Antifungal drug resistance to azoles and polyenes

Canuto, Mar Masiá; Rodero, Félix Gutiérrez

doi:10.1016/s1473-3099(02)00371-7

Cited by 273 publications

(133 citation statements)

References 161 publications

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“…With the advent of fungal isolates manifesting resistance to azole and polyene drugs (Canuto & Rodero, 2002) there is a requirement for new drugs with alternative modes of action or with the ability to increase the efficacy of existing prescription drugs. Many metalbased drugs display modes of action distinct to those of the prescription anti-fungals (Coyle et al 2003a) possibly allowing their use where resistance to conventional drugs has emerged (White et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Conventional therapies for the control of these diseases rely upon the use of azole and polyene drugs which target ergosterol biosynthesis and alter membrane permeability, respectively (White et al, 1998, Abu Salah, 1996. In recent years, the appearance of fungal strains manifesting resistance to conventional drugs (Canuto & Rodero, 2002) has prompted the search for novel anti-fungals with modes of action distinct to the existing range of anti-fungals.…”

Section: Introductionmentioning

confidence: 99%

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Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Eshwika

Coyle

Devereux³

et al. 2004

Biometals

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Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO 4 ) 2 · 6H 2 O and [Cu(phendio) 3 ](ClO 4 ) 2 · 4H 2 O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC 90 whereas pre-growth in AgClO 4 and [Ag(phendio) 2 ]ClO 4 resulted in a small decrease in the relevant MIC 90 values. The copper complexes reduce the oxygen consumption of C. albicans while the silver complexes increase oxygen consumption. In addition, pregrowth of cells in the copper complexes resulted in a lower ergosterol content while the silver complexes induced an elevation in ergosterol synthesis.The ability of copper and silver complexes to alter the susceptibility of C. albicans to miconazole and amphotericin B may be influenced by their action on respiration, since reduced respiration rates correlate with reduced cellular ergosterol which is the target for amphotericin B. Lower levels of ergosterol have previously been associated with elevated tolerance to this drug. In the case of reduced sensitivity to miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise to fewer toxic side products once biosynthesis is inhibited by miconazole.Abbreviations: phendio = 1,10-phenanthroline-5,6-dione. phen = 1,10-phenanthroline

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Eshwika

Coyle

Devereux³

et al. 2004

Biometals

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“…La buena evolucion con Anfotericina B liposomal en este cuadro, seguida de Itraconazol creemos que es una experiencia útil a comentar, dada la escasez de casos de esta infección que han sobrevivido con esta pauta, y la falta de una pauta idónea por definir en la infección por Aspergillus spp. (11,12).…”

Section: Discussionunclassified

Infección invasiva por Aspergillus terreus tratada con éxito con anfotericina B liposomal

Ortega

Navas

González

et al. 2004

An. Med. Interna (Madrid)

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La infección por Aspergillus spp. es típica de pacientes inmunodeprimidos (1-4). De las distintas especies patógenas conocidas de aspergillus para la especie humana la infección por Aspergillus terreus es poco frecuente, y, habitualmente se asocia a estancias en las unidades de medicina intensiva. En una revisión reciente publicada en la más prestigiosa revista de enfermedades infecciosas se comparan 11 casos de aspergilosis invasiva por Aspergillus terreus diagnosticados en los últimos 12 años con otros 19 casos encontrados en la literatura. La mortalidad de los pacientes de la institución fue de 10 de los 11 pacientes (5). En el presente caso se trata de una mujer anciana con colagenosis tratada con esteroides que se presentó con infiltrados en ambos pulmones y una dudosa discitis vertebral y que fue diagnosticada de aspergilosis pulmonar invasiva en base a histología compatible y cultivo de Aspergillus terreus en el broncoaspirado. Con tratamiento prolongado con anfotericina B liposomal seguido de itraconazol, experimentó mejoría progresiva hasta la curación, permaneciendo asintomática al año de retirar el tratamiento antimicótico. [0212-7199 (2004) RESUMENUna mujer de 75 años ingresó en nuestro hospital para evaluación de debilidad en miembros inferiores y deterioro. Se detectaron múltiples fracturas vertebrales por aplastamiento, con dudosa discitis, una lesión cavitada en lóbulo superior derecho y otro infiltrado en lóbulo superior izquierdo, observándose en la PAAF de la lesión cavitada un hongo filamentoso y siendo el cultivo del broncoaspirado positivo para Aspergillus terreus. Con tratamiento prolongado con anfotericina B liposomal desapareció la lesión, permaneciendo posteriormente con itraconazol oral 3 meses. Los datos clínicos y analíticos demuestran la existencia de una colagenosis tipo síndrome Overlap, con criterios de síndrome antifosfolí-pido secundario. Se comenta la rareza de la infección por Aspergillus terreus en pacientes que no han ingresado en Medicina Intensiva y la buena respuesta al tratamiento con anfotericina B liposomal, que contrasta con la elevada mortalidad referida en una revisión reciente. Otros aspectos a comentar son la coexistencia con una colagenosis y un síndro-me antifosfolípido secundario con los títulos más elevados de ACA IgM que hemos encontrado en la literatura.

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“…Voriconazole, for instance, is an azole whose antifungal spectrum is broader than fluconazole, with a potency 10 to 100 times greater against Candida species [7,8]. However, C. glabrata has rapidly developed resistance to voriconazole and other later generation azoles, presenting with higher MICs than those seen for most C. albicans isolates [6].…”

Section: Introductionmentioning

confidence: 99%

Biguanides enhance antifungal activity against Candida glabrata

Feliu

Lord

et al. 2018

Virulence

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Candida spp. are the fourth leading cause of nosocomial blood stream infections in North America. Candida glabrata is the second most frequently isolated species, and rapid development of antifungal resistance has made treatment a challenge. In this study, we investigate the therapeutic potential of metformin, a biguanide with well-established action for diabetes, as an antifungal agent against C. glabrata. Both wild type and antifungal-resistant isolates of C. glabrata were subjected to biguanide and biguanide-antifungal combination treatment. Metformin, as well as other members of the biguanide family, were found to have antifungal activity against C. glabrata, with MIC50 of 9.34 ± 0.16 mg/mL, 2.09 ± 0.04 mg/mL and 1.87 ± 0.05 mg/mL for metformin, phenformin and buformin, respectively. We demonstrate that biguanides enhance the activity of several antifungal drugs, including voriconazole, fluconazole, and amphotericin, but not micafungin. The biguanide-antifungal combinations allowed for additional antifungal effects, with fraction inhibition concentration indexes ranging from 0.5 to 1. Furthermore, metformin was able to lower antifungal MIC50 in voriconazole and fluconazole-resistant clinical isolates of C. glabrata. We also observed growth reduction of C. glabrata with rapamycin and an FIC of 0.84 ± 0.09 when combined with metformin, suggesting biguanide action in C. glabrata may be related to inhibition of the mTOR complex. We conclude that the biguanide class has direct antifungal therapeutic potential and enhances the activity of select antifungals in the treatment of resistant C. glabrata isolates. These data support the further investigation of biguanides in the combination treatment of serious fungal infections.

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Antifungal drug resistance to azoles and polyenes

Cited by 273 publications

References 161 publications

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Infección invasiva por Aspergillus terreus tratada con éxito con anfotericina B liposomal

Biguanides enhance antifungal activity against Candida glabrata

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