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In vitro and in vivo activity of tea tree oil against azole-susceptible and -resistant human pathogenic yeasts.

A tea tree oil (TTO) preparation of defined chemical composition was studied, using a microbroth method, for its in vitro activity against 115 isolates of Candida albicans, other Candida species and Cryptococcus neoformans. The fungal strains were from HIV-seropositive subjects, or from an established type collection, including reference and quality control strains. Fourteen strains of C. albicans resistant to fluconazole and/or itraconazole were also assessed. The same preparation was also tested in an experimental vaginal infection using fluconazole-itraconazole-susceptible or -resistant strains of C. albicans. TTO was shown to be active in vitro against all tested strains, with MICs ranging from 0.03% (for C. neoformans) to 0.25% (for some strains of C. albicans and other Candida species). Fluconazole- and/or itraconazole-resistant C. albicans isolates had TTO MIC50s and MIC90s of 0.25% and 0.5%, respectively. TTO was highly efficacious in accelerating C. albicans clearance from experimentally infected rat vagina. Three post-challenge doses of TTO (5%) brought about resolution of infection regardless of whether the infecting C. albicans strain was susceptible or resistant to fluconazole. Overall, the use of a reliable animal model of infection has confirmed and extended our data on the therapeutic effectiveness of TTO against fungi, in particular against C. albicans.

Animals↗

In vivo activity of terpinen-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-susceptible and -resistant human pathogenic Candida species.

BACKGROUND: Recent investigations on the antifungal properties of essential oil of Melaleuca alternifolia Cheel (Tea Tree Oil, TTO) have been performed with reference to the treatment of vaginal candidiasis. However, there is a lack of in vivo data supporting in vitro results, especially regarding the antifungal properties of TTO constituents. Thus, the aim of our study was to investigate the in vitro and the in vivo anti-Candida activity of two critical bioactive constituents of TTO, terpinen-4-ol and 1,8-cineole. METHODS: Oophorectomized, pseudoestrus rats under estrogen treatment were used for experimental vaginal infection with azole (fluconazole, itraconazole) -susceptible or -resistant strains of C. albicans. All these strains were preliminarily tested for in vitro susceptibility to TTO, terpinen-4-ol and 1,8-cineole for their antifungal properties, using a modification of the CLSI (formerly NCCLS) reference M27-A2 broth micro-dilution method. RESULTS: In vitro minimal inhibitory concentrations (MIC90) values were 0.06% (volume/volume) for terpinen-4-ol and 4% (volume/volume) for 1,8-cineole, regardless of susceptibility or resistance of the strains to fluconazole and itraconazole. Fungicidal concentrations of terpinen-4-ol were equivalent to the candidastatic activity. In the rat vaginal infection model, terpinen-4-ol was as active as TTO in accelerating clearance from the vagina of all Candida strains examined. CONCLUSION: Our data suggest that terpinen-4-ol is a likely mediator of the in vitro and in vivo activity of TTO. This is the first in vivo demonstration that terpinen-4-ol could control C. albicans vaginal infections. The purified compound holds promise for the treatment of vaginal candidiasis, and particularly the azole-resistant forms.

Animals↗

Leakage of K+ ions from Staphylococcus aureus in response to tea tree oil.

The leakage of K(+) ions from Staphylococcus aureus in response to tea tree oil (TTO) was investigated with an ion-selective electrode. The amount of leaked K(+) ions and the rate of leakage of K(+) ions induced by TTO were dependent on the concentration of TTO. Measurements of initial rates required less time than measurements of total amounts and provided an index of the interaction between TTO and the cell membrane. Thus, the initial rate of leakage might be a more useful measure of the antibacterial activity of TTO than the total amount.

Anti-Infective Agents, Local↗

Susceptibility to Melaleuca alternifolia (tea tree) oil of yeasts isolated from the mouths of patients with advanced cancer.

Yeasts that are resistant to azole antifungal drugs are increasingly isolated from the mouths of cancer patients suffering from oral fungal infections. Tea tree oil is an agent possessing antimicrobial properties that may prove useful in the prevention and management of infections caused by these organisms. In this study, 301 yeasts isolated from the mouths of 199 patients suffering from advanced cancer were examined by an in vitro agar dilution assay for susceptibility to tea tree oil. All of the isolates tested were susceptible, including 41 that were known to be resistant to both fluconazole and itraconazole. Clinical studies of tea tree oil as an agent for the prevention and treatment of oral fungal infections in immunocompromised patients merit consideration.

Anti-Infective Agents, Local↗

Tea tree oil: cutaneous effects of the extracted oil of Melaleuca alternifolia.

The use of botanical extracts for their perceived therapeutic benefits has gained increased popularity in this country and abroad. In particular, tea tree oil (the extracted oil of Melaleuca alternifolia) has gained widespread use for its purported antimicrobial and therapeutic effects. In parallel with this increased use is an expanding series of reported adverse effects, including allergic contact dermatitis, systemic contact dermatitis, linear immunoglobulin A disease, erythema multiforme-like id reactions, and systemic hypersensitivity reactions. We present a review of tea tree oil with regard to its history, chemistry, purported medicinal uses, and possible adverse cutaneous effects.

Allergens↗

Acaricidal activity of Melaleuca alternifolia (tea tree) oil: in vitro sensitivity of sarcoptes scabiei var hominis to terpinen-4-ol.

OBJECTIVE: To compare the acaricidal activity of Melaleuca alternifolia (tea tree) oil (TTO) and some of its individual active components on the itch mite Sarcoptes scabiei var hominis. DESIGN: In vitro acaricide sensitivity assessment. SETTING: The Menzies School of Health Research laboratory, located near the Infectious Diseases Ward of the Royal Darwin Hospital, Australia, where patients are admitted and treated for crusted scabies. PARTICIPANTS: Scabies mites (S scabiei var hominis) were collected from a 20-year-old Aboriginal woman admitted to the Royal Darwin Hospital with crusted scabies. Interventions Within 3 hours of collection, scabies mites were placed in continuous direct contact with the TTO products and control acaricides and were observed at regular intervals. MAIN OUTCOME MEASURES: Percentage of mites dead at regular observation intervals between 5 minutes and 24 hours during continuous exposure to the TTO products and acaricides. RESULTS: The 5% TTO and active component terpinen-4-ol were highly effective in reducing mite survival times. Statistically significant differences in mite survival curves were observed for 5% TTO, 2.1% terpinen-4-ol, 5% permethrin, and ivermectin (100 microg/g of Emulsifying Ointment British Pharmacopoeia 88). In vivo effectiveness was also observed. CONCLUSIONS: Documentation of resistance against antiectoparasitic compounds is increasing. Reported S scabiei treatment failures with lindane, crotamiton, and benzyl benzoate, as well as likely emerging resistance to 5% permethrin and oral ivermectin, are of concern and advocate for the identification and development of novel acaricidal drugs. Tea tree oil is a membrane-active biocide extracted from the tree M alternifolia. It is a principal antimicrobial in a wide range of pharmaceuticals sold in Australia, with the main active component being oxygenated terpenoids. The results suggest that TTO has a potential role as a new topical acaricide and confirm terpinen-4-ol as the primary active component.

Adult↗

In vitro activities of ketoconazole, econazole, miconazole, and Melaleuca alternifolia (tea tree) oil against Malassezia species.

The in vitro activities of ketoconazole, econazole, miconazole, and tea tree oil against 54 Malassezia isolates were determined by agar and broth dilution methods. Ketoconazole was more active than both econazole and miconazole, which showed very similar activities. M. furfur was the least susceptible species. M. sympodialis, M. slooffiae, M. globosa, and M. obtusa showed similar susceptibilities to the four agents.

Antifungal Agents↗

Reduction of nickel-induced contact hypersensitivity reactions by topical tea tree oil in humans.

OBJECTIVE AND DESIGN: Whilst the anti-microbial properties of tea tree oil (TTO) are established, the anti-inflammatory effects of TTO in human skin remain largely anecdotal and require evaluation. This study examined the effect of topically applied TTO on nickel-induced contact hypersensitivity reactions in human dorsal skin. TREATMENT: TTO (100%), a 5% TTO lotion, a placebo lotion (no TTO), or 100% macadamia oil were applied at days 3 and 5 after nickel exposure. METHODS: The flare area and erythema index were measured on days 3, 5 and 7. The regulatory effects of TTO were also investigated on the proliferative response to nickel or polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive and control subjects. RESULTS: TTO (100%) significantly reduced the flare area and erythema index when compared to the nickel-only sites. With respect to the erythema index, the anti-inflammatory effects were predominantly, but not exclusively, seen in a subgroup of nickel-sensitive subjects with a prolonged development phase of nickel-induced contact hypersensitivity response. The 5% TTO lotion, the placebo lotion and the 100% macadamia oil were all without significant effect. TTO significantly inhibited proliferation to nickel but not to non-specific polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive subjects. CONCLUSIONS: Topical application of 100% TTO may have therapeutic benefit in nickel-induced contact hypersensitivity in human skin. The mode of action of TTO requires further investigation, but may be an effect on the antigen presenting cells or the antigen presenting process in nickel-induced contact hypersensitivity, as well as vascular changes associated with this response.

Administration, Topical↗

A comparative study of the in vitro antimicrobial activity of tea tree oils s.l. with special reference to the activity of beta-triketones.

The in vitro antibacterial and antifungal activities of Australian tea tree oil, cajuput oil, niaouli oil, kanuka oil and manuka oil as well as of a beta-triketone complex isolated from manuka oil were investigated in a constituent-oriented study. The compositions of the oils were analysed by capillary GLC and GLC-MS. The MICs for sixteen different microorganisms were determined applying the broth dilution method. Australian tea tree oil showed the best overall antimicrobial effect. The best inhibitory effects on Gram-positive bacteria and dermatophytes were achieved with manuka oil due to its beta-triketone content.

Anti-Bacterial Agents↗

Comparative study on the in vitro antibacterial activity of Australian tea tree oil, cajuput oil, niaouli oil, manuka oil, kanuka oil, and eucalyptus oil.

To compare the antibacterial activity of the Australian tea tree oil (TTO) with various other medicinally and commercially important essential myrtaceous oils (cajuput oil, niaouli oil, kanuka oil, manuka oil, and eucalyptus oil) the essential oils were first analysed by GC-MS and then tested against various bacteria using a broth microdilution method. The highest activity was obtained by TTO, with MIC values of 0.25% for Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella choleraesuis, Shigella flexneri, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, S. saprophyticus, and S. xylosus. It is noteworthy that manuka oil exhibited a higher activity than TTO against gram-positive bacteria, with MIC values of 0.12%. Both TTO and manuka oil also demonstrated a very good antimicrobial efficacy against various antibiotic-resistant Staphylococcus species. Pseudomonas aeruginosa was resistant to all essential oils tested, even at the highest concentration of 4%.

Anti-Bacterial Agents↗

Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties.

Complementary and alternative medicines such as tea tree (melaleuca) oil have become increasingly popular in recent decades. This essential oil has been used for almost 100 years in Australia but is now available worldwide both as neat oil and as an active component in an array of products. The primary uses of tea tree oil have historically capitalized on the antiseptic and anti-inflammatory actions of the oil. This review summarizes recent developments in our understanding of the antimicrobial and anti-inflammatory activities of the oil and its components, as well as clinical efficacy. Specific mechanisms of antimicrobial and anti-inflammatory action are reviewed, and the toxicity of the oil is briefly discussed.

Bacteria↗

Assessment of the antibacterial activity of tea tree oil using the European EN 1276 and EN 12054 standard suspension tests.

The activity of tea tree oil (TTO) and TTO-containing products was investigated according to the EN 1276 and EN 12054 European suspension methods. The activity of different concentrations of TTO, a hygienic skin wash (HSW), an alcoholic hygienic skin wash (AHSW) and an alcoholic hand rub (AHR) was investigated. These formulations were assessed in perfect conditions with the EN 12054 test, and in perfect conditions as well as in the presence of interfering substances with the EN 1276 test, against Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa. With the latter test, the activity of the same formulations without TTO was also assessed as a control. With the EN 1276 test, the AHR achieved a >10(5)-fold reduction against all four test organisms within a 1-min contact time. The AHSW achieved a >or=10(5)-fold reduction against A. baumannii after a 1-min contact time and against S. aureus, E. coli and P. aeruginosa after a 5-min contact time. The efficacy of TTO appeared to be dependent on the formulation and the concentration tested, the concentration of interfering substances and, lastly, the organism tested. Nevertheless, 5% TTO achieved a >10(4)-fold reduction in P. aeruginosa cell numbers after a 5-min contact time in perfect conditions. TTO (5%) in 0.001% Tween 80 was significantly more active against E. coli and P. aeruginosa than against S. aureus and A. baumannii. With the EN 12054 test, after a 1-min contact time, 5% TTO in 0.001% Tween 80 and the AHSW achieved a >10(4)-fold reduction in E. coli and A. baumannii cell numbers, respectively, and the AHR achieved a >4 log10 reduction against all organisms tested. The formulations used in this study are now being tested using a novel ex vivo method as well as the in vivo European standard handwashing method EN 1499.

Acinetobacter baumannii↗

The bacterial multiple antibiotic resistant (Mar) phenotype leads to increased tolerance to tea tree oil.

Mutants of Escherichia coil strain AG100 exhibiting the multiple antibiotic resistance (Mar) phenotype demonstrated a greater level of tolerance to tea tree oil (TTO) compared with the parent strain. The ability of TTO to kill all E. coil strains studied was greater at 37 than at 30 degrees C. Growth of parent strain AG100 in the presence of salicylate, which induces the mar operon leading to the Mar phenotype, also increased tolerance to TTO. Escherichia coli Mar mutant YL1 demonstrated greater tolerance to antimicrobial terpenes found in TTO and did not leak K+ as rapidly in the presence of TTO when compared with its parent strain AG100. Attempts to isolate Mar mutants of Staphylococcus aureus using tetracycline gradients proved unsuccessful. However, when grown in the presence of salicylate, S. aureus strain BB255 demonstrated greater tolerance to TTO and did not leak K+ as rapidly in the presence of TTO compared with this strain grown without additions. This evidence demonstrates that bacterial Mar phenotypes increase tolerance to the killing action of TTO. This work also adds indirect evidence that the target of TTO is the cell membrane.

Anti-Infective Agents, Local↗

Treatment of prostatic abscesses by aspiration of the purulent matter and injection of tea tree oil into the cavities in dogs.

Ultrasonography-guided transabdominal needle aspiration was carried out to remove 3 to 14 ml of purulent matter from the cavities of prostatic abscesses in 6 dogs, and the same volume of tea tree oil was injected into the cavities to treat the abscesses. The same treatment was repeated 3 weeks later in 4 dogs, and subsequent disappearance of the purulent matter in the cavities and a marked reduction in the volume of the cavities were observed. These findings indicate that the treatment of prostatic abscesses by aspiration of the purulent matter and injection of tea tree oil into the cavities is very effective in dogs.

Abscess↗

Comparison of the effects in vitro of tea tree oil and plaunotol on methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus.

The effects in vitro of tea tree oil (TTO) and plaunotol were examined by monitoring the growth of a standard strain of Staphylococcus aureus FDA 209P and of fourteen methicillin-susceptible strains of S. aureus (MSSA), together with twenty methicillin-resistant strains (MRSA). The minimum inhibitory concentrations (MIC) and the doses for 50% inhibition of growth (ID50) were determined by the micro-broth dilution (MD) method, and the broth dilution with shaking (BDS) method, respectively. The MIC of plaunotol for 50 and 90% of the MSSA and MRSA were assessed by the MD method, as 16 microg/ml and > or = 1,024 microg/ml, respectively. No antibacterial effects of TTO on MSSA and MRSA were detected by the MD method. The growth-inhibitory effects of TTO on S. aureus by the BDS method were examined, and it appeared that TTO was effective over a lower range of concentrations than previously reported. It seems that TTO is very effective in vitro against MSSA and MRSA at high concentrations but less effective below 40 microg/ml of TTO.

Anti-Bacterial Agents↗

Tea tree oil reduces histamine-induced oedema in murine ears.

OBJECTIVE: To examine the effect of topically applied tea tree oil (TTO) on histamine-induced oedema in the ears of mice. METHODS AND RESULTS: For BALB/c mice, 10 microl undiluted TTO applied immediately after, but not 30 min before intradermal injection of 600 microg histamine in 10 microl, significantly suppressed oedema development. TTO applied after histamine injection also suppressed histamine-induced oedema in C57/BL6 mice. TTO applied immediately after intradermal injection of compound 48/80 (200 microg in 10 microl saline) also significantly reduced ear swelling. TTO suppressed histamine-induced oedema to the same extent in capsaicin-treated (neuropeptide-depleted) and control mice which suggests that TTO does not inhibit histamine-induced oedema by regulating the activity of peripheral sensory neurons. Terpinen-4-ol, the major water-soluble component of TTO, was equivalent in potency to TTO in the suppression of histamine-induced ear swelling. CONCLUSION: Topical application of TTO, and in particular terpinen-4-ol, may be effective in controlling histamine-induced oedema often associated with Type I allergic immediate hypersensitivities.

Administration, Topical↗

In vitro activity of Melaleuca alternifolia (tea tree) oil against bacterial and Candida spp. isolates from clinical specimens.

This study investigates the in vitro activity of tea tree oil (TTO) against a range of wild strains of microorganisms isolated from clinical specimens of leg ulcers and pressure sores. The antimicrobial effectiveness of TTO is determined in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC). The isolates include methicillin-resistant Staphylococcus aureus (MRSA), S. aureus, faecal streptococci, beta-haemolytic streptococci, coagulase-negative staphylococci, Pseudomonas spp. and coliform bacilli. Eleven Candida spp. isolates from skin and vaginal swabs also are tested. Using an agar dilution assay, the MICs of TTO in 88 out of 90 isolates was 0.5-1.0% (v/v), whilst with P. aeruginosa it was >2% (v/v). A broth microdilution method was used to determine MIC and minimum cidal concentration (MCC) of 80 isolates. In 64 isolates, TTO produced an inhibitory and cidal effect at 3% and 4% (v/v), respectively. S. aureus and Candida spp. were the most susceptible to TTO, with MICs and MBCs of 0.5% and 1%, respectively. P. aeruginosa and the faecal streptococci isolates, with MICs and MBCs of >8%, were resistant to TTO.

Anti-Infective Agents, Local↗