicrobial properties. The aim of this study was to investigate the effects of licoricidin and glabridin, two major licorice isoflavans, on growth and virulence properties (biofilm formation, acid production, dextran production, adherence) of the cariogenic bacterium Streptococcus mutans. Moreover, the biocompatibility of these licorice compounds was assessed in an in vitro model of oral keratinocytes. We used a broth microdilution assay to show that licoricidin and glabridin exhibit a marked antibacterial activity against S. mutans. Glabridin and, to a lesser extent, licoricidin reduced the biofilm viability of S. mutans. In addition, glabridin decreased the production of dextran by S. mutans. The two licorice isoflavans attenuated the adherence of S. mutans to a saliva-coated hydroxylapatite surface, and reduced acid production from glucose. Lastly, depending on the concentrations tested, the two licorice isoflavans showed no or low toxicity toward oral keratinocytes. Within the limitations of this study, our data suggest that licoricidin and glabridin may be promising agents for controlling dental caries. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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9 pages, 3513 KiB  
Article
Antimicrobial Potential of Strontium Hydroxide on Bacteria Associated with Peri-Implantitis
by Hatem Alshammari, Jessica Neilands, Gunnel Svensäter and Andreas Stavropoulos
Antibiotics 2021, 10(2), 150; https://doi.org/10.3390/antibiotics10020150 - 3 Feb 2021
Cited by 16 | Viewed by 2401
Abstract
Background: Peri-implantitis due to infection of dental implants is a common complication that may cause significant patient morbidity. In this study, we investigated the antimicrobial potential of Sr(OH)2 against different bacteria associated with peri-implantitis. Methods: The antimicrobial potential of five [...] Read more.
Background: Peri-implantitis due to infection of dental implants is a common complication that may cause significant patient morbidity. In this study, we investigated the antimicrobial potential of Sr(OH)2 against different bacteria associated with peri-implantitis. Methods: The antimicrobial potential of five concentrations of Sr(OH)2 (100, 10, 1, 0.1, and 0.01 mM) was assessed with agar diffusion test, minimal inhibitory concentration (MIC), and biofilm viability assays against six bacteria commonly associated with biomaterial infections: Streptococcus mitis, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Escherichia coli, and Fusobacterium nucleatum. Results: Zones of inhibition were only observed for, 0.01, 0.1, and 1 mM of Sr(OH)2 tested against P. gingivalis, in the agar diffusion test. Growth inhibition in planktonic cultures was achieved at 10 mM for all species tested (p < 0.001). In biofilm viability assay, 10 and 100 mM Sr(OH)2 showed potent bactericidal affect against S. mitis, S. epidermidis, A. actinomycetemcomitans, E. coli, and P. gingivalis. Conclusions: The findings of this study indicate that Sr(OH)2 has antimicrobial properties against bacteria associated with peri-implantitis. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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11 pages, 910 KiB  
Article
Effect of a Berry Polyphenolic Fraction on Biofilm Formation, Adherence Properties and Gene Expression of Streptococcus mutans and Its Biocompatibility with Oral Epithelial Cells
by Mariem Souissi, Amel Ben Lagha, Kamel Chaieb and Daniel Grenier
Antibiotics 2021, 10(1), 46; https://doi.org/10.3390/antibiotics10010046 - 5 Jan 2021
Cited by 10 | Viewed by 3349
Abstract
The ability of Streptococcus mutans to adhere to oral surfaces and form biofilm is a key step in the tooth decay process. The aim of this study was to investigate a berry (wild blueberry, cranberry, and strawberry) polyphenolic fraction, commercialized as Orophenol® [...] Read more.
The ability of Streptococcus mutans to adhere to oral surfaces and form biofilm is a key step in the tooth decay process. The aim of this study was to investigate a berry (wild blueberry, cranberry, and strawberry) polyphenolic fraction, commercialized as Orophenol®, for its antibacterial, anti-biofilm, and anti-adhesion properties on S. mutans. Moreover, the biocompatibility of the fraction with human oral epithelial cells was assessed. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins made up 10.71%, 19.76%, and 5.29% of the berry polyphenolic fraction, respectively, as determined by chromatography and mass spectrometry. The berry polyphenolic preparation dose-dependently inhibited S. mutans biofilm formation while not reducing bacterial growth. At concentrations ranging from 250 to 1000 µg/mL, the fraction inhibited the adhesion of S. mutans to both saliva-coated hydroxyapatite and saliva-coated nickel–chrome alloy. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that incubating S. mutans with the berry polyphenolic fraction was associated with a reduced expression of luxS gene, which regulates quorum sensing in S. mutans. The berry fraction did not show any significant cytotoxicity in an oral epithelial cell model. In conclusion, Orophenol®, which is a mixture of polyphenols from wild blueberry, cranberry and strawberry, possesses interesting anti-caries properties while being compatible with oral epithelial cells. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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13 pages, 631 KiB  
Article
Non-Surgical Periodontal Therapy with Adjunctive Amoxicillin/Metronidazole or Metronidazole When No Aggregatibacter actinomycetemcomitans Is Detected—A Randomized Clinical Trial
by Holger F. R. Jentsch, Martin Dietrich and Sigrun Eick
Antibiotics 2020, 9(10), 686; https://doi.org/10.3390/antibiotics9100686 - 9 Oct 2020
Cited by 7 | Viewed by 3678
Abstract
Background: The aim was to compare two different systemic antibiotics regimens adjunctive to non-surgical periodontal therapy when Aggregatibacter actinomycetemcomitans was not detected in the subgingival biofilm. Methods: A total of 58 patients with periodontitis and with no A. actinomycetemcomitans in the subgingival biofilm [...] Read more.
Background: The aim was to compare two different systemic antibiotics regimens adjunctive to non-surgical periodontal therapy when Aggregatibacter actinomycetemcomitans was not detected in the subgingival biofilm. Methods: A total of 58 patients with periodontitis and with no A. actinomycetemcomitans in the subgingival biofilm were treated with full-mouth subgingival instrumentation and either metronidazole (MET; n = 29) or amoxicillin/metronidazole (AMX/MET; n = 29). Probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded at baseline, as well as after three and six months. Subgingival biofilm and gingival crevicular fluid were collected and analyzed for major periodontopathogens and biomarkers. Results: PD, CAL and BOP improved at 3 and 6 months (each p < 0.001 vs. baseline) with no difference between the groups. Sites with initial PD ≥ 6 mm also improved in both groups after 3 and 6 months (p < 0.001) with a higher reduction of PD in the AMX/MET group (p < 0.05). T. forsythia was lower in the AMX/MET group after 3 months (p < 0.05). MMP-8 and IL-1β were without significant changes and differences between the groups. Conclusion: When A. actinomycetemcomitans was not detected in the subgingival biofilm, the adjunctive systemic use of amoxicillin/metronidazole results in better clinical and microbiological outcomes of non-surgical periodontal therapy when the application of systemic antibiotics is scheduled. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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14 pages, 1596 KiB  
Article
Antimicrobial Effect of Natural Berry Juices on Common Oral Pathogenic Bacteria
by Stefan Kranz, André Guellmar, Philipp Olschowsky, Silke Tonndorf-Martini, Markus Heyder, Wolfgang Pfister, Markus Reise and Bernd Sigusch
Antibiotics 2020, 9(9), 533; https://doi.org/10.3390/antibiotics9090533 - 24 Aug 2020
Cited by 26 | Viewed by 4673
Abstract
(1) Background: Antimicrobial agents such as chlorhexidine (CHX) are commonly used in oral plaque control. However, sometimes those agents lack antimicrobial efficiency or cause undesired side effects. To identify alternative anti-infective agents, the present study investigated the antibacterial activity of all-fruit juices derived [...] Read more.
(1) Background: Antimicrobial agents such as chlorhexidine (CHX) are commonly used in oral plaque control. However, sometimes those agents lack antimicrobial efficiency or cause undesired side effects. To identify alternative anti-infective agents, the present study investigated the antibacterial activity of all-fruit juices derived from blackcurrant, redcurrant, cranberry and raspberry on common oral pathogenic gram-positive and gram-negative bacteria (Streptococcus mutans, Streptococcus gordonii, Streptococcus sobrinus, Actinomyces naeslundii, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Enterococcus faecalis). (2) Methods: Antibacterial efficiency was evaluated by agar diffusion assay and in direct contact with bacteria in planktonic culture. Furthermore, cytotoxicity on human gingival fibroblasts was determined. (3) Results: Blackcurrant juice was most efficient at suppressing bacteria; followed by the activity of redcurrant and cranberry juice. Raspberry juice only suppressed P. gingivalis significantly. Only high-concentrated blackcurrant juice showed minimal cytotoxic effects which were significantly less compared to the action of CHX. (4) Conclusion: Extracts from natural berry juices might be used for safe and efficient suppression of oral pathogenic bacterial species. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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Review

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21 pages, 722 KiB  
Review
Leaves and Fruits Preparations of Pistacia lentiscus L.: A Review on the Ethnopharmacological Uses and Implications in Inflammation and Infection
by Egle Milia, Simonetta Maria Bullitta, Giorgio Mastandrea, Barbora Szotáková, Aurélie Schoubben, Lenka Langhansová, Marina Quartu, Antonella Bortone and Sigrun Eick
Antibiotics 2021, 10(4), 425; https://doi.org/10.3390/antibiotics10040425 - 12 Apr 2021
Cited by 48 | Viewed by 6391
Abstract
There is an increasing interest in revisiting plants for drug discovery, proving scientifically their role as remedies. The aim of this review was to give an overview of the ethnopharmacological uses of Pistacia lentiscus L. (PlL) leaves and fruits, expanding the search for [...] Read more.
There is an increasing interest in revisiting plants for drug discovery, proving scientifically their role as remedies. The aim of this review was to give an overview of the ethnopharmacological uses of Pistacia lentiscus L. (PlL) leaves and fruits, expanding the search for the scientific discovery of their chemistry, anti-inflammatory, antioxidative and antimicrobial activities. PlL is a wild-growing shrub rich in terpenoids and polyphenols, the oil and extracts of which have been widely used against inflammation and infections, and as wound healing agents. The more recurrent components in PlL essential oil (EO) are represented by α-pinene, terpinene, caryophyllene, limonene and myrcene, with high variability in concentration depending on the Mediterranean country. The anti-inflammatory activity of the oil mainly occurs due to the inhibition of pro-inflammatory cytokines and the arachidonic acid cascade. Interestingly, the capacity against COX-2 and LOX indicates PlL EO as a dual inhibitory compound. The high content of polyphenols enriching the extracts provide explanations for the known biological properties of the plant. The protective effect against reactive oxygen species is of wide interest. In particular, their anthocyanins content greatly clarifies their antioxidative capacity. Further, the antimicrobial activity of PlL oil and extracts includes the inhibition of Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida spp. In conclusion, the relevant scientific properties indicate PlL as a nutraceutical and also as a therapeutic agent against a wide range of diseases based on inflammation and infections. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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20 pages, 723 KiB  
Review
The Antimicrobial Effect of Cold Atmospheric Plasma against Dental Pathogens—A Systematic Review of In-Vitro Studies
by Gert Jungbauer, Dominick Moser, Steffen Müller, Wolfgang Pfister, Anton Sculean and Sigrun Eick
Antibiotics 2021, 10(2), 211; https://doi.org/10.3390/antibiotics10020211 - 20 Feb 2021
Cited by 35 | Viewed by 4925
Abstract
Interest in the application of cold atmospheric plasma (CAP) in the medical field has been increasing. Indications in dentistry are surface modifications and antimicrobial interventions. The antimicrobial effect of CAP is mainly attributed to the generation of reactive oxygen and reactive nitrogen species. [...] Read more.
Interest in the application of cold atmospheric plasma (CAP) in the medical field has been increasing. Indications in dentistry are surface modifications and antimicrobial interventions. The antimicrobial effect of CAP is mainly attributed to the generation of reactive oxygen and reactive nitrogen species. The aim of this article is to systematically review the available evidence from in-vitro studies on the antimicrobial effect of CAP on dental pathogens. A database search was performed (PubMed, Embase, Scopus). Data concerning the device parameters, experimental set-ups and microbial cultivation were extracted. The quality of the studies was evaluated using a newly designed assessment tool. 55 studies were included (quality score 31–92%). The reduction factors varied strongly among the publications although clusters could be identified between groups of set pathogen, working gases, and treatment time intervals. A time-dependent increase of the antimicrobial effect was observed throughout the studies. CAP may be a promising alternative for antimicrobial treatment in a clinically feasible application time. The introduced standardized protocol is able to compare the outcome and quality of in-vitro studies. Further studies, including multi-species biofilm models, are needed to specify the application parameters of CAP before CAP should be tested in randomized clinical trials. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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28 pages, 2817 KiB  
Review
Microbial Association with Genus Actinomyces in Primary and Secondary Endodontic Lesions, Review
by Mario Dioguardi, Cristian Quarta, Mario Alovisi, Vito Crincoli, Riccardo Aiuto, Rolando Crippa, Francesca Angiero, Enrica Laneve, Diego Sovereto, Alfredo De Lillo, Giuseppe Troiano and Lorenzo Lo Muzio
Antibiotics 2020, 9(8), 433; https://doi.org/10.3390/antibiotics9080433 - 22 Jul 2020
Cited by 11 | Viewed by 3472
Abstract
The main reason for root canal treatment failure is the persistence of microorganisms after therapy, or the recontamination of the root canal system due to an inadequate seal. In the mouth, Actinomyces spp. constitute a significant part of the normal flora, which is [...] Read more.
The main reason for root canal treatment failure is the persistence of microorganisms after therapy, or the recontamination of the root canal system due to an inadequate seal. In the mouth, Actinomyces spp. constitute a significant part of the normal flora, which is indicative of their ability to adhere to oral tissue and resist cleansing mechanisms, such as salivary flow. This review, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), aims to clarify the prevalence of microbial genera that are associated with the genus Actinomyces in primary and secondary endodontic infections (primary outcome), and to identify the most prevalent species of the Actinomyces genus in endodontic lesions (secondary outcome). A total of 11 studies were included in the qualitative and quantitative analysis, and a total of 331 samples were analyzed. Bacteria of the genus Actinomyces were found in 58 samples, and 46 bacterial genera were detected in association with bacteria of the genus Actinomyces. Bacteria of the genus Streptococcus and Propionibacterium were those most frequently associated with Actinomyces in the endodontic lesions considered, and Actinomyces israelii was the most frequently involved species. Full article
(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)
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