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PubMed2001

In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi.

The NCCLS proposed standard M38-P describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds); however, standard conditions are not available for testing their fungicidal activities (minimum fungicidal or lethal concentrations [MFCs]). This study evaluated the in vitro fungistatic and fungicidal activities of voriconazole, itraconazole, and amphotericin B against 260 common and emerging molds (174 Aspergillus sp. isolates [five species], 23 Fusarium sp. isolates [three species], 6 Paecilomyces lilacinus isolates, 6 Rhizopus arrhizus isolates, 23 Scedosporium sp. isolates, 23 dematiaceous fungi, and 5 Trichoderma longibrachiatum isolates). MICs were determined by following the NCCLS M38-P broth microdilution method. MFCs were the lowest drug dilutions that resulted in fewer than three colonies. Voriconazole showed similar or better fungicidal activity (MFC at which 90% of isolates tested are killed [MFC(90)], 1 to 2 microg/ml) than the reference agents for Aspergillus spp. with the exception of Aspergillus terreus (MFC(90) of voriconazole and amphotericin B, >8 microg/ml). The voriconazole geometric mean (G mean) MFC for Scedosporium apiospermum was lower (2.52 microg/ml) than those of the other two agents (5.75 to 7.5 microg/ml). In contrast, amphotericin B and itraconazole G mean MFCs for R. arrhizus were 2.1 to 2.2 microg/ml, but that for voriconazole was >8 microg/ml. Little or no fungicidal activity was shown for Fusarium spp. (2 to >8 microg/ml) and Scedosporium prolificans (>8 microg/ml) by the three agents, but voriconazole had some activity against P. lilacinus and T. longibrachiatum (G mean MFCs, 1.8 and 4 microg/ml, respectively). The fungicidal activity of the three agents was similar (G mean MFC, 1.83 to 2.36 microg/ml) for the dematiaceous fungi with the exception of the azole MFCs (>8 microg/ml) for some Bipolaris spicifera and Dactylaria constricta var. gallopava. These data extend and corroborate the available fungicidal results for the three agents. The role of the MFC as a predictor of clinical outcome needs to be established in clinical trials by following standardized testing conditions for determination of these in vitro values.

Amphotericin B↗
PubMed2005

Evaluation of fungicides for the control of carrot cavity spot.

Cavity spot is one of the most common and serious diseases of carrot (Daucus carota L). The disease, caused by different species of Pythium, including P. violae Chesters & Hickman, P. sulcatum Pratt & Mitchell and P. sylvaticum Campbell & Hendrix, leads to frequent high rejection rates during grading worldwide. In the area of the city of Québec, the disease is caused mainly by P. sulcatum, P. sylvaticum and P. macrosporum Vaartaja & van der Plaats-Niterink. Cavity spot can be controlled with metalaxyl, but reports are emerging that this treatment show little or no efficacy in many regions. This situation reinforces the need for alternative fungicides. The objectives of the present study were: (1) to determine the sensitivity of 14 pathogenic isolates of P. sulcatum, P. sylvaticum and P. macrosporum collected from carrots produced in the area of the city of Québec to different broad-spectrum and oomycete-specific fungicides (chlorothalonil, etridiazole, fludioxonil, fosetyl-Al, metalaxyl, zoxamide), (2) to evaluate the efficacy of the fungicides in controlling cavity spot, and (3) to evaluate the risk of resistance development of isolates with the best-performing fungicide(s). The determination of EC50 for the fungicides tested showed that most isolates were highly sensitive to both metalaxyl and zoxamide but insensitive to fludioxonil, fosetyl-Al and chlorothalonil. In greenhouse assays, only zoxamide provided significant and consistent disease control as measured by the number of cavity spot lesions caused by P. sulcatum. Investigations into the risk of resistance development to zoxamide showed that, for specific isolates, repeated exposure to the fungicide resulted in a loss of sensitivity.

Daucus carota↗
PubMed2006

Fungicide control of mushroom cobweb disease caused by Cladobotryum strains with different benzimidazole resistance profiles.

The benzimidazole fungicides thiabendazole and carbendazim, and the imidazole fungicide prochloraz-Mn, were tested for their efficacy in controlling cobweb disease of mushrooms caused by two Cladobotryum isolates. Isolate 202A was benzimidazole-sensitive in vitro and cobweb growth on the casing was well controlled by both benzimidazole fungicides in cropping experiments. Carbendazim also controlled the development of spotting symptoms much more effectively than thiabendazole. A second isolate (192B1) was benzimidazole-resistant and was highly resistant to thiabendazole in vitro but it showed some sensitivity to carbendazim in vitro at moderate to high concentrations. Despite this, carbendazim did not control disease symptoms in cropping experiments, confirming that isolate 192B1 is cross-resistant to other benzimidazole fungicides. Both isolates showed some sensitivity to prochloraz-Mn in vitro. This fungicide gave between 45% and 65% control of cobweb growth on the casing caused by either 202A or 192B1 but gave no control of spotting symptoms. Reducing the fungicide application volume did not give enhanced disease control. The emergence of benzimidazole resistance reduces the value of benzimidazoles in the control of mushroom pathogens. However, the lack of effective alternatives means they continue to have utility in cases where pathogens are still sensitive but this requires regular monitoring of pathogen populations for resistance.

Agaricus↗
PubMed2006

Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence.

Drug transporters are membrane proteins that provide protection for organisms against natural toxic products and fungicides. In plant pathogens, drug transporters function in baseline sensitivity to fungicides, multidrug resistance (MDR) and virulence on host plants. This paper describes drug transporters of the filamentous fungi Aspergillus nidulans (Eidam) Winter, Botrytis cinerea Pers and Mycosphaerella graminicola (Fückel) Schroter that function in fungicide sensitivity and resistance. The fungi possess ATP-binding cassette (ABC) drug transporters that mediate MDR to fungicides in laboratory mutants. Similar mutants are not pronounced in field resistance to most classes of fungicide but may play a role in resistance to azoles. MDR may also explain historical cases of resistance to aromatic hydrocarbon fungicides and dodine. In clinical situations, MDR development in Candida albicans (Robin) Berkhout mediated by ABC transporters in patients suffering from candidiasis is common after prolonged treatment with azoles. Factors that can explain this striking difference between agricultural and clinical situations are discussed. Attention is also paid to the risk of MDR development in plant pathogens in the future. Finally, the paper describes the impact of fungal drug transporters on drug discovery.

Agriculture↗
PubMed1998

The accumulation and histological effects of organometallic fungicides Propineb and Maneb in the kidneys of fetus and female rats during pregnancy.

Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the kidneys of fetus and fungicide-treated pregnant females showed a variety of histopathological effects. Moreover, the analysis of zinc (Zn) and manganese (Mn) concentrations (using inductively coupled plasma-atomic emission spectrometry) in the kidneys of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the kidney were higher than those of controls. However, the renal metal concentrations were significantly increased in the litters subjected to the fungicides during gestation, indicating that high levels of the trace metals in the organ of fetus may well be due to the fungicides easily passing the placental barrier.

Animals↗
PubMed2002

Sorption behavior of triazole fungicides in Indian soils and its correlation with soil properties.

Adsorption-desorption of triazole fungicides, hexaconazole [2-(2,4-dichlorophenyl)-1-(1H-1,2,4,-triazol-1-yl) hexan-2-ol], triadimefon [1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl) butan-2-one], and penconazole[1-(2,4-dichloro-beta-propyl phenethyl)-1H-1,2,4-triazole] was studied in five Indian soils using batch method. The adsorption isotherms fitted very well to the Freundlich equation. Adsorption of various triazole fungicides increased in this order: triadimefon > hexaconazole > penconazole. The product of the Freundlich adsorption constants, K(f)(1/n), showed good correlation with the soil organic carbon (OC) content, suggesting that soil OC is the main controlling factor for triazoles adsorption. Clay and silt content of the soil also affected the adsorption constants. Adsorption of hexaconazole and triadimefon was nearly reversible in two low OC soils (soil 3, soil 5) where 90-100% of the sorbed fungicides was released in a single washing step. Otherwise, desorption of triazole fungicides showed hysteresis, and 30-60% of the triazole fungicides were retained by the soil after single washing. IR spectra showed that H-bonds and charge-transfer bonds between humic acid and fungicides probably operated as mechanisms of adsorption.

Adsorption↗
PubMed2004

Effect of the addition of wine distillery wastes to vineyard soils on the adsorption and mobility of fungicides.

In the present work, a study was made of the effect of the addition of liquid and solid wine distillery wastes (WLW and WSW) to vineyard soils on the adsorption and leaching of penconazole and metalaxyl, two fungicides of different hydrophobic character that are widely used in vine cultivation. The study of these processes is of great interest, since currently the green filter system is implemented simultaneously in vine cultivation and as an alternative to classic purification methods of such organic wastes. Three vineyard soils selected from the La Rioja region (NW Spain) were used. Adsorption isotherms of the 14C-labeled fungicides by the soils in aqueous medium and in WLW medium were obtained, together with the percolation curves of the fungicides in packed soil columns under saturated flow conditions. The adsorption and leaching of metalaxyl in a soil amended with WSW were also studied. The Freundlich Kf constants indicated an increase in the adsorption of both fungicides by the soils in WLW medium as compared to aqueous medium. The amounts of penconazole leached in the three soils when they were washed with water and WLW ranged between 3.18 and 39.3% and between 2.00 and 10.4%, respectively, of the total fungicide added to the columns. In the case of metalaxyl, these amounts represented 69.1-100 and 91.6-117%. Variations were also observed in the shape and parameters of the breakthrough curves obtained in both systems and in the presence of WSW. The soluble organic compounds of WLW must be retained by the soil components, creating new adsorbent hydrophobic surfaces, which increase the retention in the soil of the highly hydrophobic compound penconazole. In the case of metalaxyl, which is very water soluble, the soluble organic compounds of WLW seem to contribute to the increase in its leaching, whereas the WSW favors the opposite effect. The results obtained, indicating modifications in the adsorption and leaching of penconazole and metalaxyl in the presence of WLW and WSW, show that further studies should be carried out on the adsorption and mobility of the fungicides in soils from the vineyard zone, which in turn are used as a green filter purification system of wine wastes.

Adsorption↗
PubMed2002

Biosorption and solubilization of copper oxychloride fungicide by Aspergillus niger and the influence of calcium.

The biosorption of copper oxychloride fungicide particulates (approximately 1 microm diameter), at concentrations ranging from 25 to 500 ppm active ingredient (ai), by pelleted mycelium of Aspergillus niger grown on Czapek Dox medium was evaluated. The concentration of the fungicide adsorbed to the mycelium, remaining suspended or solubilized in the medium, was determined by analysis of its copper content (CuF) using atomic absorption spectrophotometry (AAS). 2-day-old pellets exhibited high biosorption efficiency ranging from 97 +/- 1.0 to 88 +/- 1.2% of the initially added fungicide concentrations, respectively, within 10 min. However, under the same conditions, amounts of the removed fungicide by 6-day-old mycelial pellets were significantly lower and ranged from 0.5 +/- 0.03 to 0.15 +/- 0.01%. Scanning electron microscopy studies of 2-day-old pellets supplemented with the fungicide revealed predominant aggregations of clumps and dense particulates on the hyphal tips. The adsorbed CuF of 125 ppm ai fungicide subsequently decreased from 7.5 +/- 0.5 to 2.1 +/- 0.1 micromol Cu (mg dry wt)(-1) after 12 h incubation. Simultaneously, the soluble portion of CuF remaining in the medium increased from 0.9 +/- 0.6 to 4.9 +/- 0.2 micromol Cu ml(-1). The presence of 50 mM CaCl2 resulted in a decrease of the adsorbed CuF to 3.5 +/- 0.5 micromol Cu (mg dry wt)(-1) and solubilized copper in the medium increased to 5.9 +/- 0.8 micro mol Cu ml(-1). Additionally, the cellular copper contents attained after 2 h were 0.08 +/- 0.01 and 0.16 +/- 0.007 micromol Cu (mg dry wt)(-1) in absence and presence of calcium, respectively. The addition of calcium to glucose-starved pellets greatly increased the medium [H+] which was conclusively discussed in relation to Ca2+/H+ exchange capacity of the fungal cells. These results are of potential environmental, biotechnological and agricultural importance.

Absorption↗
PubMed1993

Effect of fungicides, captafol and chlorothalonil, on microbial and enzymatic activities in mineral soil.

Tests were conducted to determine the effects of fungicides, captafol and chlorothalonil, on microbial and enzymatic activities in sandy loam. The results indicated that when captafol or chlorothalonil was added to the sandy loam, bacterial and fungicidal populations initially decreased with the treatments but recovered rapidly to levels similar to those in the controls. No inhibition on oxidation of soil ammonia or organic sulfur was observed. The fungicide treatments significantly increased oxygen consumption from the decomposition of organic matter indigenous to the soil. Both fungicides suppressed invertase and amylase for 1 day. However, the inhibitory effect disappeared after 2 days. Captafol depressed dehydrogenase for 4 days and recovered to equal to that of control after 7 days. No inhibitory effect on urease and phosphatase was shown with the fungicidal treatments. Although some stimulatory influences of fungicides on microbial and enzymatic activities were found in the soil, in no instance were the effects dramatic or sufficient enough to be considered important to soil fertility.

Bacteria↗
PubMed2003

Fungicide sprays can injure the stigmatic surface during receptivity in almond flowers.

Fungicides can be detrimental to flower development, pollen function and fruit set in a number of crops. Almond is a self-incompatible nut crop that has a fruit set of only approx. 30 % of the total number of flowers. Thus, interference of pollination and fertilization by fungicide sprays is of concern, and identification of chemicals having the least detrimental effects would be desirable. The objective of this study was to evaluate the effect of fungicide sprays on stigma morphology in almond using a laboratory spray apparatus that simulated field applications. Four fungicides (azoxystrobin, myclobutanil, iprodione and cyprodinil) were applied, and fresh, unfixed stigmatic surfaces were observed using a scanning electron microscope at 4 and 24 h after spraying. Increased exudate accumulation was induced by azoxystrobin at both time periods, and localized damage and collapse of stigmatic cells were observed after 24 h. Damaged stigmatic papillae exhibited wrinkling, surface distortion or collapse. Likewise, myclobutanil caused significant damage to and collapse of papillae; these were more extensive at later observations. Iprodione had no effect on exudate accumulation but caused marked and severe collapse of stigmatic papillae which was pronounced at 24 h. Cyprodinil promoted a copious increase in exudate secretion and caused the most severe collapse of stigmatic cells of all the fungicides evaluated. Damage was somewhat localized at 4 h but more global at 24 h. This study has verified that certain fungicide sprays have direct detrimental effects on stigma morphology and enhance exudate production in almond flowers.

Flowers↗
PubMed2004

Effects of fungicide residues on the survival, fecundity, and predation of the mites Tetranychus urticae (Acari: Tetranychidae) and Galendromus occidentalis (Acari: Phytoseiidae).

Representative fungicides from three or four families used for management of powdery mildew and other diseases in tree fruits were evaluated for their effects on a common spider mite and predator mite species, respectively. A modified Munger cell technique was effective in measuring the response of phytophagous and predaceous mites to fungicide residues on detached leaves in the laboratory. Demethylation-inhibiting (DMI) (imidazole [triflumazole] and triazole [myclobutanil]) and strobilurin (trifloxystrobin) fungicides were not toxic to female Tetranychus urticae Koch and Galendromus occidentalis (Nesbitt), and no sublethal effects were found on fecundity and predation rate after 3-5-d exposure to residues. Benomyl, a benzimidazole fungicide, increased adult mortality and reduced fecundity for both mite species; however, it did not alter the predation rate of G. occidentalis females on T. urticae eggs and larvae. Female G. occidentalis that survived the lethal effects of benomyl and the comparison acaricide pyridaben were unimpaired in predation. Our results for benomyl substantiate those of earlier studies and provide evidence for nontoxic effects of DMI and strobilurin fungicides on mites. We propose that DMI and strobilurin fungicides are a good fit for integrated mite management programs due to conservation of phytoseiid predatory mites.

Animals↗
PubMed1998

Impaired fungicide activity in plants blocked in disease resistance signal transduction.

Fungicide action is generally assumed to be dependent on an antibiotic effect on a target pathogen, although a role for plant defense mechanisms as mediators of fungicide action has not been excluded. Here, we demonstrate that in Arabidopsis, the innate plant defense mechanism contributes to the effectiveness of fungicides. In NahG and nim1 (for noninducible immunity) Arabidopsis plants, which normally exhibit increased susceptibility to pathogens, the fungicides metalaxyl, fosetyl, and Cu(OH)2 are much less active and fail to control Peronospora parasitica. In contrast, the effectiveness of these fungicides is not altered in Arabidopsis mutants defective in the ethylene or jasmonic acid signal transduction pathways. Application of the systemic acquired resistance activator benzothiadiazole (BTH) in combination with these fungicides results in a synergistic effect on pathogen resistance in wild-type plants and an additive effect in NahG and BTH-unresponsive nim1 plants. Interestingly, BTH treatment normally induces long-lasting pathogen protection; however, in NahG plants, the protection is transient. These observations suggest that BTH treatment can compensate only partially for an impaired signal transduction pathway and support the idea that pathogen defense mechanisms are under positive feedback control. These observations are strikingly reminiscent of the reduced efficacy of antifungal agents in immunocompromised animals.

Animals↗
PubMed2002

Osmoregulation and fungicide resistance: the Neurospora crassa os-2 gene encodes a HOG1 mitogen-activated protein kinase homologue.

Neurospora crassa osmosensitive (os) mutants are sensitive to high osmolarity and therefore are unable to grow on medium containing 4% NaCl. We found that os-2 and os-5 mutants were resistant to the phenylpyrrole fungicides fludioxonil and fenpiclonil. To understand the relationship between osmoregulation and fungicide resistance, we cloned the os-2 gene by using sib selection. os-2 encodes a putative mitogen-activated protein (MAP) kinase homologous to HOG1 and can complement the osmosensitive phenotype of a Saccharomyces cerevisiae hog1 mutant. We sequenced three os-2 alleles and found that all of them were null with either frameshift or nonsense point mutations. An os-2 gene replacement mutant also was generated and was sensitive to high osmolarity and resistant to phenylpyrrole fungicides. Conversely, os-2 mutants transformed with the wild-type os-2 gene could grow on media containing 4% NaCl and were sensitive to phenylpyrrole fungicides. Fludioxonil stimulated intracellular glycerol accumulation in wild-type strains but not in os-2 mutants. Fludioxonil also caused wild-type conidia and hyphal cells to swell and burst. These results suggest that the hyperosmotic stress response pathway of N. crassa is the target of phenylpyrrole fungicides and that fungicidal effects may result from a hyperactive os-2 MAP kinase pathway.

Dioxoles↗
PubMed2002

Toxicity of a mancozeb containing fungicide formulation and CU-sulphate to chicken embryos after administration as single compounds or in combination.

Environmental pollution of metal modelled by copper-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on chicken embryos after administration as a single compounds or in combination. The test materials were injected into the air-chamber in a volume of 0.1 ml/egg on day 12 of incubation. The concentration of copper-sulphate was 0.01%. The applied concentration of Dithane M-45 fungicide formulation was 0.2%. Evaluation was done on day 19 of the hatching period. The combined administration of copper-sulphate and the fungicide formulation did not cause a significant reduction in body weight as compared to the control data and the results from individual toxicity study of the test materials. After the combined administration of copper-sulphate and the fungicide formulation the rate of embryomortality was 40%. The incidence of developmental anomalies were sporadic. Light microscopic findings exhibited a degenerative change in the liver tissue of combined administration group. Activities of GPT and GOT enzymes increased markedly in the combined administration group. In summary, it can be established that the interaction of copper-sulphate and an 80% mancozeb containing fungicide formulation (Dithane M-45) caused higher embryomortality with respect to the test of individual toxicity of copper-sulphate and fungicide in our study.

Alanine Transaminase↗
PubMed2002

The influence of fungicides on the growth of Trichoderma asperellum.

Numbers of strains of Trichoderma asperellum are known as biological control agents of certain root pathogens of tomato (Lycopersicon esculentum). The restricted use of fungicides is sometimes useful in combination with these biological control agents. Therefore some experiments were conducted to evaluate the growth of T. asperellum in the presence of fungicides as Previcur (active substance propamocarb) and Sumico (with the active substance carbendazim and diethofencarb). The influence of these fungicides was first examined in laboratory conditions. The fungus was brought on a potato dextrose agar where the fungicides Previcur, Sumico and carbendazim were added in a concentration of 0.1x, 1x and 10x the recommended dose. The growth of T. asperellum was totally inhibited by the three Sumico and carbendazim concentrations. T. asperellum knew a small but significant decrease of growth when the 10x dose of Previcur was added. Afterwards the influence of these fungicides on the fungus was tested in field conditions in the greenhouse. The fungus was applied to the roots of the tomato plant, which was grown on a rockwool medium. Previcur and Sumico were submitted to the plants using the normal procedure. The results of the tests showed that in field conditions there was no effect of the fungicide treatment on the presence of the fungus, although the laboratory tests showed the opposite for Sumico. To explain this contradiction two other experiments were conducted to follow the migration of the Sumico after treatment. A residue analysis showed that the highest concentration of Sumico was detected in the rockwool medium, and some residues were found in the drain water and the stems. Even with a 100x recommended dose of Sumico the fungus was still present the day after the treatment.

Benzimidazoles↗
PubMed2003

First detection of resistance to QoI fungicides in Mycosphaerella graminicola on winter wheat in Belgium.

A total of 740 Mycosphaerella graminicola strains were isolated between 2000 and 2002 from winter wheat F1 or F2 leaves showing Septoria leaf blotch lesions (SLB) collected mainly at the soft dough stage in fungicide trials, analysing at 12 locations in Belgium the possibilities and risks associated with the use of epoxiconazole and azoxystrobin at various doses, mixtures and application dates. Fungicide sensitivity tests were performed in microtitre plates on potato dextrose broth amended with various concentrations of azoxystrobin. A wide range of sensitivity to azoxystrobin was observed, with EC50 values ranging for 735 strains between 0.002 to 0.7 microg/ml, the highest frequency gradually shifting from EC50 classes 0.01 and 0.02 microg/ml azoxystrobin in 2000 to EC50 classes 0.02 and 0.04 microg/ml in 2002. No clear selection effect of particular fungicide use strategies was observed. Among the 382 strains isolated in 2002, five originating from 2 locations, showed azoxystrobin EC50 values >1 microg/ml. On medium amended with 100 microg/ml salicylhydroxamic acid (SHAM), 58% of the 2002 strains were strongly inhibited, which affected adequate azoxystrobin ED50 determination. This suggests widespread occurrence of M. graminicola strains relying in vitro on the alternative respiration pathway. In the presence of SHAM, strains 339 and 880 showed azoxystrobin EC50 values of 3 and >30 microg/ml, respectively. This high level of resistance to a QoI fungicide was confirmed by analysing mycelium growth inhibition on PDA. Cross-resistance to trifloxystrobin and kresoxim-methyl was demonstrated. Greenhouse assays on wheat plants revealed that control of QoI resistant strains by azoxystrobin is decreased, compared to control of sensitive ones. This highlights the risk of resistance to QoI fungicides also in M. graminicola populations, although up to now no decrease in field performance was noticed. It is recommended to delay build up of QoI resistance by an integrated approach, combining optimised fungicide use with the choice of SLB resistant cultivars and the application of farming practices promoting stubbles break down and so the reduction of the teleomorph stage.

Acrylates↗
PubMed1987

Activation of murine polymorphonuclear neutrophils for fungicidal activity by recombinant gamma interferon.

Recombinant murine gamma-interferon (IFN) was tested for its ability to enhance murine polymorphonuclear neutrophil (PMN) fungicidal activity in vitro. PMNs, elicited by intraperitoneal injection of thioglycollate 4 hr prior to collection, were treated with 0.00003-300,000 units of IFN per milliliter for 1 hr prior to challenge with yeast form Blastomyces dermatitidis. These PMNs were not fungicidal for Blastomyces in the absence of IFN; significant enhancement of PMN fungicidal activity by IFN treatment occurred in a dose-dependent manner with maximal enhancement observed at 30,000 U/ml (21% killing). Pretreatment of IFN with rabbit anti-IFN antiserum before addition to PMNs eliminated the enhancement of fungicidal activity by effective doses of IFN. PMN fungicidal activity against phagocytizable Candida albicans was significantly (P less than .001) higher (71.3 +/- 17.4%) than against B. dermatitidis. Candidacidal activity was not significantly enhanced by IFN treatment of PMNs. Exogenously added lipopolysaccharide, at levels corresponding to those found in this preparation of IFN, did not activate PMNs for enhanced fungicidal capacity. These data indicate a stimulatory role for IFN in the killing of B. dermatitidis by PMNs, suggesting that IFN is an active component of the communication between T lymphocytes and PMNs with respect to antimicrobial resistance. They suggest a natural role for IFN in host defense against blastomycosis and other fungal infections, and a possible therapeutic use for exogenous IFN in fungal disease.

Animals↗
PubMed1997

Key issues concerning fungistatic versus fungicidal drugs.

Are there any fungicidal drugs available today? A critical issue in answering this question is that of definition. The simplest, most stringent definitions identify fungistatic drugs as those that inhibit growth, whereas fungicidal drugs kill fungal pathogens. The immunocompetent host is usually far better equipped to eliminate fungal pathogens than the immunosuppressed host. Therefore, it would be especially desirable to have a truly fungicidal drug, one that absolutely kills and fungi, as a treatment option for the immunosuppressed patient. The critical question would be whether a fungicidal drug can be delivered to the target site in a concentration high enough for a sufficient time to reduce the intralesional fungal counts to zero. By this simple definition, there are no fungicidal drugs available today. However, an accepted alternative definition is that often used by the bacteriologist: Fungicidal drugs are those that lead to a reduction of 99.9% of the initial inocula. Although this less restrictive in vitro standard is more easily met, it has serious limitations. Whether the 99.9% kill should be an acceptable standard remains uncertain. As an alternative, the minimum inhibitory concentration, though indicating static activity, has served well; perhaps it should be the only information reported for fungal susceptibility testing.

Adjuvants, Immunologic↗