Effect of Candida morphology on amphotericin B susceptibility

Nugent, Kenneth; Couchot, Kendra R.; Gray, Lynn D.

doi:10.1128/aac.31.2.335

Cited by 9 publications

(9 citation statements)

References 11 publications

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“…The intracellular efficacies of the antifungal agents were determined in terms of inhibition of germ tube formation as well as effective killing of C. albicans intracellularly. With AmB, inhibition of the development of germ tubes was found at concentrations lower than those required for killing of intracellular C. albicans, which has also been reported by others (25,26,38). After an increase in the ratio of infection, slightly increased AmB concentrations were required to obtain both effects.…”

Section: Discussionsupporting

confidence: 59%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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The effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans were studied. With respect to the extracellular growth of C. albicans, antifungal activity was measured in terms of MICs and minimal fungicidal concentrations as well as by determination of the concentration that effectively killed (>99.9%) C. albicans in the absence or presence (amphotericin B only) of serum. Amphotericin B was highly active in terms of killing, even at an increased inoculum size. In the presence of serum, amphotericin B activity was substantially reduced. For fluconazole, activity was restricted to inhibition of fungal growth, even after the inoculum size was reduced. With respect to the intracellular growth of C. albicans, antifungal activity was measured by using monolayers of murine peritoneal macrophages infected with C. albicans and was measured in terms of inhibition of germ tube formation as well'as effective killing (>99%) of C. albicans. Amphotericin B was highly active against C. albicans. At an increased ratio of infection, amphotericin B activity was slightly reduced. Fluconazole had no antifungal activity. Neither a reduction in the ratio of infection nor exposure of C. albicans to fluconaz'ole prior to macrophage ingestion resulted in activity against intracellular C. albicans by fluconazole. Previous exposure of C. albicans to amphotericin B resulted in increased intracellular activity of amphotericin B. The. intracellular antifungal activity of the combination of fluconazole with amphotericin B was les than that of amphotericin B alone. Amphotericin B showed fungicidal activity against C. albicans growing both extracellularly and intracellularly, whereas fluconazole inhibited growth only of extracellular C. albicans. A slight antagonistic effect between fluconazole and aiflphotericin B was found with respect to intracellular as well as extracellular C. albicans.Deep-seated candidal infections are an important cause of morbidity and mortality in immunocompromised patients (15,21,22). The current drug of choice for most systemic mycoses is still amphotericin B (AmB), but its use is restricted by a variety of toxic side effects (6,13,15,21,22). Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37). Recently, the antifungal efficacy of Flu was demonstrated in persistently granulocytopenic rabbits when it was used for prevention or early treatment (39,40). Little is still known, however, on the role of Flu in the treatment of systemic candidiasis in immunocompromised patients. Since the host defense mechanisms in these patients are severely impaired, the intrinsic antifungal activity of the antifungal agent is of great importance for effective treatment. Unfortunately, standardized in vitro methods for assessment of ...

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Section: Discussionsupporting

confidence: 59%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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“…Although our results with respect to the inhibition of germ tube formation and elongation were consistent with observations reported by others for AmB (Nugent and Couchot 1986;Nugent et al 1987;Schaude et al 1987) and the imidazoles (Borgers et al 1979(Borgers et al , 1983Davies and Marriott 1981;Odds et al 1985;Shibl 1985;Sobel and Obedeanu 1983), correlating these events to subsequent reductions in the in vitro interaction of C. albicans with mammalian cells have not been previously reported. The results presented here also seem to indicate that while germ tube formation may be a prerequisite for fibroblast infection, modification of germinated cells by AmB may be sufficient to prevent yeast-fibroblast interactions.…”

Section: Effect Of Amb On Germ Tube Elongationsupporting

confidence: 90%

“…Our results also suggested that infection correlated with blastoconidial germination. Since recent reports have demonstrated that sublethal concentrations of amphotericin B (AmB) inhibited blastoconidial germination (Nugent and Couchot 1986;Nugent et al 1987;Schaude et al 1987), we tested the effects of sublethal amounts of ArnB on the germination of our clinical isolates and on their subsequent ability to interact with fibroblastic monolayer cultures. This report describes the results of these experiments.…”

Section: Introductionmentioning

confidence: 99%

The effects of amphotericin B on the interaction of Candida albicans with fibroblast cultures

Merkel¹,

Phelps²

1989

Can. J. Microbiol.

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Sublethal amounts of amphotericin B inhibited the interaction of Candida albicans with cultured fibroblasts. Different C. albicans clinical isolates exhibited varying degrees of sensitivity to the drug, but those isolates that were the most infective in control cultures appeared to be the most resistant to amphotericin B mediated infection inhibition. Although amphotericin B inhibited germ tube formation at the sublethal concentration of 0.3 microgram/mL, lower concentrations inhibited infection without preventing germination. The extent of this latter activity varied with the isolate and amphotericin B concentration and appeared to be related to sublethal effects on germinated yeasts. While amphotericin B effectively prevented new fibroblast infection, it did not dissociate those yeasts which had established an infection before its addition.

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“…There are also differences in composition of the plasma membranes of yeast and filamentous forms of C. albicans (6,32). Yeast organisms with germ tubes were more susceptible to the action of amphotericin B than nongerminated yeast organisms (34). However, it could be argued that the yeast organisms in the process of producing germ tubes were those more actively growing.…”

Section: Discussionmentioning

confidence: 81%

Action of Chlorhexidine Digluconate against Yeast and Filamentous Forms in an Early-StageCandida albicansBiofilm

Suci

Tyler

2002

Antimicrob Agents Chemother

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An in situ method for sensitive detection of differences in the action of chlorhexidine against subpopulations of cells in Candida albicans biofilms is described. Detection relies on monitoring the kinetics of propidium iodide (PI) penetration into the cytoplasm of individual cells during dosing with chlorhexidine. Accurate estimation of the time for delivery of the dosing concentration to the substratum was facilitated by using a flow cell system for which transport to the interfacial region was previously characterized. A model was developed to quantify rates of PI penetration based on the shape of the kinetic data curves. Yeast were seeded onto the substratum, and biofilm formation was monitored microscopically for 3 h. During this period a portion of the yeast germinated, producing filamentous forms (both hyphae and pseudohyphae). When the population was subdivided on the basis of cell morphology, rates of PI penetration into filamentous forms appeared to be substantially higher than for yeast forms. Based on the model, rates of penetration were assigned to individual cells. These data indicated that the difference in rates between the two subpopulations was statistically significant (unpaired t test, P < 0.0001). A histogram of rates and analysis of variance indicated that rates were approximately equally distributed among different filamentous forms and between apical and subapical segments of filamentous forms.

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Effect of Candida morphology on amphotericin B susceptibility

Cited by 9 publications

References 11 publications

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

The effects of amphotericin B on the interaction of Candida albicans with fibroblast cultures

Action of Chlorhexidine Digluconate against Yeast and Filamentous Forms in an Early-StageCandida albicansBiofilm

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