Commercial Essential Oils as Potential Antimicrobials to Treat Skin Diseases

Abstract

Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman’s literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils.

1. Introduction

The skin is the body’s largest mechanical barrier against the external environment and invasion by microorganisms. It is responsible for numerous functions such as heat regulation and protecting the underlying organs and tissue [1, 2]. The uppermost epidermal layer is covered by a protective keratinous surface which allows for the removal of microorganisms via sloughing off of keratinocytes and acidic sebaceous secretions. This produces a hostile environment for microorganisms. In addition to these defences, the skin also consists of natural microflora which offers additional protection by competitively inhibiting pathogenic bacterial growth by competing for nutrients and attachment sites and by producing metabolic products that inhibit microbial growth. The skin’s natural microflora includes species of Corynebacterium, staphylococci, streptococci, Brevibacterium, and Candida as well as Propionibacterium [3–8].

In the event of skin trauma from injuries such as burns, skin thinning, ulcers, scratches, skin defects, trauma, or wounds, the skin’s defence may be compromised, allowing for microbial invasion of the epidermis resulting in anything from mild to serious infections of the skin. Common skin infections caused by microorganisms include carbuncles, furuncles, cellulitis, impetigo, boils (Staphylococcus aureus), folliculitis (S. aureus, Pseudomonas aeruginosa), ringworm (Microsporum spp., Epidermophyton spp., and Trichophyton spp.), acne (P. acnes), and foot odour (Brevibacterium spp.) [3, 8–11]. Environmental exposure, for example, in hospitals where nosocomial infections are prominent and invasive procedures make the patient vulnerable, may also create an opportunity for microbial infection. For example, with the addition of intensive therapy and intravascular cannulae, S. epidermidis can enter the cannula and behave as a pathogen causing bloodborne infections. Noninfective skin diseases such as eczema can also result in pathogenic infections by damaging the skin, thus increasing the risk of secondary infection by herpes simplex virus and/or S. aureus [5, 8, 12].

Skin infections constitute one of the five most common reasons for people to seek medical intervention and are considered the most frequently encountered of all infections. At least six million people worldwide are affected by chronic wounds and up to 17% of clinical visits are a result of bacterial skin infections and these wounds are a frequent diagnosis for hospitalised patients. These are experienced daily and every doctor will probably diagnose at least one case per patient. Furthermore, skin diseases are a major cause of death and morbidity [8, 13, 14]. The healing rate of chronic wounds is affected by bacterial infections (such as S. aureus, E. coli, and P. aeruginosa), pain, inflammation, and blood flow, and thus infection and inflammation control may assist in accelerating healing [15–17].

Topical skin infections typically require topical treatment; however, due to the ability of microbes to evolve and due to the overuse and incorrect prescribing of the current available conventional antimicrobials, there has been emergence of resistance in common skin pathogens such as S. aureus resulting as methicillin-resistant Staphylococcus aureus (MRSA) and other such strains. Treatment has therefore become a challenge and is often not successful [8, 18, 19]. In some regions of the world, infections are unresponsive to all known antibiotics [20]. This threat has become so severe that simple ulcers now require treatment with systemic antibiotics [21]. A simple cut on the finger or a simple removal of an appendix could result in death by infection. The World Health Organization (WHO) has warned that common infections may be left without a cure as we are headed for a future without antibiotics [22]. Therefore, one of the solutions available is to make use of one of the oldest forms of medicine, natural products, to treat skin infections and wounds [18, 23].

Complementary and alternative medicines (CAMs) are used by 60–80% of developing countries as they are one of the most prevalent sources of medicine worldwide [24–27]. Essential oils are also one of the most popular natural products, with one of their main applications being for their use in dermatology [28–30]. In fact, of all CAMs, essential oils are the most popular choice for treating fungal skin infections [13, 31]. Their use in dermatology, in the nursing profession, and in hospitals has been growing with great popularity worldwide, especially in the United States and the United Kingdom [1, 27, 32–35]. Furthermore, the aromatherapeutic literature [1, 2, 26, 32, 36–43] identifies numerous essential oils for dermatological use, the majority of which are recommended for infections. This brought forth the question as to the efficacy of commercial essential oils against the pathogens responsible for infections. The aim of this review was to collect and summarise the in vivo, in vitro, and clinical findings of commercial essential oils that have been tested against infectious skin diseases and their pathogens and, in doing so, offer aromatherapists and dermatologists valuable information regarding the effectiveness of essential oils for dermatological infections.

The readily available aromatherapeutic literature has reported over 90 (Table 1) commercial essential oils that may be used for treating dermatological conditions [1, 2, 26, 32, 36–43]. An overview of the skin related uses can be seen in Figure 1. Essential oils are mostly used for the treatment of infections caused by bacteria, fungi, or viruses (total 62%). This is followed by inflammatory skin conditions (20%) such as dermatitis, eczema, and lupus and then general skin maintenance (18%) such as wrinkles, scars, and scabs, which are the third most common use of essential oils. Other applications include anti-inflammatory and wound healing applications (Figure 1). Of the 98 essential oils recommended for dermatological use, 88 are endorsed for treating skin infections. Of these, 73 are used for bacterial infections, 49 specifically for acne, 34 for fungal infections, and 16 for viral infections.

Figure 1 

Summary of categorised dermatological conditions in which essential oils are used.

2. Materials and Methods

2.1. Searching Strategy/Selection of Papers

The aim of the comparative review was to identify the acclaimed dermatological commercial essential oils according to the aromatherapeutic literature and then compare and analyse the available published literature. This will serve as a guideline in selecting appropriate essential oils in treating dermatological infections. The analysed papers were selected from three different electronic databases: PubMed, ScienceDirect, and Scopus, accessed during the period 2014–2016. The filters used included either “essential oils”, “volatile oils”, or “aromatherapy” or the scientific or common name for each individual essential oil listed in Table 1 and the additional filters “antimicrobial”, “antibacterial”, “skin”, “infection”, “dermatology”, “acne”, “combinations”, “fungal infections”, “dermatophytes”, “Brevibacteria”, “odour”, “antiviral”, “wounds”, “dermatitis”, “allergy”, “toxicity”, “sentitisation”, or “phototoxicity”.

2.2. Inclusion Criteria

In order to effectively understand the possible implications and potential of essential oils, the inclusion criteria were broad, especially with this being the first review to collate this amount of scientific evidence with the aromatherapeutic literature. Inclusion criteria included the following:(i)Type of in vitro studies for bacterial and fungal pathogens by means of the microdilution assay, macrodilution assay, or the agar dilution assay(ii)In vivo studies(iii)Antiviral studies(iv)Case reports(v)Animal studies(vi)All clinical trials

2.3. Exclusion Criteria

Papers or pieces of information were excluded for the following reasons:(i)Lack of accessibility to the publication(ii)If the incorrect in vitro technique (diffusion assays) was employed(iii)Indigenous essential oils with no relevance to commercial oils(iv)If they were in a language not understood by the authors of the review(v)Pathogens studied not relevant to skin disease

2.4. Data Analysis

The two authors (Ané Orchard and Sandy van Vuuren) conducted their own data extraction independently, after which critical analysis was applied. Information was extrapolated and recorded and comments were made. Observations were made and new recommendations were made as to future studies.

3. Results

3.1. Description of Studies

After the initial database search, 1113 reports were screened. Duplicates were removed, which brought the article count down to 513, after which the abstracts were then read and additional reports removed based on not meeting the inclusion criteria. A final number of 349 articles were read and reviewed. Of these, 143 were in vitro bacterial and fungal studies (individual oil and 45 combinations), two in vivo studies, 15 antiviral studies, 19 clinical trials, and 32 toxicity studies. The process that was followed is summarised in Figure 2.

Figure 2 

Flow diagram of the review approach.

3.2. Experimental Approaches

3.2.1. Chemical Analysis

Essential oils are complex organic (carbon containing) chemical entities, which are generally made up of hundreds of organic chemical compounds in combination that are responsible for the essential oil’s many characteristic properties. These characteristics may include medicinal properties, such as anti-inflammatory, healing, or antimicrobial activities, but may also be responsible for negative qualities such as photosensitivity and toxicity [37].

Even with the high quality grade that is strived for in the commercial sector of essential oil production, it must be noted that it is still possible for essential oil quality to display discrepancies, changes in composition, or degradation. The essential oil composition may even vary between the same species [1, 44]. This may be due to a host of different factors such as the environment or location that the plants are grown in, the harvest season, which part of the plant was used, the process of extracting the essential oil, light or oxygen exposure, the storage of the oil, and the temperature the oil was exposed to [45–51].

Gas chromatography in combination with mass spectrometry (GCMS) is the preferred technique for analysis of essential oils [52]. This is a qualitative and quantitative chemical analysis method which allows for the assurance of the essential oil quality through the identification of individual compounds that make up an essential oil [1, 45, 53]. It has clearly been demonstrated that there is a strong correlation between the chemical composition and antimicrobial activity [51, 54, 55]. Understanding the chemistry of essential oils is essential for monitoring essential oil composition, which then further allows for a better understanding of the biological properties of essential oils. It is recommended to always include the chemical composition in antimicrobial studies [56].

3.3. Antimicrobial Investigations

Several methods exist that may be employed for antimicrobial analysis, with two of the most popular methods being the diffusion and the dilution methods [56–59].

3.3.1. Diffusion Method

There are two types of diffusion assays. Due to the ease of application, the disc diffusion method is one of the most commonly used methods [60]. This is done by applying a known concentration of essential oil onto a sterile filter paper disc. This is then placed onto agar which has previously been inoculated with the microorganism to be tested, or it is spread on the surface. If necessary, the essential oil may also be dissolved in an appropriate solvent. The other diffusion method is the agar diffusion method, where, instead of discs being placed, wells are made in the agar into which the essential oil is instilled. After incubation, antimicrobial activity is then interpreted from the zone of inhibition (measured in millimetres) using the following criteria: weak activity (inhibition zone ≤ 12 mm), moderate activity (12 mm < inhibition zone < 20 mm), and strong activity (inhibition zone ≤ 20 mm) [24, 60–62].

Although this used to be a popular method, it is more suitable to antibiotics rather than essential oils as it does not account for the volatile nature of the essential oils. Essential oils also diffuse poorly through an aqueous medium as they are hydrophobic. Thus, the results are less reliable as they are influenced by the ability of the essential oil to diffuse through the agar medium, resulting in variable results, false negatives, or a reduction in antimicrobial activity [24, 63]. The results have been found to vary significantly when tested this way and are also influenced by other factors such as disc size, amount of compound applied to the disc, type of agar, and the volume of agar [57, 59, 64–68]. It has thus been recommended that results are only considered where the minimum inhibitory concentration (MIC) or cidal concentration values have been established [65].

3.3.2. Dilution Methods

The dilution assays are reliable, widely accepted, and promising methods for determining an organism’s susceptibility to inhibitors. The microdilution method is considered the “gold standard” [64, 68–70]. This is a quantitative method that makes it possible to calculate the MIC and allows one to understand the potency of the essential oil [68, 71]. With one of the most problematic characteristics of essential oils being their volatility, the microdilution technique allows for an opportunity to work around this problem as it allows for less evaporation due to the essential oil being mixed into the broth [67].

This microdilution method makes use of a 96-well microtitre plate under aseptic conditions where the essential oils (diluted in a solvent to a known concentration) are serially diluted. Results are usually read visually with the aid of an indicator dye. The microdilution results can also be interpreted by reading the optical density [72, 73]; however, the shortcoming of this method is that the coloured nature of some oils may interfere with accurate turbidimetric readings [74].

Activity is often classified differently according to the quantitative method followed. van Vuuren [56] recommended 2.00 mg/mL and less for essential oils to be considered as noteworthy, Agarwal et al. [75] regarded 1.00% and less, and Hadad et al. [76] recommended ≤250.00 μg/mL. On considering the collection of data and frequency of certain MIC values, this review recommends MIC values of ≤1.00 mg/mL as noteworthy.

The macrodilution method employs a similar method to that of the microdilution method, except that, instead of a 96-well microtitre plate being used, multiple individual test tubes are used. Although the results are still comparable, this is a time-consuming and a tedious method, whereas the 96-well microtitre plate allows for multiple samples to be tested per plate, allowing for speed, and it makes use of smaller volumes which adds to the ease of its application [77, 78]. The agar dilution method is where the essential oil is serially diluted, using a solvent, into a known amount of sterile molten agar in bottles or tubes and mixed with the aid of a solvent. The inoculum is then added and then the agar is poured into plates for each dilution and then incubated. The absence of growth after incubation is taken as the MIC [79–81].

3.3.3. The Time-Kill Method

The time-kill (or death kinetic) method is a labour intensive assay used to determine the relationship between the concentration of the antimicrobial and the bactericidal activity [82]. It allows for the presentation of a direct relationship in exposure of the pathogen to the antimicrobial and allows for the monitoring of a cidal effect over time [74]. The selected pathogen is exposed to the antimicrobial agent at selected time intervals and aliquots are then sampled and serially diluted. These dilutions are then plated out onto agar and incubated at the required incubation conditions for the pathogen. After incubation, the colony forming units (CFU) are counted. These results are interpreted from a logarithmic plot of the amount of remaining viable cells against time [74, 82, 83]. This is a time-consuming method; however, it is very useful for deriving real-time exposure data.

3.4. Summary of Methods

The variation in essential oil test methods makes it difficult to directly compare results [24, 58]. Numerous studies were found to employ the use of a diffusion method due to its acclaimed “ease” and “time saving” ability of the application. Researchers tend to use this as a screening tool whereby results displaying interesting outcomes are further tested using the microdilution method [84–87]. The shortcoming of this method is that firstly, due to the discussed factors affecting the diffusion methods, certain essential oils demonstrate no inhibition against the pathogen, and thus further studies with the oils are overlooked. Secondly, the active oils are then investigated further using the microdilution method. Therefore, the researchers have now doubled the amount of time required to interpret the quantitative data. Thirdly, the method may be believed to be a faster method if one considers the application; however, if one considers the preparation of the agar plates and their risk of contamination as well as the overall process of this method, there is very little saving of time and effort.

It is recommended to follow the correct guidelines as set out by the Clinical and Laboratory Standards Institute M38-A (CLSI) protocol [88] and the standard method proposed by the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing (AFST-EUCAST) [89] for testing with bacteria and filamentous fungi.

Other factors that may affect results and thus make it difficult to compare published pharmacological results of essential oils are where data is not given on the chemical composition, the microbial strain number, temperature and length of incubation, inoculum size, and the solvent used. The use of appropriate solvents helps address the factor of poor solubility of essential oils. Examples include Tween, acetone, dimethylformamide (DMF), dimethylsulfoxide (DMSO), and ethanol. Tween, ethanol, and DMSO have, however, been shown to enhance antimicrobial activity of essential oils [24, 53, 90]. Soković et al. [91] tested antimicrobial activity with ethanol as the solvent and Tween. When the essential oils were diluted with Tween, it resulted in a greater antifungal activity; however, Tween itself does not display its own antimicrobial activity [92]. Eloff [93] identified acetone as the most favourable solvent for natural product antimicrobial studies.

The inoculum is a representative of the microorganisms present at the site of infection [94]. When comparing different articles, the bacterial inoculum load ranges from to  CFU/mL. The antibacterial activity is affected by inoculum size [62, 95–99]. If this concentration is too weak, the effect of the essential oils strengthens; however, this does not allow for a good representation of the essential oil’s activity. If the inoculum is too dense, the effect of the essential oil weakens and the inoculum becomes more prone to cross contamination [100]. Future studies should aim to keep the inoculum size at the recommended  CFU/mL [99].

4. Pathogenesis of Wounds and Skin Infections and the Use of Essential Oils

The pathogenesis of the different infections that are frequently encountered in wounds and skin infections is presented in Table 2. A more in-depth analysis of essential oils and their use against these dermatological pathogens follows.

4.1. Gram-Positive Bacteria

The Gram-positive bacterial cell wall is comprised of a 90–95% peptidoglycan layer that allows for easy penetration of lipophilic molecules into the cells. This thick lipophilic cell wall also results in essential oils making direct contact with the phospholipid bilayer of the cell membrane which allows for a physiological response to occur on the cell wall and in the cytoplasm [183, 184].

4.1.1. Staphylococcus aureus

Staphylococcus aureus is a common Gram-positive bacterium that can cause anything from local skin infections to fatal deep tissue infections. The pathogen is also found colonising acne and burn wounds [185–187]. Methicillin-resistant S. aureus (MRSA) is one of the most well-known and widespread “superbugs” and is resistant to numerous antibiotics [158]. Methicillin-resistant S. aureus strains can be found to colonise the skin and wounds of over 63%–90% of patients and have been especially infamous as being the dreaded scourge of hospitals for several years [22, 188–190]. Staphylococcus aureus has developed resistance against erythromycin, quinolones, mupirocin, tetracycline, and vancomycin [190–192].

Table 3 shows some of the antimicrobial in vitro studies undertaken on commercial essential oils and additional subtypes against this most notorious infectious agent of wounds. Of the 98 available commercial essential oils documented from the aromatherapeutic literature for use for dermatological infections, only 54 oils have been tested against S. aureus and even fewer against the resistant S. aureus strain. This is troubling, especially if one considers the regularity of S. aureus resistance. It should be recommended that resistant S. aureus strains always be included with every study.

When considering the antimicrobial activity of the tested essential oils, it can be noted how the main compounds influence overall antimicrobial activity. Melaleuca alternifolia (tea tree), rich in terpinen-4-ol, showed noteworthy activity, and Anthemis aciphylla var. discoidea (chamomile) containing α-pinene and terpinen-4-ol displayed noteworthy activity (1.00 mg/mL) [114], whereas the essential oil predominantly containing terpinen-4-ol displayed an MIC value of 0.50 mg/mL. The Origanum spp. (Origanum scabrum and Origanum vulgare) were shown to display rather impressive antimicrobial activity, which appeared to predominantly be related to the amount of carvacrol [163]. Geraniol also appears to be a compound that influences antimicrobial activity against the staphylococci spp. as can be seen for Backhousia citriodora (lemon myrtle) and Cymbopogon martinii (palmarosa) (geraniol 61.6%) [125, 126]. Cymbopogon martinii, with lower levels of geranial (44.80%), showed moderate antimicrobial activity [99]. Mentha piperita (peppermint) had higher antimicrobial activity for oils with higher concentrations of menthol [128, 155]. Laurus nobilis (bay), Styrax benzoin, and Cinnamomum zeylanicum (cinnamon), each rich in eugenol, were found to have notable activity [99].

It is interesting to consider the essential oils investigated and to compare them to what is recommended in the aromatherapeutic literature. For example, Lavandula angustifolia (lavender) is recommended for abscesses, carbuncles, and wounds [2, 26, 32, 36–43], which all involve S. aureus; however, in vitro activity was found to discount this oil as an antimicrobial [99, 136, 139, 140]. The same could be said about essential oils such as Achillea millefolium (yarrow) [112], Anthemis nobilis (Roman chamomile) [99], Boswellia carteri (frankincense) [116], Citrus aurantifolia (lime) [80], Foeniculum vulgare (fennel) [132, 133], and Melissa officinalis (lemon balm) [139].

Some clinical studies included the evaluation of the effects of essential oils on malodorous necrotic ulcers of cancer patients. The use of an essential oil combination (mostly containing Eucalyptus globulus (eucalyptus)) resulted in a decrease in inflammation, reduction of the odour, and improved healing rates [193]. Edwards-Jones et al. [194] performed a clinical study with a wound dressing containing essential oils to decrease infection risk. Ames [195] found Melaleuca alternifolia (tea tree) to be effective in treating wounds; and Matricaria recutita (German chamomile) with L. angustifolia at a 50 : 50 ratio diluted in calendula oil was found to improve leg ulcers and pressure sores.

Methicillin-resistant S. aureus hinders the rate of wound healing, which may lead to chronic wounds [196]. Delayed wound healing has been proven to lead to psychological stress and social isolation [197, 198]. A randomised controlled trial, consisting of 32 patients (16 in control group, 16 in placebo group) with stage II and above MRSA-colonised wounds that were not responding to treatment, was undertaken where the control group was treated with a 10% topical M. alternifolia preparation and was found to effectively decrease colonising MRSA in 87.5% of patients and result in a 100% healing rate within 28 days [196]. These studies lead to the high recommendation of the incorporation of this essential oil combination in palliative care.

Methicillin-resistant S. aureus may potentially be carried and propagated by hospital staff and patients, which is an acknowledged risk for hospital-acquired infections [147, 189]. Therefore, successful decolonisation of MRSA from patients and good hygiene may improve the microbial load, number of reinfections, and ultimately therapeutic outcomes of patients [199]. A topical preparation containing M. alternifolia essential oil has been considered for assistance in eradicating MRSA in hospitals, due to its reported efficacy [200]. The largest randomised trial against MRSA colonisation included 224 patients where the control group was treated with 2% nasal mupirocin applied three times a day, 4% chlorhexidine gluconate soap used at least once a day, and 1% silver sulfadiazine cream applied to skin infections once a day. The study group was treated with 10% M. alternifolia oil nasal cream applied three times a day and 5% M. alternifolia oil body wash used at least once daily with a 10% M. alternifolia cream applied to skin infections. The results showed that 41% of patients in the study group were cleared as opposed to 49% of patients on the standard therapy [200]. A small three-day pilot study was designed by Caelli et al. [189] to observe whether daily washing with a 5% M. alternifolia oil would clear MRSA colonisation which may result in ICU patient outcome improvement [199]. The test group made use of 4% M. alternifolia nasal ointment and 5% M. alternifolia oil body wash and was compared to a conventional treatment consisting of 2% mupirocin nasal ointment and triclosan body wash. The test group overall was found to have more improvement at the infection site when compared to the control group. Although the pilot study was too small to be statistically significant, the researchers did find that the M. alternifolia oil performed better than the conventional treatment and was effective, nontoxic, and well tolerated [189]. Messager et al. [90] tested 5% M. alternifolia ex vivo in a formulation, where it again was proven to decrease the pathogenic bacteria on the skin. In another study, M. alternifolia oil was investigated to determine the influence on healing rates [201]. The patients were treated with water-miscible tea tree oil (3.30%) solution applied as part of the wound cleansing regimen. This study used this oil as a wash only three times a week which is not how this oil is prescribed and hence the results were not positive. A more accurate method of study was shown by Chin and Cordell [202], where M. alternifolia oil was used in a dressing for wound healing abilities. All patients, except for one, were found to have an accelerated healing rate of abscessed wounds and cellulitis. The concluding evidence shows that there is definitely potential for the use of M. alternifolia (tea tree) oil as an additional/alternative treatment to standard wound treatments [203].

The healing potential of Commiphora guidotti (myrrh) was investigated via excisions of rats. The authors could confidently report on an increased rate in wound contraction and candid wound healing activity that was attributed to the antimicrobial and anti-inflammatory effects of this oil [204]. Ocimum gratissimum (basil) was also found by Orafidiya et al. [205] to promote wound healing by eradicating the infectious pathogens and by inducing early epithelialisation and moderate clotting formation, thereby accelerating scab formation, contraction, and granulation.

From these studies, clearly, M. alternifolia has shown great promise against S. aureus. However, considering the potential of essential oils in clinical practice and comparing them to essential oils with promising in vitro activity, other oils such as Cymbopogon citratus (lemongrass), Santalum album (sandalwood), and Vetiveria zizanioides/Andropogon muricatus (vetiver) should in the future be paid the same amount of attention.

4.1.2. Pathogens Involved in Acne

Pathogens associated with acne include Propionibacterium acnes, Propionibacterium granulosum, and Staphylococcus epidermidis [206–208]. Methicillin-resistant S. epidermidis (MRSE) have become extensively problematic microorganisms in the recent years due to their antimicrobial resistance and P. acnes has developed resistance to tetracycline, erythromycin, and clindamycin. Both have also shown multidrug resistance, including against quinolones [158, 188, 206]. Table 4 displays the in vitro antimicrobial efficacies of commercial essential oils against bacteria involved in the pathogenesis of acne. When observing the number of commercial essential oils that are recommended for acne treatment, less than half of the commercial oils have actually focused on S. epidermidis, P. granulosum, and P. acnes. Overall, the acne pathogens have been sorely neglected in essential oil studies.

For Anthemis aciphylla var. discoidea (chamomile) 0.13–0.25 mg/mL, initially, it appeared that higher α-pinene and lower terpinen-4-ol showed higher antimicrobial activity. However, the sample with terpinen-4-ol predominantly as its main component displayed the best activity at 0.06 mg/mL. This makes α-pinene appear as an antimicrobial antagonist. Cinnamomum zeylanicum, Rosa centifolia (rose), L. angustifolia, and Syzygium aromaticum (clove) displayed noteworthy antimicrobial activity against both S. epidermidis and P. acnes. Only the latter two are, however, recommended in the aromatherapeutic literature for the treatment of acne. Leptospermum scoparium (manuka) showed noteworthy activity for both P. acnes and S. epidermidis; however, Tween 80 was used as a solvent, which may overexaggerate the antimicrobial activity. Another study also found L. scoparium to effectively inhibit P. acnes. As was seen against S. aureus, O. scabrum and O. vulgare also notably inhibited S. epidermidis. Unfortunately, these oils were not studied against P. acnes. Cymbopogon citratus was shown to effectively inhibit P. acnes; however, no data was available against S. epidermidis. Essential oils such as S. album, V. zizanioides, Viola odorata (violet), Citrus aurantium var. amara (petitgrain), and Citrus bergamia (bergamot) are a few that are recommended for the treatment of acne and other microbial infections [2, 26, 32, 36, 37, 40–43] in the aromatherapeutic literature that are yet to be investigated.

Some clinical studies have shown promising results. A four-week trial comparing O. gratissimum oil with 10% benzoyl peroxide and a placebo was conducted and was aimed at reducing acne lesions in students. The 2% and 5% O. gratissimum oils in the hydrophilic cetomacrogol base were found to reduce acne lesions faster than standard therapy, and they were well tolerated. The 5% preparation, despite being highly effective, caused skin irritation. Overall, O. gratissimum oil showed excellent potential in the management of acne as it was as effective as benzoyl peroxide, although it was less popular with patients due to the unpleasant odour [217].

Melaleuca alternifolia oil demonstrated in vitro antimicrobial and anti-inflammatory activity against P. acnes and S. epidermidis and is in fact the essential oil on which most clinical trials have been undertaken. Bassett et al. [218] performed one of the first rigorous single-blinded randomised (RCT) controlled trials consisting of 124 patients that assessed the efficacy of 5% M. alternifolia gel in comparison to 5% benzoyl peroxide lotion in the management of mild to moderate acne. Both treatments showed equal improvement in the acne lesions. Enshaieh et al. [219] evaluated the efficacy of 5% M. alternifolia on mild to moderate acne vulgaris. The 5% M. alternifolia oil was found to be effective in improving the number of papules in both inflammatory and noninflammatory acne lesions and was found to be more effective than the placebo. Proven efficacy has made M. alternifolia preparations popular in acne products.

Other oil studies included a gel formulation containing acetic acid, Citrus sinensis (orange), and Ocimum basilicum (sweet basil) essential oils, which was tested in acne patients. The combination of these antimicrobial essential oils and the keratolytic agent resulted in a 75% improvement in the rate of acne lesion healing [220].

If one examines the results displayed in Table 4, essential oils such as Anthemis aciphylla var. discoidea (chamomile), C. zeylanicum, Citrus aurantium (bitter orange), O. vulgare (oregano), and S. aromaticum displayed higher antimicrobial activity in vitro than M. alternifolia, yet these essential oils have to be investigated clinically.

4.1.3. Gram-Negative Bacteria

The Gram-negative bacterial cell wall consists of a 2-3 nm thick peptidoglycan layer (thinner than Gram-positive bacteria), which means that the cell wall consists of a very small percentage of the bacteria. The cell wall is further surrounded by an outer membrane (OM) which is comprised of a double layer of phospholipids that are linked to an inner membrane by lipopolysaccharides (LPS). This OM protects the bacteria from lipophilic particles; however, it makes them more vulnerable to hydrophilic solutes due to the abundance of porin proteins that serve as hydrophilic transmembrane channels [184, 221, 222].

Gram-negative pathogens present a serious threat with regard to drug resistance, especially Escherichia coli and Pseudomonas aeruginosa [190, 192]. These pathogens that are found to colonise wounds often cause multidrug resistance [166, 223]. β-Lactamase-positive E. coli is appearing frequently among nonhospital patients [224]. Pseudomonas aeruginosa is a regular cause of opportunistic nosocomial infections [187]. It is often involved in localised skin infections, green nail syndrome, and interdigital infection, colonises burn wounds, and may expand into a life-threatening systemic illness [225].

A number of essential oils display antimicrobial activity against E. coli and P. aeruginosa with the predominant studies having been done against E. coli (Table 5). The Gram-negative pathogens appear to be a lot more resistant to essential oil inhibition than the Gram-positive bacteria, but this a known fact.