Original study - ZZI 01/2009

Essential oils: antimicrobial effects and potential treatment options in dental implantology

P.H. Warnke1,2, R. Podschun3, J. Wiltfang1, I.N.G. Springer1, E. Behrens1, S.T. Becker1

Due to the steadily increasing numbers of dental implants placed, the number of peri-implant infections is also growing. To date, there is no standard and generally accepted regimen for treating peri-implant infections. The search for alternative treatment options is ongoing. This pilot study focuses on the antimicrobial effects of essential oils as their antimicrobial and anti-inflammatory effects have recently been highlighted in literature. The results may offer potential treatment options for peri-implant infections based on natural essential oils. Eucalyptus, tea tree, white thyme, lemon, lemongrass, clove bud oil and oil combinations were tested in the agar diffusion test against clinically relevant strains and multi-resistant nosocomial isolates. Ethanol, povidone iodine, chlorhexidine as well as olive and paraffin oil served as controls. The essential oils tested showed clear antimicrobial effects against staphylococci, streptococci and candida. In particular, the absolute impact on multi-resistant strains such as MRSA and Candida krusei should be stressed. The anti-inflammatory properties of essential oils may be advantageous in dental implantology compared to classic antiseptics. Essential oils can be produced naturally and cost-effectively. If the suspected antimicrobial effects can be confirmed against the dominant strains in peri-implant infections, essential oils may offer an alternative in the local treatment of these infections.

 

Keywords: Essential oils, antimicrobial, peri-implant infection, multi-resistant strains, MRSA, antiseptics

Introduction

The insertion of dental implants is a routine procedure in dentistry nowadays. Treatment with dental implants allows outstanding aesthetic reconstruction with optimal masticatory function following tooth loss. Modern dental implants usually have bioinert titanium surfaces and the healing rates are over 97 % [25].

However, peri-implant infections, similar to periodontal pocket infections with natural teeth, are a potential problem. Peri-implant infections involve the tissue surrounding the implant. A distinction is made between “peri-implant mucositis“ and “peri-implantitis“. The former consists of reversible inflammation of the soft tissue. When chronic inflammation progresses with marked submarginal accumulation of plaque, peri-implantitis can develop; this is characterized by irreversible progressive bone loss in addition to the soft tissue infection. The development of peri-implant infection does not necessarily mean that implant loss is inevitable if provided treatment is commenced in time. Osseointegrated oral implants differ from titanium joint prostheses in orthopedic surgery. If the latter become infected, they must often be removed despite broad-spectrum antibiotic therapy for several weeks [19].

Different regimens for treating peri-implant infections have been presented at specialist conferences, some of them controversial, so that to date there is no uniform, standardized and generally accepted treatment regimen. Whereas non-specific broad-spectrum antibiotic therapy (e. g. tetracycline and metronidazole) was employed for several weeks up to the end of the 1990s, as in the case of infected orthopedic implants, a regimen based on the treatment of natural dental pocket infections and involving local insertion of anti-inflammatory medications following curetting plus disinfectant oral rinses (e. g. chlorhexidine) daily for several weeks is now accepted [21]. Laser photodynamic or photothermal elimination of the bacteria flora appears promising [22] but is not available to every clinician, so it may be too specialized to be considered a standard treatment. Peri-implant colonization with pathogenic micro-organisms is usually the cause of the infection, but this can be encouraged by other causal factors, e. g. a lack of keratinized gingiva. In these cases, antiseptic treatment on its own is insufficient and complex treatment with several sessions to eliminate all the promoting factors becomes necessary.

Treatment failures due to poor patient compliance are not rare and are an underestimated problem. The best treatment will not be effective if the patient does not cooperate. This often results in the infection becoming chronic. The clinician often switches to local and systemic antibiotic therapy in order to preserve the valuable prosthetic implant constructions. The high costs of a prosthetic restoration, which must be met privately, can be a source of tension between dentist and patient if loss appears imminent. The patient often looks for mistakes in the quality of the work (“it cost a lot so it has to last a long time“). Thus, the patient’s cleaning problem becomes a problem for the dentist and possibly for his reputation, which leads to early initiation of aggressive antibiotic therapy. This produces an increased risk of selection of antibiotic-resistant micro-organisms, which may even cause life-threatening abscesses [3]. In orthopaedic surgery, the long-term use of antibiotics has already led to a substantial increase in antibiotic resistant pathogens associated with artificial joint implant infections [1].

Accordingly, there is great interest in developing new regimens for the treatment of peri-implant infections. These should

1. effectively combat microbiological colonization of the implant with pathological flora,

2. limit the development of antibiotic-resistant micro-organisms,

3. prevent selection of secondary pathological flora (e. g. secondary candida infections after antibiotic treatment),

4. have anti-inflammatory characteristics in order to reduce destructive endogenous cytokines and enzymes as a result of inflammation,

5. if possible promote tissue regeneration in the sense of restitutio ad integrum.

 

Antimicrobial and anti-inflammatory characteristics are attributed to essential oils such as eucalyptus and tea tree oil [17]. These are employed frequently in traditional or complementary medicine, but are not accepted as a medication by the majority of clinicians with their roots in orthodox medicine. In contrast, the trust patients place in natural remedies is often re-markably striking. These oils are also experiencing a boom as cosmetics and can already be found, for instance, in oral rinses such as Listerine (www.listerine.com, McNEIL-PPC, USA) and toothpastes (Fig. 1). This induced us to conduct a pilot study of the antimicrobial effectiveness of a selection of essential oils against clinically relevant micro-organisms using scientifically accepted microbiological methods.

The aim is to develop potential new regimens for the treatment of peri-implant infections possibly based on essential oils.

 

Material and methods

The following essential oils, which are reputed in alternative medicine literature to have antimicrobial characteristics, were tested using in-vitro microbiological methods: eucalyptus oil, tea tree oil, thyme oil, lemon oil, lemongrass oil and clove bud oil. Only pure Australian oils obtained directly from Australian manufacturers were used, which were supplied without synthetic perfumes or solvents. Three oil mixtures and oral rinse formulations containing essential oils were also tested. These included our own oil combination, a mixture of several pure oils, which was designated KMPT Mix. KMPT Mix is a mixture of eucalyptus oil, tea tree oil, lemongrass oil, lemon oil, clove bud oil and thyme oil dissolved in 30 % ethanol. The other two mixtures were Liste-rine and Salviathymol (MADAUS GmbH, Cologne, Germany).

The controls employed in the study were standard water-soluble antiseptics such as ethanol (70 %), povidone iodine and chlorhexidine 0.1 %. The other lipophilic controls were olive oil and liquid paraffin, which were not expected to have any antimicrobial activity.

 

Bacterial and candida strains

The test substances were tested against strains of clinically relevant species (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus haemolyticus and Candida albicans) using the agar diffusion test. Clinical problem strains such as isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida krusei were also tested. Each test was performed in duplicate.

Agar diffusion test

A colony of the micro-organisms to be tested was stirred into 10 ml physiological saline. 2 ml of the solution was added to nutrient agar (depending on the strain: Mueller-Hinton agar, Columbia agar with 5 % sheep blood, Sabouraud agar plus glucose), distributed uniformly and 1 ml of the solution was pipetted.

After drying the inoculated agar plates, test discs (Antimicrobial Susceptibility TEST DISCS from OXOID, diameter 6 mm) were placed in the centre of the plates using sterile forceps and 10 µl of the test oil was placed on them. The agar plates were then incubated for 18 hours at 37 °C. Streptococcal test strains underwent microaerophilic incubation.

Following this, the diameters of the growth-free inhibition zones that had occurred around the test discs if the test substance exhibited antimicrobial activity were measured. Inhibition zone diameters of 6 mm or less were classified as ineffective as this was the diameter of the test discs.

 

Analysis

The medians of the inhibition zone diameters were calculated for each essential oil and for the controls and were shown as column diagrams.

Results

All of the tested essential oils and oil mixtures showed good to moderate antibacterial and antimycotic effects against the tested strains. Inhibition zones of 6 mm to 49 mm were obtained.

Among the pure oils the greatest inhibition zones were obtained for lemongrass oil (up to 49 mm) and thyme oil (up to over 30 mm) with reference to all the tested strains. Of the oil mixtures, KMPT showed the greatest inhibition zones with reference to staphylococcal and candida strains. In the tests with streptococci, obvious inhibition zones for KMPT and Salviathymol were an expression of their good antimicrobial activity.

Even the tested resistant strains, such as MRSA and Candida krusei, reacted sensitively to the essential oils and oil mixtures, as confirmed by the obvious inhibition zones.

The olive oil and liquid paraffin controls had no antibacterial or antimycotic activity in any case, as the tested problem strains were able to grow uninhibited.

Inhibition zones up to 7 mm were obtained with 70 % ethanol in this experimental design. An inhibitory effect on bacterial and candida growth was confirmed for povidone iodine and chlorhexidine, which resulted in inhibition zones 10 mm to 25 mm in diameter generally.

The medians of the diameters of the inhibition zones are shown in figures 2a to 2c.

 

Discussion

The origins of the use of essential oils among Australian Aborigines probably go back centuries [10].

Since the start of the 20th century, essential oils have been used in Australia as antiseptics by immigrants and many of them are now commercially available [11]. In earlier studies, the antimicrobial effects of tea tree oil against pathogenic oral bacteria and oropharyngeal candidiasis were already described [8, 16], though it did not gain broad acceptance as an antiseptic in Europe or America.

To investigate antimicrobial effectiveness with microbiological tests, the antimicrobial activity of different essential oils on several pathogenic micro-organisms was tested in this study. As a guide, strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus haemolyticus and Candida albicans were tested first. All of these strains are clinically relevant in oral and maxillofacial surgery and are often a cause of oral, odontogenic and cutaneous infections. Special attention was paid to the problem pathogens MRSA and Candida krusei, which were also tested. Because the common antibiotics of first choice are no longer effective against MRSA and last-resort reserve antibiotics often have to be used, this strain is becoming an increasing problem especially in intensive care patients and acute hospitals. Candida krusei is often resistant clinically to common antimycotic agents and is a problem particularly in immunosuppressed patients and transplant recipients [16, 20]. Since the common treatment regimens are increasingly exhausted, the effective essential oils might be a therapeutic option for local use. Some of the tested oils showed marked inhibition zones of up to 49 mm, e. g. in the case of lemongrass oil against Candida krusei. Lemongrass oil achieved an inhibition zone of over 30 mm against MRSA also. The controls such as chlorhexi-dine and povidone iodine achieved inhibition zone diameters of 10 mm to 25 mm. Direct comparison of the inhibition zone diameters of different substances is not entirely admissible in the agar diffusion test. However, the marked inhibition zone diameters with the essential oils are impressive evidence of their antimicrobial effectiveness.

For peri-implant infections, anaerobes (e. g. Porphyro-monas gingivalis) certainly play a weightier role than the cocci tested here. However, the methods for testing essential oils in an anaerobic milieu (highly negative redox potential) have not yet been standardized and validated. Thus, this study has a more orienting character. However, the effectiveness against staphylococci and streptococci is clear evidence of an antibacterial action. Activity against the leading strains that cause peri-implantitis would therefore be likely. Essential oils might thus be a potential option for the treatment of peri-implant infections. The literature also provides further evidence of the antimicrobial effectiveness of essential oils which would be relevant for implantology [2].

Terpenen-4-ol, linalool and alpha-terpineol have been described as active components, e. g. of tea tree oil [4, 5, 15, 18]. It has been shown that these substances, especially terpinen-4-ol, can destroy the bacterial cell wall and cause changes in the potassium concentration gradient [6]. Moreover, inhibition of glucose-dependent cell respiration has been demonstrated [6, 9]. This suggests that effectiveness against anaerobes of relevance in peri-implantitis might be achieved. Consequently, use of these oils in the local treatment of peri-implant infections might be considered in order to circumvent the problems of local antibiotic use with regard to the development of resistance.

Clinical and immunological studies also provide evidence that the essential oils have anti-inflammatory characteristics [17], which may be due in part to inhibition of production of inflammatory mediators by the monocytes [13, 24]. Anti-inflammatory effects would be of considerable benefit in the treatment of peri-implantitis since inhibition of inflammatory mediator secretion would also help to limit bone atrophy due to inflammation. Promotion of wound healing by essential oils has been described and might assist the ideal goal of restitutio ad integrum [24, 26]. This would give them a clear and clinically relevant advantage compared to classic antiseptics such as povidone iodine and chlorhexidine.

The pure oils were tested in undiluted or undissolved form. In pure form, essential oils can have an intense intrinsic odor and would be too viscous for use in a spray bottle. They are therefore frequently dissolved in alcohol in order to improve their characteristics, especially for use in aromatherapy. In general, citric oils such as lemongrass oil or lemon oil are highly acceptable to patients. Melaleuca-like oils such as tea tree oil or eucalyptus oil sometimes encounter rejection, as we discovered in odor tests with patients and nursing staff. The combination of several oils can have synergistic effects and can improve the overall odor considerably (results of these studies not shown).

The essential oils on sale in Germany often have ethanol or synthetic perfume added to increase evaporation and make them suitable for aromatherapy requirements. The three oil mixtures tested here were also dissolved in alcohol (max. 30 %). With our own KMPT mixture, the readier evaporation induced by the alcohol should promote the pleasant intrinsic odor of the oils, allowing them to be used as an antiseptic spray in wound treatment. This has been confirmed in clinical use [24].

A frequent criticism is that the added ethanol alone is the cause of the antimicrobial characteristics. That is why ethanol in the high concentration of 70 % was tested as a control, achieving inhibition zones of up to 7 mm. Since the pure oils without added alcohol and the oil mixtures containing much less added alcohol produced marked inhibition zones, the antimicrobial pharmacological effects can essentially be attributed to the substances in the oils themselves.

The possibility that the physical lipophilic characteristics of the oils might be the reason for the inhibition of bacterial growth can be ruled out since the lipophilic controls, olive oil and liquid paraffin, did not demonstrate an inhibition zone in any case.

A possible disadvantage is the bitter taste of some concentrated pure oils, though the individual assessment differs. In the literature there are reports of systemic toxicity [16]. There have been isolated reports of contact dermatitis, which can occur with excessive use of undiluted tea tree oil [7] or eucalyptus oil [23]. So far, we have not encountered this in our patients. The proportion of photo-oxidants, which are held responsible for allergizing through the formation of degradation products in the oils, has been reduced in the oils we use by the manufacturer through plant cultivation and the manufacturing process [12, 14]. The situation may be different with synthetic oils or aromatherapy oils and allergizing would be possible. In any case, allergies to classic antiseptics such as povidone iodine are well-known.

The pharmacological composition of natural products varies depending on their origin and conditions of manufacture. This means that different varieties of tea tree oil or eucalyptus oil can have different activities because of different concentrations of active substance. In further studies we found marked differences in antimicrobial effectiveness in the oils from different manufacturers and different countries of origin (results of these studies not shown). We then selected the most effective oils for our applications and mixture. Thus, the results presented here apply primarily for the substances used by us.

We are currently conducting further studies to optimize the form of application of the essential oils for the treatment of peri-implant infections. In initial clinical tests, we have already carried out pocket irrigation. Application in gel form, possibly providing prolonged adhesion to the implant surface, is our current aim.

 

Conclusion

The tested essential oils exhibit clear antimicrobial effects against staphylococci, streptococci and candida. In particular, the effect on multi-resistant strains should be stressed. The anti-inflammatory properties of essential oils represent an advantage compared to classic antiseptics such as povidone iodine and chlorhexidine. The tested oils are produced naturally and cheaply. If the suspected antimicrobial effects against the dominant strains in peri-implant infections can be confirmed, essential oils may offer an alternative in the local treatment of these infections. This indication will be investigated in further studies.

Acknowledgments

This study is part of a series conducted in collaboration with Prof. Eugene Sherry, Faculty of Health Sciences and Medicine, Bond University, QLD, AUS, Dr. Sureshan Sivananthan, Dept. of Orthopaedic Surgery, University College of London, UK, and Dr. Paul AJ Russo, Dept. of Immunology, Australian National University, Canberra, AUS. We acknowledge the research grant from the Medical Faculty of Christian Albrecht University in Kiel.

Korrespondenzadresse:

Privatdozent Dr. Dr. Patrick H. Warnke

Klinik für Mund-, Kiefer- und Gesichtschirurgie

Christian-Albrechts-Universität zu Kiel

Arnold-Heller-Str. 16

24105 Kiel

E-Mail: warnke@mkg.uni-kiel.de

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Footnote

1 Department of Oral and Maxillofacial Surgery, University of Kiel, Germany

2 Faculty of Health Sciences and Medicine, Bond University, QLD, Gold Coast, Australia

3 Institute of Infection Medicine, University of Kiel, Germany

Übersetzung: LinguaDent

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