Antifungal Therapy of Murine
            <i>Aspergillus terreus</i>
            Infection

Graybill, John R.; Hernandez, Steve; Bocanegra, Rosie; Najvar, Laura K.

doi:10.1128/aac.48.10.3715-3719.2004

Cited by 39 publications

(25 citation statements)

References 24 publications

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“…For instance, A. terreus is frequently found to be resistant to amphotericin B in vitro as well as in vivo in animal models, even at high concentrations (210,556,574,608). Similarly, A. nidulans clinical isolates are frequently found to be resistant to amphotericin B in vitro (281).…”

Section: Aspergillus Fumigatus Drug Resistance: the Polyenesmentioning

confidence: 99%

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Shapiro

Robbins

Cowen

2011

Microbiol Mol Biol Rev

501

547

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SUMMARY Pathogenic fungi have become a leading cause of human mortality due to the increasing frequency of fungal infections in immunocompromised populations and the limited armamentarium of clinically useful antifungal drugs. Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus are the leading causes of opportunistic fungal infections. In these diverse pathogenic fungi, complex signal transduction cascades are critical for sensing environmental changes and mediating appropriate cellular responses. For C. albicans , several environmental cues regulate a morphogenetic switch from yeast to filamentous growth, a reversible transition important for virulence. Many of the signaling cascades regulating morphogenesis are also required for cells to adapt and survive the cellular stresses imposed by antifungal drugs. Many of these signaling networks are conserved in C. neoformans and A. fumigatus , which undergo distinct morphogenetic programs during specific phases of their life cycles. Furthermore, the key mechanisms of fungal drug resistance, including alterations of the drug target, overexpression of drug efflux transporters, and alteration of cellular stress responses, are conserved between these species. This review focuses on the circuitry regulating fungal morphogenesis and drug resistance and the impact of these pathways on virulence. Although the three human-pathogenic fungi highlighted in this review are those most frequently encountered in the clinic, they represent a minute fraction of fungal diversity. Exploration of the conservation and divergence of core signal transduction pathways across C. albicans , C. neoformans , and A. fumigatus provides a foundation for the study of a broader diversity of pathogenic fungi and a platform for the development of new therapeutic strategies for fungal disease.

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Section: Aspergillus Fumigatus Drug Resistance: the Polyenesmentioning

confidence: 99%

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Shapiro

Robbins

Cowen

2011

Microbiol Mol Biol Rev

501

547

View full text Add to dashboard Cite

show abstract

“…terreus has been consistently shown via in vitro antifungal susceptibility testing (213), in vivo animal models (71,223), and detailed clinical series (100,203) to be resistant to amphotericin B. In the largest clinical series, therapy with amphotericin B was directly shown to contribute to clinical failure, while therapy with voriconazole led to greater clinical success (203).…”

Section: Resistance To Drugs Exerting Cell Membrane Stress: the Polyenesmentioning

confidence: 99%

Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance

2008

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“…Despite its toxicity, amphotericin B (AMB) has been the first choice for the treatment of invasive aspergillosis for many years. However, the intrinsic resistance of A. terreus to polyenes has been reported (7,8,15), and different data from previous in vitro and animal studies and clinical practice suggest that AMB is not an effective option for invasive A. terreus infections (7,15,16,19). New treatment strategies, such as the use of expanded-spectrum triazoles like voriconazole (VRC) as a first-line treatment and posaconazole (PSC) as prophylaxis and salvage therapy, are recommended in clinical practice guidelines for invasive aspergillosis (18).…”

mentioning

confidence: 99%

In Vitro Activity and In Vivo Efficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of the Aspergillus terreus Complex

Salas

Pastor

Rodríguez

et al. 2011

Antimicrob Agents Chemother

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Posaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated the in vitro activity of PSC against 21 strains of the Aspergillus terreus complex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the two in vitro methods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.

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Antifungal Therapy of Murine Aspergillus terreus Infection

Cited by 39 publications

References 24 publications

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance

In Vitro Activity and In Vivo Efficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of the Aspergillus terreus Complex

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