Antifungal activity of Lavandula angustifolia essential oil against Candida albicans yeast and mycelial form.

The antifungal activity of the essential oil of Lavandula angustifolia Mill. (lavender oil) and its main components, linalool and linalyl acetate, was investigated against 50 clinical isolates of Candida albicans (28 oropharyngeal strains, 22 vaginal strains) and C. albicans ATCC 3153. Growth inhibition, killing time and inhibition of germ tube formation were evaluated. The chemical composition of the essential oil was determined by gas chromatography and mass spectrometry. Lavender oil inhibited C. albicans growth: mean minimum inhibitory concentration (MIC) of 0.69% (vol./vol.) (vaginal strains) and 1.04% (oropharyngeal strains); mean MFC of 1.1% (vaginal strains) and 1.8% (oropharyngeal strains). Linalool was more effective than essential oil: mean MIC of 0.09% (vaginal strains) and 0.29% (oropharyngeal strains); mean MFC of 0.1% (vaginal strains) and 0.3% (oropharyngeal strains). Linalyl acetate was almost ineffective. Lavender oil (2%) killed 100% of the C. albicans ATCC 3153 cells within 15 min; linalool (0.5%) killed 100% of the cells within 30 s. The essential oil inhibited germ tube formation (mean MIC of 0.09%), as did the main components (MIC of 0.11% for linalool and 0.08% for linalyl acetate). Both the essential oil and its main components inhibited hyphal elongation of C. albicans ATCC 3153 (about 50% inhibition at 0.016% with each substance). Lavender oil shows both fungistatic and fungicidal activity against C. albicans strains. At lower concentrations, it inhibits germ tube formation and hyphal elongation, indicating that it is effective against C. albicans dimorphism and may thus reduce fungal progression and the spread of infection in host tissues.

Effect of propolis on virulence factors of Candida albicans.

Propolis is a resinous substance collected by honeybees from plant sources. Its antimicrobial activity has been well documented but little is specifically known about its activity on virulence factors of Candida albicans. The aim of this work was therefore to evaluate in vitro the propolis effect on yeast-mycelial conversion (Y-M), extracellular phospholipase activity and fungal adhesion to epithelial cells. The two propolis samples used significantly inhibited the C. albicans strains tested, showing a rapid (between 30 seconds and 15 minutes), dose-dependent cytocidal activity and an inhibitory effect on Y-M conversion at a concentration of 0.22 mg/ml. Moreover, the hyphal length was reduced even at lower propolis concentration. Propolis also caused a dose- and time-dependent inhibition of phospholipase activity. No clear effect was shown on adherence to buccal epithelial cells and surface structure hydrophobicity, but damage to the plasma membrane structure was demonstrated with the Propidium Iodide test.

In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi.

The antifungal activity of Melaleuca alternifolia Maiden (Myrtaceae) essential oil against yeasts (Candida spp., Schizosaccharomyces pombe, Debaryomyces hansenii) and dermatophytes (Microsporum spp. and Tricophyton spp.) is reported. We focused on the ability of tea tree oil to inhibit Candida albicans conversion from the yeast to the pathogenic mycelial form. Moreover we carried out broth microdilution test and contact tests to evaluate the killing time. M. alternifolia essential oil inhibited the conversion of C. albicans from yeast to the mycelial form at a concentration of 0.16% (v/v). The minimum inhibitory concentrations (MICs) ranged from 0.12% to 0.50% (v/v) for yeasts and 0.12% to 1% (v/v) for dermatophytes; the cytocidal activity was generally expressed at the same concentration. These results, if considered along with the lipophilic nature of the oil which enables it to penetrate the skin, suggest it may be suitable for topical therapeutic use in the treatment of fungal mucosal and cutaneous infections.

Anticandidal activity of SPA-S-843, a new polyenic drug.

The activity of a new, soluble and stable polyene (SPA-S-843) against Candida albicans was assessed by contact and culture tests and by inhibition of germ-tube formation. The drug demonstrated a higher contact activity and lower MICs than amphotericin B. This antimicrobial activity was more evident under acid pH and low ionic strength. In addition, the ability of SPA-S-843 to inhibit Candida sp. conversion from yeast to mycelial form was evident at low drug concentrations (0.25-0.62 mg/L).

Propyl gallate increases in vitro antifungal imidazole activity against Candida albicans.

We looked at the in vitro effect of an antioxidant, propyl gallate (PG), on the antifungal activity of miconazole sulphosalicylate, econazole sulphosalicylate and ketoconazole against 40 clinical isolates of Candida albicans. The combination of imidazole and PG gave MIC values 10-150 times lower than those of imidazole alone. The optimal conditions for this enhanced activity were pH 6.2-8.0 and a fungal cell concentration lower than 3 x 10(5) cells/ml. The mechanism of the interaction between imidazole and PG is not known but may be as a result of an effect of PG on the P-450 cytochrome. Theoretically this combination could reduce the side effects of long treatment with imidazoles and lower the risk of resistance to these antifungal drugs.

Antifungal activity of ketoconazole and other azoles against Malassezia furfur in vitro and in vivo.

The in vitro activity of several antifungal agents (ketoconazole, miconazole, econazole, fenticonazole, itraconazole, fluconazole) in routine clinical use against Malassezia furfur infections has been studied with freshly isolated strains of M. furfur from pityriasis versicolor lesions. The results indicate that the drugs tested exert a good activity, and both ketoconazole and itraconazole appear very active (0.8 mg/l respectively). Hair samples from the beards of volunteer patients affected by pityriasis versicolor but otherwise healthy were examined to determine ketoconazole levels during oral therapy (one or two 200 mg tablets daily). It was shown that the drug progressively accumulates in the beard, reaching levels proportional to the dose administered, although blood levels did not increase in parallel. The study of drug concentration profile has evidenced a long ketoconazole persistence in the beard at therapeutic levels. In conclusion, the possibility of reaching high and lasting ketoconazole levels in the keratin layer of the epidermis indicates that systemic ketoconazole therapy could be useful for eradication of M. furfur in patients affected by pityriasis versicolor.

In vivo and in vitro antifungal activity of the polyene derivative SPA-S-753 against encapsulated form of Cryptococcus neoformans.

The in vitro and in vivo activity of SPA-S-753 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate), a new water soluble polyene, was compared with amphotericin B against Cryptococcus neoformans in encapsulated (K) and nonencapsulated (N) morphological forms. In vitro tests against 17 isolates of C. neoformans (in K or N form) showed that SPA-S-753 activity is about ten times higher than that of amphotericin B. In direct contact tests the SPA-S-753 cytocidal action was significantly higher than that of amphotericin B; the K cells are, however, less sensitive to the cytocidal action exerted by the two polyenes even when using concentrations 4-fold higher than those used against the N cells and they present a smaller potassium ion release. The cytocidal activity of the two polyenes is favoured by a low electrolyte concentration and an acid pH. SPA-S-753 microbicidal activity by contact in vivo, in mice infected with C. neoformans N cells by i.p. route, is more powerful than that of amphotericin B. In protection tests in mice infected with 10 LD50 of C. neoformans K cells, SPA-S-753 action is again more powerful, but not to a significant degree, than that of amphotericin B. In conclusion, both substances showed a reduced in vitro and in vivo activity against C. neoformans in the K morphological form. Nevertheless our results demonstrate that SPA-S-753 exerts an antifungal overall activity that is more effective than that of amphotericin B under similar experimental conditions.

Antifungal agents. 9. 3-Aryl-4-[alpha-(1H-imidazol-1-yl)arylmethyl]pyrroles: a new class of potent anti-Candida agents.

A new class of potent antifungal agents, namely, 3-aryl-4-[alpha-(1H-imidazol-1-yl)arylmethyl]-pyrroles, is described. These compounds are related to bifonazole and pyrrolnitrin, two compounds belonging to the class of antimycotic drugs. The synthesis of the title pyrroles has been performed starting from 1,3-diaryl-2-propen-1-ones, which were reacted with tosylmethyl isocyanide to give 3-aroyl-4-arylpyrroles. Reduction of the resulting compounds by lithium aluminum hydride furnished the related alcohols, which were treated with 1,1'-carbonyldimidazole to afford the required imidazole derivatives. Forty-four new pyrroles which incorporate an (arylmethyl)imidazole moiety in the 3-arylpyrrole structure were prepared by the above procedure and tested in vitro against Candida albicans and Candida spp. Among test compounds, 10 were found to be highly active against C. albicans. The most active derivative (27) was twice as potent (MIC90) as bifonazole, and its activity was 4 times greater than those of miconazole and ketoconazole. The other nine compounds showed antifungal activity of the same order of that of bifonazole and were ca. 2 times as active as miconazole and ketoconazole. Derivatives 21 and 27 tested in vivo against C. albicans A170 were shown to be highly effective in rabbit skin candidosis. Pharmacological studies on compounds 27 and other related pyrroles (19, 35, 36, 38, 39, and 49) are in progress to select one of them as a potential candidate for clinical experiments.

Antimicrobial contact activity of econazole sulfosalicylate.

The aim of this investigation was to compare the contact action of econazole sulfosalicylate (E-SSA) on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, T. cutaneum, Pityrosporum sp.), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Citrobacter freundii) with that exerted by econazole nitrate (E-NIT). The results show E-SSA activity greater than E-NIT (in particular against mycetes and Gram-negative bacteria). The E-SSA contact activity trials illustrated certain properties of this imidazole sulfosolicylate such as: absence of latency time, antimicrobial activity proportional to its concentration, when a high concentration is used, given the limiting influence of pH and ionic strength of the medium. The higher E-SSA contact activity, in relation to E-NIT, can be correlated to its greater lipophylia considering also the lipophylic properties of SSA and the scarce dissociation of E-SSA.

Increased in vitro sensitivity of Candida albicans to fluconazole.

Sodium dioctyl sulfosuccinate (SDSS), an anionic surfactant used at a non-antimicrobial concentration, increased the sensitivity of Candida albicans to fluconazole in complex media (such as Sabouraud). The conditions were assessed to determine the in vitro sensitivity to fluconazole. In this connection, the use of a liquid medium at a non-alkaline pH is important. The presence of SDSS in complex media does not seem to affect the neutralization of a particular substances but favours the activity of fluconazole.

Investigations of the activity by contact of miconazole sulfosalicylate.

The in-vitro antimicrobial activity of miconazole sulfosalicylate (M.SSA) has been investigated on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus niger, Trichophyton mentagrophytes), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Proteus vulgaris) in comparison with miconazole nitrate (M.NIT). The results showed M.SSA has a greater activity than M.NIT, particularly on mycetes and Gram-negative bacteria. The study of activity by contact with M.SSA showed some characteristics of this sulfosalicylate imidazole, such as the lack of a latency time, an antimicrobic action related directly to the concentration, the limited influence of pH and ionic strength of medium used. The greater activity by contact of M.SSA than M.NIT could be related to its higher lipophilia (due also to the lipophilic characteristics of SSA) and, therefore, to increased interaction with the cell membrane.

[Antimicrobial activity exerted by sodium dichloroisocyanurate]. / Studio dell'attività antimicrobica esercitata dal dicloroisocianurato di sodio.

Sodium dichloroisocyanurate is a chlorinated cleaner. It was used for swimming pool sanitation and for the sterilisation of linen. Not recently ago sodium dichloroisocyanurate has substituted hypochlorite for the sterilisation of infant feeding bottles and teats. Sodium dichloroisocyanurate is soluble in water; this condition causes the hydrolysis of sodium dichloroisocyanurate in hypochlorous acid, that is the active agent, isocyanurate and isocyanurate chlorine. These compounds form a chlorine protein that carry out microbicidal activity. In a toxicology study has been shown that no severe changes in the normal metabolic function occurred, furthermore sodium dichloroisocyanurate has not shown teratogenic effects at the concentration of 200 mg/kg. The antimicrobial activity of sodium dichloroisocyanurate was evaluated against Gram negative bacteria such as E. coli or Salmonella typhimurium and against some fungi. This study illustrates a rapid antimicrobial activity using concentrations. Our study concentrated on the antimicrobial activity of sodium dichloroisocyanurate in some experimental conditions. We tested 66 strains of fungi, 28 Gram positive bacteria and 29 Gram negative bacteria. We also evaluated the antimicrobial activity of sodium dichloroisocyanurate against protozoa such as Trichomonas vaginalis. The antimicrobial activity was evaluated in cultural conditions and non cultural conditions; in these experiments we observed similar action in both the commercial product and pure substance. In cultural conditions sodium dichloroisocyanurate shows a good activity against fungi and bacteria, moreover it can be observed that the serum didn't interfere with its activity. In a non cultural condition the Candida was killed rapidly by the sodium dichloroisocyanurate but this activity is influenced by the growth phase of the yeast. Against mycelial form such as Penicillium and Aspergillus the sodium dichloroisocyanurate needs a longer contact time than yeast form for its activity. It is interesting to note that well known bacteria, that are resistant to the common antimicrobial agents, such as Pseudomonas aeruginosa, were inhibited by sodium dichloroisocyanurate in a rapid bactericidal action. Our data demonstrates that no significant adverse influence on the activity of sodium dichloroisocyanurate was shown by pH and by temperature even if in some experimental conditions increased activity was noticed at pH = 6.6. The sodium dichloroisocyanurate has demonstrated good activity against Trichomonas vaginalis. This fact extends the broad-spectrum activity of sodium dichloroisocyanurate to the protozoa. In conclusion, sodium dichloroisocyanurate has demonstrated a good activity against all tested strains, furthermore its activity did not decrease in the presence of 1% of organic substance (serum etc.).(ABSTRACT TRUNCATED AT 400 WORDS)

[Antimicrobial characteristics of a tincture of dequalinium chloride]. / Caratteristiche antimicrobiche di una tintura al dequalinio cloruro.

Dequalinium is a quaternary ammonium salt. From about 30 years Dequalinium (D.C.) was used in the treatment of the initial respiratory organs infections. It can be given orally and topically yet it cannot be given systemically cause its probable systemic toxicity. D.C. has a wide range of antimicrobial activity that is extended to Gram positive, Gram negative bacteria, protozoa and yeast. Its mechanism of action is directed to the cytoplasmatic membrane where D.C. caused its damage and consequently release of cellular components. Our study has been evaluated the antimicrobial activity of D.C. both as commercial product that pure substance. We tested 27 Gram positive bacteria, 49 Gram negative bacteria, 83 strains of fungi, we also tested the antimicrobial activity of D.C. commercial product and pure substance against 8 strains of protozoa; Trichomonas vaginalis. The antimicrobial activity was estimated in some experimental conditions, (cultural and no cultural conditions); in these experiments we can observed that the commercial product presents higher activity than pure substance. In cultural condition commercial product presents antimicrobial activity against Gram positive and negative bacteria and yeast; its interesting to evaluate that bacteria, that are resistant to the common antimicrobial agents were inhibited by D.C. tinture and pure substances. Our data exhibit that serum didn't interfere until the 2% concentration with the antimicrobial activity of D.C., moreover this antimicrobial activity is not influenced by the inoculum size until 10(5) cell/ml. D.C. presents higher activity at alkaline pH than acid pH but strains of C. albicans were killed by D.C. at acid pH. In no cultural conditions D.C. has demonstrated a rapid antimicrobial activity in short contact time (15 minute); the cells of some microorganisms were killed in 60 minutes. Against mycelial form, the commercial product demonstrates good activity higher than pure substance. The activity of D.C. against the formation of germ-tube from blastospores of C. albicans in N-acetyl-glucosamine solution (no culture medium) was markedly high; this is very important because in C. albicans the germ-tube production and yeast-mycelial conversion are prominent for pathogenicity and resistance to host defences. Our data demonstrate the good activity of D.C. against Trichomonas vaginalis; we can also observed that the antimicrobial activity of commercial product is higher than pure substance.(ABSTRACT TRUNCATED AT 400 WORDS)

The antibacterial activity of a new 3-azinomethyl-rifamycin.

The new 3-azinomethyl-rifamycin, SPA-S-565, was shown to exert an effective antibacterial activity in vitro comparable to that of rifampicin. In fact, the antibacterial activity of SPA-S-565 against numerous Gram-positive cocci belonging to Staphylococcus and Streptococcus species as well as against 20 strains of Mycobacterium tuberculosis, was similar to that of rifampicin. In Swiss albino mice intraperitoneally infected with Staphylococcus aureus Oxford strain or Streptococcus pyogenes, the protective activity of SPA-S-565 and rifampicin was quite remarkable, and no significant difference was noted between the two antibiotics. In M. tuberculosis-infected mice treated with the antibacterial agents every seven days, the protection exerted by SPA-S-565 was significantly greater than that exerted by rifampicin.

A study of the antifungal activity of LY121019, a new echinocandin derivative.

LY121019 is a cyclic peptide antibiotic of the echinocandin group, which is characterized by strong anti-Candida activity (in particular against Candida albicans) as well as by low experimental toxicity. Its anti-Candida activity is thought to be due to an inhibition of the synthesis of beta-glucan, an essential cell wall polysaccharide. The different composition of culture media or the presence of animal serum did not show adverse effects on LY121019's anti-Candida activity and the addition of reducing compounds such as cysteine and hydroquinone did not manifest a negative influence. Analogously the anti-Candida activity was not influenced when C. albicans was grown under aeration. The activity of LY121019 was very high against the mycelial form of C. albicans even when this form was developed in the presence of animal serum.

Itraconazole: increased activity by chlorhexidine.

Chlorhexidine increases the activity of itraconazole against Candida isolates; itraconazole-chlorhexidine combinations show synergistic activity in culture media. The activity of itraconazole is discussed.

Itraconazole activity against fungal germination.

Itraconazole was found to be superior to ketoconazole in its antifungal activity in vitro against Hyphomycetes and Candida. In particular, complete inhibition of germination of Candida albicans and Aspergillus spp. by a lower dose of itraconazole can explain the better activity in vivo of this drug.

Microbiological perspective of ketoconazole.

The analysis of the results obtained in our trials, which took into account different experimental conditions, suggests that ketoconazole is a very effective anti-Candida drug. In particular, ketoconazole inhibits the development of the hyphal form of C. albicans which is highly invasive. In our trials, we were also able to demonstrate that it is possible to extend ketoconazole's range of action to gram-negative bacteria, if the drug is used in appropriate pharmaceutical forms. Moreover, its in vivo efficacy against dermatophytes and ifomycetes can also be explained by its ability to concentrate in keratinized tissues. From the investigations carried out on leukocyte populations, it has also been demonstrated that ketoconazole does not negatively interfere with the cell defense mechanisms of the host. In fact, the opsonic index and intraphagocytic killing do not significantly change in the presence of ketoconazole in therapeutic doses.

[Antibacterial and antifungal agents. IV. Synthesis and antifungal activity of econazole analogs with pyrrole structure]. / Ricerche su agenti antibatterici ed antifungini. Nota IV--Sintesi ed attività antifungina di analoghi dell'econazolo a struttura pirrolica.

The synthesis of analogues of antifungal econazole with a pyrrole moiety starting from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanone and from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanol is described. Results of antimicrobial screening of the new derivatives in comparison with econazole are also reported.