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PubMed1975

Long-distance bactericidal and fungicidal effectiveness of parachlorophenol and Formalin on Streptococcus faecalis and Candida albicans.

The "long-distance" bactericidal and fungicidal effectiveness of several concentrations of parachlorophenol, 25% Formalin, and 2% glutaraldehyde, all in 80% alcohol solution, has been tested in vitro on Streptococcus faecalis and Candida albicans. A concentration of at least 10% parachlorophenol in 80% alcoholic solution has the same long-distance bactericidal and fungicidal effectiveness as 25% Formalin in 80% alcoholic solution.

Candida albicans↗
PubMed2003

Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species.

Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104 Candida parapsilosis, 14 C.glabrata, 13 C.tropicalis, 15 C.krusei, and 19 C.albicans) and 36 C.dubliniensis from oropharyngeal infections. Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method. MFCs (> or =99.9% killing) were obtained following MIC determination (inoculum size, 10(4) CFU/ml) by seeding the entire volume of all clear wells. The best fungicidal activity was for C. albicans, (MFC90 1 microg/ml) and the lowest for C.parapsilosis, C.tropicalis and C.glabrata (MFC90 16 microg/ml). Although MFCs were > or =16x MIC for some isolates, including C. glabrata, the overall MFCs were > or =2x MICs. However, major differences between MICs and MFCs were observed for C.parapsilosis and C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC > or =32MIC). MFCs for C.tropicalis and C. glabrata were > or =2 microg/ml. By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for Candida spp.

Amphotericin B↗
PubMed2003

Oxidative stress induction as a cause of Ba2+-dependent fungicidal action of UMP-derivative on the yeast Shizosaccharomyces pombe.

A UMP-derivative, uridine 5'-hexadecylphosphate (UMPC16), exhibited a fungicidal action against various yeast strains including the fission yeast Schizosaccharomyces pombe in combination with Ba2+ ion. UMPC16 accelerated reactive oxygen species (ROS) generation in medium with Ba2+ ion in a dose- and time-dependent manner. Additional supplementation of Ca2+ ion into medium could suppress such a combined fungicidal action due to oxidative stress induction.

Journal Article↗
PubMedDate not supplied

Synthesis and fungicidal activity of new N,O-acyl chitosan derivatives.

Novel N,O-acyl chitosan (NOAC) derivatives were synthesized to examine their fungicidal activity against the gray mould fungus Botrytis cinerea (Leotiales: Sclerotiniaceae) and the rice leaf blast fungus Pyricularia oryzae (Teleomorph: Magnaporth grisea). The fungicidal activity was evaluated by the radial growth bioassay. NOAC derivatives were more active against the two plant pathogens than chitosan itself, and the effect was concentration dependent. Against B. cinerea, 4-chlorobutyryl chitosan (EC50=0.043%), decanoyl chitosan (EC50=0.044%), cinnamoyl chitosan (EC50=0.045%), and p-methoxybenzoyl chitosan (EC50=0.050%) were the most active (12-13-fold more active than chitosan). (Un)-substituted benzoyl chitosan derivatives were more active against B. cinerea than most of these with N,O-alkyl derivatives. Against P. oryzae chitosan derivatives with lauroyl, methoxy acetyl, methacryloyl and decanoyl were the most active.

Antifungal Agents↗
PubMed2000

Sensitizing capacity of azole derivatives: Part III. Investigations with anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump inhibitors.

BACKGROUND: More than hundred azole derivatives are used today for different purposes. The majority possess antimycotic, antibacterial, anthelmintic, and antiprotozoal properties. They are used as agricultural fungicides; topical antimycotics, and, for example, in antidandruff cosmetics. More recently the antithyroid and antiulcerative activity of certain imimidazoles and benzimidazoles also has been proven, which led to the introduction of proton pump inhibitors and antithyroid drugs to the market. OBJECTIVE: Case reports from the literature and experimental studies suggest that some of the azole derivatives possess a distinct sensitizing potency. Occupational exposure either in the pharmaceutical manufacture or in the pesticide's application by farmers caused allergic contact dermatitis (ACD). However, experimental studies in guinea pigs to determine their sensitizing capacity have been performed only sporadically. METHOD: Guinea pigs were sensitized by a modified Freund's complete adjuvant (FCA) method, with 35 azoles used as agricultural fungicides, proton pump inhibitors, antimycotics, antithyroid agents, antiprotozoals, antimicrobials, anthelmintics, and wood preservatives. RESULTS: Four azoles exhibited a strong sensitizing capacity, 3 a moderate, and 11 a weak sensitizing capacity. Seventeen derivatives remained negative. Among the strong sensitizers were the 3 proton pump inhibitors omeprazole, pantoprazole, and rabeprazole, as well as the antithyroid drug carbimazole. The latter displayed the highest sensitizing power (mean response = 2.50) of all 62 azole derivatives investigated in the present and the 2 previous experimental studies. CONCLUSION: As long as the strong sensitizing azoles are used only systemically the risk of acquiring contact hypersensitivity is low. However, if the idea should arise to use them topically, for example in ointments, tinctures, or lotions against fungal infections, skin problems will probably be observed abundantly.

Animals↗
PubMed2006

Dependence of synergistic fungicidal activity of Cu2+ and allicin, an allyl sulfur compound from garlic, on selective accumulation of the ion in the plasma membrane fraction via allicin-mediated phospholipid peroxidation.

Allicin was effective in decreasing the lethal concentration of Cu (2+) against various fungal strains including a plant pathogen, Fusarium oxysporum, so that the minimum fungicidal concentration (MFC) of the ion for the fungus could be reduced to 2 % of that detected without allicin. In Saccharomyces cerevisiae, Cu (2+) was not apparently taken up by cells when added alone at a non-lethal concentration, whereas the ion was efficiently incorporated into cells in the presence of allicin, as in the case of cells treated with the ion at a lethal concentration. Although allicin likely increased cellular permeability to Cu (2+) due to its promotive effect on plasma membrane phospholipid peroxidation, these cell-surface events did not result in endogenous reactive oxygen species (ROS) production, a typical toxic effect of the ion. Cu (2+) was detected in the cytoplasmic fraction of cells that had been treated with the ion at a lethal concentration, whereas the ion was entrapped in the plasma membrane fraction upon their treatment with the ion at a low concentration in combination with allicin. Cu (2+) could be solubilized from the plasma membrane fraction by a procedure for the extraction of hydrophobic proteins rather than the extraction of phospholipids, suggesting its complexation with a plasma membrane protein as a result of allicin treatment. Such a subcellular localization of Cu (2+) resulted in the selective leakage of intracellular K (+), but not in the disruptive damage on the plasma membrane, and was considered to underlie the synergistic fungicidal activity of Cu (2+) and allicin.

Antifungal Agents↗
PubMed2002

Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity.

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 microg ml(-1)) or F1 (100 and 200 microg ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. On the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.

Cell Culture Techniques↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor augments human monocyte fungicidal activity for Candida albicans.

The ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to augment the fungicidal activity of human monocytes for Candida albicans was evaluated. Purified human monocytes cultured with [3H]leucine-labeled C. albicans caused a dose-dependent release of the [3H]leucine. The amount of [3H]leucine released correlated with a decrease in the number of viable yeast colonies. Monocyte cytotoxicity for C. albicans was reduced by superoxide dismutase and catalase and by inhibitors of myeloperoxidase and scavengers of hydroxyl radical and single oxygen, consistent with monocyte candidacidal activity being partly dependent upon products of oxidative metabolism. Monocytes incubated with rhGM-CSF produced more superoxide anion (O2-) spontaneously and after stimulation than control monocytes (P less than .05). Enhanced O2- production was dose-dependent and specific for rhGM-CSF and could be inhibited by antibody to rhGM-CSF. In association with rhGM-CSF-induced production of O2-, the cytokine enhanced cytotoxic activity for C. albicans. These findings indicate that rhGM-CSF stimulates human monocyte fungicidal activity for C. albicans.

Candida albicans↗
PubMed1995

Interactions between human bronchoalveolar macrophages and Blastomyces dermatitidis conidia: demonstration of fungicidal and fungistatic effects.

The effects of human bronchoalveolar macrophages (BAMs) on Blastomyces dermatitidis conidia were investigated. Macrophage monolayers were incubated for 5 days with or without interferon (IFN)-gamma or macrophage colony-stimulating factor (M-CSF) before challenge with conidia for 48 h at 37 degrees C. Hyphal growth (germination) was inhibited 12% by resident BAMs (P < .05). In contrast, resident BAMs blocked conidial phase transition by 88% (P < .05). Intermediate forms, aggregates of large cells in clums (not conidia or yeasts by morphologic criteria), appeared after incubation with BAMs and grew into typical yeasts once removed from the BAMs. IFN-gamma and M-CSF inhibited the ability of BAMs to block phase transition but not germination. Human BAMs demonstrated fungicidal and fungistatic activity against B. dermatitidis conidia independent of reactive oxygen intermediates and had greater effects on phase transition than on germination. The phase transition-associated fungicidal and fungistatic activities of BAMs were inhibited by IFN-gamma and M-CSF.

Blastomyces↗
PubMed2006

Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts.

OBJECTIVES: To investigate the in vitro antifungal activity of the structurally different cathelicidin peptides SMAP-29, BMAP-27, BMAP-28, protegrin-1 (PG-1) and indolicidin. METHODS: The in vitro antifungal and fungicidal activities of these antimicrobial peptides were respectively assessed via MIC determinations and killing kinetics assays. The effects of the peptides on membrane permeabilization and morphology were evaluated by flow cytometry, intracellular ATP release measurements and scanning electron microscopy. RESULTS: All five peptides showed a potent but differential antifungal activity against more than 70 clinical isolates belonging to over 20 different species of pathogenic fungi; some of which are resistant to amphotericin B and azoles. The MIC values of the peptides ranged between 0.5 and 32 microM, with PG-1 being the most effective and having the widest spectrum of activity. Filamentous fungi were instead found to be scarcely susceptible to the action of these cathelicidin peptides. All these cathelicidins rapidly killed Candida albicans and Cryptococcus neoformans cells in a dose- and time-dependent manner. The rapid uptake of propidium iodide into treated cells and morphological alterations apparent on their cellular surfaces suggest a killing mechanism based on membrane permeabilization and damage. CONCLUSIONS: This study indicates that these five structurally varied host defence peptides are all endowed with the capacity to inactivate a number of fungal pathogens, irrespectively of their resistance to antifungal drugs, and suggests they might be potentially useful leads for the development of novel fungicidal agents.

Amino Acid Sequence↗
PubMed1988

Enhanced oxidative mechanisms in immunologically activated versus elicited polymorphonuclear neutrophils: correlations with fungicidal activity.

Peritoneal polymorphonuclear neutrophils (PMN) from mice were tested for their ability to kill the yeast form of Blastomyces dermatitidis (Bd) in vitro and for their fungicidal mechanisms. PMN elicited from immune mice by the intraperitoneal injection of non-viable Bd (referred to as immunologically activated PMN or ActPMN) showed significantly enhanced fungicidal activity in comparison with PMN elicited with thioglycollate medium (ThioPMN) [means = 44.7% (SD 12.8%) and 16.4% (SD 9.2%) killed; n = 14; p less than 0.001]. Production of superoxide anion (O2-) by ActPMN after stimulation with phorbol myristate acetate was enhanced in comparison with production by ThioPMN. Superoxide dismutase, which removes O2-, inhibited ActPMN killing by 75% (p less than 0.001) when added to cultures immediately before challenge with Bd (optimal concentration: 6000 U/ml). Sodium azide, which inhibits myeloperoxidase and scavenges singlet oxygen (1O2), and catalase, which breaks down hydrogen peroxide (H2O2), inhibited ActPMN killing by 64% (p less than 0.001) and 52% (p less than 0.001), with optimal concentrations of 1 mM and 10,000 U/ml, respectively. Two agents that both scavenge 1O2 and antagonise hypochlorous acid (HOCl-), histidine and tryptophan, were also powerful inhibitors of ActPMN killing. Quenchers of hydroxyl radical (.OH), dimethylsulfoxide and sodium benzoate, had less effect, and required higher concentrations. These data suggest that the enhanced killing of Bd by ActPMN involves one or more oxidative mechanisms, and that there is a prominent role for O2-, either directly or as a precursor of other active oxygen species, a probable role for H2O2, and possible roles for 1O2, HOCl-, and .OH.

Animals↗
PubMed2002

A strobilurin fungicide enhances the resistance of tobacco against tobacco mosaic virus and Pseudomonas syringae pv tabaci.

The strobilurin class of fungicides comprises a variety of synthetic plant-protecting compounds with broad-spectrum antifungal activity. In the present study, we demonstrate that a strobilurin fungicide, F 500 (Pyraclostrobin), enhances the resistance of tobacco (Nicotiana tabacum cv Xanthi nc) against infection by either tobacco mosaic virus (TMV) or the wildfire pathogen Pseudomonas syringae pv tabaci. F 500 was also active at enhancing TMV resistance in NahG transgenic tobacco plants unable to accumulate significant amounts of the endogenous inducer of enhanced disease resistance, salicylic acid (SA). This finding suggests that F 500 enhances TMV resistance in tobacco either by acting downstream of SA in the SA signaling mechanism or by functioning independently of SA. The latter assumption is the more likely because in infiltrated leaves, F 500 did not cause the accumulation of SA-inducible pathogenesis-related (PR)-1 proteins that often are used as conventional molecular markers for SA-induced disease resistance. However, accumulation of PR-1 proteins and the associated activation of the PR-1 genes were elicited upon TMV infection of tobacco leaves and both these responses were induced more rapidly in F 500-pretreated plants than in the water-pretreated controls. Taken together, our results suggest that F 500, in addition to exerting direct antifungal activity, may also protect plants by priming them for potentiated activation of subsequently pathogen-induced cellular defense responses.

Antifungal Agents↗
PubMed1997

Different susceptibility of three clinically isolated strains of Cryptococcus neoformans to the fungicidal effects of reactive nitrogen and oxygen intermediates: possible relationships with virulence.

We investigated the susceptibility of three clinically isolated strains of Cryptococcus neoformans with different virulences to reactive nitrogen and oxygen intermediates (RNI and ROI, respectively), representing two important mediators of macrophage microbicidal activity. All mice infected with the highly virulent strain of C. neoformans, YC-11, died within 3 to 6 weeks because of rapid multiplication of the organism in the lungs and dissemination to the brain. In contrast, a weakly virulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infected animals during the period of observation (15 weeks). The virulence of the third strain, YC-5, was intermediate between the other two strains. To examine the susceptibility of C. neoformans to the fungicidal effect of nitric oxide (NO) and superoxide anions (O2-), the organisms were exposed to these oxidants, which were chemically generated in a cell-free system. Interestingly, the number of live YC-13 yeast cells was markedly reduced after exposure to NO and O2-. In contrast, YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results demonstrate that the resistance of C. neoformans to the fungicidal effects of RNI and ROI is related to virulence, and suggest that the resistance to nitrogen- and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.

Animals↗
PubMed1994

Relevance of broad-spectrum and fungicidal activity of antifungals in the treatment of dermatomycoses.

The in vitro fungistatic and fungicidal activities of terbinafine, amorolfine and itraconazole against dermatophytes were compared. All three compounds showed very good activity against all dermatophyte species tested, but only terbinafine and amorolfine exhibited primary fungicidal activity. These two compounds were also active in vitro against other filamentous fungi which cause onychomycoses, such as Scytalidium and Scopulariopsis species.

Antifungal Agents↗
PubMed1989

Clinical efficacy and tolerability of terbinafine (Lamisil)--a new topical and systemic fungicidal drug for treatment of dermatomycoses.

Terbinafine (Lamisil) is the newest compound within a class of antimycotic drugs called allylamines. It is active against a broad range of dermatophytes and yeasts and exerts its fungicidal action by inhibiting squalene epoxidation during sterol synthesis in fungal membranes. Effective therapy (complete cure or mycological cure with minimal signs and symptoms) has been observed in 70-90% of 1200 patients treated topically with 1% cream for tinea corporis/cruris, tinea pedis, cutaneous candidiasis and pityriasis versicolor. Cure in patients treated systemically (125 mg b.i.d. orally) has been documented to be 75-90% in tinea corporis and chronic tinea pedis (plantar type), 60-70% in cutaneous candidiasis, and 90-100% in onychomycosis. Particularly noteworthy is the low rate of relapse of infection after cure of chronic dermatophyte infections, since frequent relapse is a recognized problem with presently available antifungal drugs. Terbinafine is ineffective when used systemically for pityriasis versicolor. Side-effects following oral administration of the recommended dose of 125 mg b.i.d. include gastrointestinal symptoms (3-4%), allergy (1%), and miscellaneous mild non-specific symptoms (1%). No significant haematological, hepatic or renal effects have been observed. Based on the drug's fungicidal action and the early appearance of negative cultures in these studies, a short duration therapy is predicted to be effective.

Administration, Oral↗
PubMed1986

An assessment of the fungicidal activity of antimicrobial agents used for hard-surface and skin disinfection.

Trichophyton mentagrophytes and Aspergillus niger conidia and Candida albicans blastospores were employed to assess the fungicidal activity of a range of antimicrobial agents used for hard-surface and skin disinfection in hospitals in the U.K. The antimicrobials were tested at in-use concentrations. The time taken to give greater than 99.99% kill was determined by estimating the number of survivors (cfu/ml) at a variety of time intervals after exposure of washed suspensions of spores to the disinfectants. At equivalent times the recovery in the broth was investigated. An alcoholic solution of chlorhexidine gluconate (0.02%) (Hibitane), iodine in Industrial Methylated Spirit (IMS) and a phenolic (0.36% phenols, Stericol) produced a 99.99% kill of all species within 2 min, alcoholic and aqueous solutions (10%) of povidone-iodine (Betadine) and hypochlorite (0.2%) required 10 min to give a 99.99% kill of all species tested. The preparations which contained cetrimide (Cetavlon), aqueous solutions of chlorhexidine gluconate (Hibitane) and combinations of these (Savloclens and Savlodil) were only slowly fungicidal, particularly against T. mentagrophytes spores, which was the most resistant of the three fungal species to disinfection.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Fungicidal effect of tyrothricin on Candida albicans.

Tyrothricin, a polypeptide antibiotic, is active against yeast cells. Tyrothricin was rapidly fungicidal towards Candida albicans. Concentration of four times the minimum inhibitory (25 mg l-1) reduced the yeast numbers by more than 3 log10 within 1 h. Similar results were obtained in a flow cytometric antifungal activity assay using the new two-colour probe for yeast viability, FUN-1, which measures impairment of metabolic activity. The respiratory activity of Candida albicans, measured in a XTT kinetic assay, was significantly reduced in comparison with controls by 3.12 mg l-1 of the substance. Because fungicidal concentrations of tyrothricin are locally achievable in patients, an evaluation of the local effect of tyrothricin in patients suffering from mucosal infections with Candida species should be considered.

Antifungal Agents↗
PubMedDate not supplied

Fungistatic and fungicidal activity of east African medicinal plants.

Extracts of the traditionally used medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem bark), Zanha africana (stem bark) and Spilanthes mauritiana (roots and flowers) were investigated for fungistatic and fungicidal activity against Candida spp. and Aspergillus spp. by a microtitre serial dilution technique. Entada abyssinica, T. spinosa, X. caffra, A. indica, and Z. africana showed activity against various Candida species. The minimum inhibitory concentrations (MICs) ranged from 0.006 to > 8 mg ml-1 and the minimum fungicidal concentrations (MFCs) from 0.06 to > 8 mg ml-1. Extracts from S. mauritiana (both roots and flowers) exhibited no activity against Candida spp., but against Aspergillus spp., the MIC and MFC values ranged from 0.13 to 0.25 mg ml-1 and from 0.13 to 1 mg ml-1 respectively. It is concluded that the extracts contain compounds with high antifungal potency.

Africa, Eastern↗