In vitro interactions of licensed and novel antifungal drugs against Fusarium spp

Ortoneda, Montserrat; Capilla, Javier; Pastor, Francisco; Pujol, Isabel; Guarro, Josep

doi:10.1016/j.diagmicrobio.2003.09.003

Cited by 48 publications

(40 citation statements)

References 16 publications

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“…In general, the differences among the MICs of the molecular clades, determined by using the Mann-Whitney U test (P Ͻ 0.05), were not statistically significant, with the exception of those for ketoconazole and ravuconazole, which showed less activity against the isolates of (6,19,21). In a previous in vitro study, terbinafine combined with different azoles, such as albaconazole, ravuconazole, and voriconazole, showed synergistic activity against the three isolates of F. verticillioides that were tested (17). No data exists on the clinical use of terbinafine to treat infections by F. verticillioides.…”

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confidence: 99%

In Vitro Antifungal Susceptibility and Molecular Characterization of Clinical Isolates of Fusarium verticillioides ( F. moniliforme ) and Fusarium thapsinum

Azor

Gené

Cano

et al. 2008

Antimicrob Agents Chemother

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confidence: 99%

In Vitro Antifungal Susceptibility and Molecular Characterization of Clinical Isolates of Fusarium verticillioides ( F. moniliforme ) and Fusarium thapsinum

Azor

Gené

Cano

et al. 2008

Antimicrob Agents Chemother

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“…The potent in vitro synergy observed between terbinafine and azole antifungals for a wide range of fungal pathogens enhances the potential role of terbinafine in the treatment of refractory IFIs (6)(7)(8)(9)(10)(11). The complementary mechanisms of action of terbinafine and azoles, which inhibit squalene epoxidase and lanosterol 14␣-demethylase, respectively, theoretically result in dual inhibition of fungal ergosterol production (29).…”

Section: Discussionmentioning

confidence: 99%

“…Due to its broad antifungal spectrum, interest in terbinafine has expanded to include its use in a range of cutaneous and subcutaneous mycoses, such as sporotrichosis, eumycetoma, and chromoblastomycosis (2-4), as well as in combination with other antifungal agents to treat resistant or refractory invasive fungal infections (IFIs), as described in numerous case reports (1,5). In support of the latter indication, synergistic in vitro antifungal activity has been demonstrated with terbinafine in combination with azole antifungals for many important fungal pathogens, including Aspergillus spp., zygomycetes, Fusarium spp., Paecilomyces spp., Candida albicans, dematiaceous molds, and the highly resistant Scedosporium prolificans (6)(7)(8)(9)(10)(11).…”

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Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

Dolton

Perera

Pont

et al. 2014

Antimicrob Agents Chemother

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dTerbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of highdose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (C max ), and minimum concentration (C min ) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.T he allylamine antifungal terbinafine is a well-established agent in the treatment of onychomycosis (1). Due to its broad antifungal spectrum, interest in terbinafine has expanded to include its use in a range of cutaneous and subcutaneous mycoses, such as sporotrichosis, eumycetoma, and chromoblastomycosis (2-4), as well as in combination with other antifungal agents to treat resistant or refractory invasive fungal infections (IFIs), as described in numerous case reports (1, 5). In support of the latter indication, synergistic in vitro antifungal activity has been demonstrated with terbinafine in combination with azole antifungals for many important fungal pathogens, including Aspergillus spp., zygomycetes, Fusarium spp., Paecilomyces spp., Candida albicans, dematiaceous molds, and the highly resistant Scedosporium prolificans (6-11).High dose is a consistent feature of terbinafine use in these indications, with daily doses of up to 1,000 mg daily (1) used to boost the plasma concentrations of terbinafine, which are known to be low following standard dosing, such as the standard dosing regimen of 250 mg daily in onychomycosis, due to extensive accumulation in skin and adipose tissue (12). However, no studies have assessed the systemic exposure of higher-dose terbinafine treatment (Ͼ250 mg daily) or divided daily doses (every 12 h [q12h] or q8h), factors that are likely to be crucial to the utility of terbinafine in effectively treating systemic mycoses in combination with other antifungals. This pauci...

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“…Fusarium spp. are opportunistic filamentous fungi widely distributed in soil, water, plants, and other organic substrates (Ortoneda et al, 2004;Nucci and Anaissie, 2007). In immunocompromised humans, a few species of Fusarium can cause superficial or disseminated infection (Nucci and Anaissie, 2007).…”

Section: Introductionmentioning

confidence: 99%

Dermatitis in Captive Wyoming Toads (Bufo Baxteri) Associated With Fusarium Spp.

Perpiñán¹,

Trupkiewicz²,

Armbrust

et al. 2010

Journal of Wildlife Diseases

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of 49 Wyoming toads (Bufo baxteri) kept at Omaha's Henry Doorly Zoo (Nebraska, USA) died showing clinical signs of ventral erythema, inappetance, lethargy, and delayed righting reflex. Treatment with antifungals and antibiotics was unsuccessful in all cases. Histopathologic analyses revealed dermatitis as the primary problem in 20 of 21 toads in which skin was examined. Fungal dermatitis was present in 17 toads, with hyphae approximately 1-3 mm in diameter, and parallel cell walls and frequent septations. In 14 animals, the fungal dermatitis was the main pathologic lesion. Several species of bacteria were associated with all cases. A few animals tested positive for Ranavirus using polymerase chain reaction. Fusarium sp. was consistently cultured from skin, feces, kidneys, and from powdered food provided to crickets. Four isolates were identified as Fusarium proliferatum, Fusarium oxysporum, Fusarium solani, and Fusarium verticillioides, which suggested a secondary role of fungi. A specific underlying cause of disease could not be found, although the roles of humidity and Ranavirus infection are discussed, along with the well-known susceptibility of bufonids to fungal dermatitis.

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In vitro interactions of licensed and novel antifungal drugs against Fusarium spp

Cited by 48 publications

References 16 publications

In Vitro Antifungal Susceptibility and Molecular Characterization of Clinical Isolates of Fusarium verticillioides ( F. moniliforme ) and Fusarium thapsinum

In Vitro Antifungal Susceptibility and Molecular Characterization of Clinical Isolates of Fusarium verticillioides ( F. moniliforme ) and Fusarium thapsinum

Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

Dermatitis in Captive Wyoming Toads (Bufo Baxteri) Associated With Fusarium Spp.

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