scholarly journals A comparative study of the post-antifungal effect (PAFE) of amphotericin B, triazoles and echinocandins on Aspergillus fumigatus and Candida albicans

2004 ◽  
Vol 53 (2) ◽  
pp. 386-389 ◽  
Author(s):  
E. K. Manavathu
Keyword(s):  
Candida Albicans ◽  
Comparative Study ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Antifungal Effect

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals A comparative study of fungicidal activities of voriconazole and amphotericin B against hyphae of Aspergillus fumigatus

2005 ◽  
Vol 55 (6) ◽  
pp. 914-920 ◽  
Author(s):  
Suganthini Krishnan ◽  
Elias K. Manavathu ◽  
Pranatharthi H. Chandrasekar
Keyword(s):  
Comparative Study ◽  
Aspergillus Fumigatus ◽  
Amphotericin B

scholarly journals Organism-Dependent Fungicidal Activities of Azoles

1998 ◽  
Vol 42 (11) ◽  
pp. 3018-3021 ◽  
Author(s):  
Elias K. Manavathu ◽  
Jessica L. Cutright ◽  
Pranatharthi H. Chandrasekar
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
The Other ◽  
Cellular Death ◽  
Antifungal Activities ◽  
Other Hand ◽  
Cytocidal Effect ◽  
Time Kill ◽  
Drug Free

ABSTRACT We investigated the antifungal activities of itraconazole and voriconazole on Aspergillus species by time kill studies, and the results were compared with those obtained forCandida species. Exposure of Aspergillus fumigatus conidia to varying concentrations (1.25 to 10 μg/ml) of itraconazole and voriconazole resulted in cellular death; the cytocidal effect was time and concentration dependent. In contrast, no killing of Candida albicans occurred in the presence of itraconazole and voriconazole at concentrations as high as 10 μg/ml, although candidal growth was inhibited compared to the drug-free control. Amphotericin B (1.25 to 10 μg/ml), on the other hand, killed both A. fumigatus and C. albicans. Similar results were obtained for non-A. fumigatus aspergilli and non-C. albicans Candida species. These observations indicate that both itraconazole and voriconazole are cytocidal agents for Aspergillus species but not for Candidaspecies, suggesting that azoles possess organism-dependent fungicidal activities.

scholarly journals Amphotericin B- and Fluconazole-ResistantCandida spp., Aspergillus fumigatus, and Other Newly Emerging Pathogenic Fungi Are Susceptible to Basic Antifungal Peptides

1999 ◽  
Vol 43 (3) ◽  
pp. 702-704 ◽  
Author(s):  
Eva J. Helmerhorst ◽  
Ingrid M. Reijnders ◽  
Wim van ’t Hof ◽  
Ina Simoons-Smit ◽  
Enno C. I. Veerman ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Candida Glabrata ◽  
Frog Skin ◽  
Pathogenic Fungi ◽  
Candida Krusei ◽  
Histatin 5 ◽  
Antifungal Peptides ◽  
Fluconazole Resistant

ABSTRACT The present study shows that a number of basic antifungal peptides, including human salivary histatin 5, a designed histatin analog designated dhvar4, and a peptide from frog skin, PGLa, are active against amphotericin B-resistant Candida albicans,Candida krusei, and Aspergillus fumigatusstrains and against a fluconazole-resistant Candida glabrata isolate.

Amphotericin B-Associated Hypertension

1996 ◽  
Vol 30 (7-8) ◽  
pp. 765-767 ◽  
Author(s):  
Ysa Le ◽  
Khurram Z Rana ◽  
Michael N Dudley
Keyword(s):  
Blood Pressure ◽  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Causal Relationship ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Acute Hypertension ◽  
Case Summary ◽  
Para Determinar

OBJECTIVE: To report two cases of hypertension related to amphotericin B infusion. CASE SUMMARY: A 63-year-old woman with Candida albicans bacteremia and an 84-year-old man with Aspergillus fumigatus pneumonia developed hypertension within minutes of amphotericin B administration. Both patients' blood pressure returned to baseline soon after the infusion of amphotericin B was stopped. Neither patient was rechallenged. DISCUSSION: A causal relationship may exist between the administration of amphotericin B and these hypertensive episodes. Blood pressure in both patients normalized without treatment on discontinuation of the infusion. The mechanism of amphotericin B-associated hypertension is unclear but could include vasoconstricting properties of the drug or the administration of intravenous NaCl 0.9% prior to amphotericin B infusion. We recommend that intravenous NaCl 0.9% be administered following amphotericin B infusion and that the infusion be stopped if hypertensive episodes arise. CONCLUSIONS: Both acute hypertension and hypotension can occur in patients receiving amphotericin B for systemic fungal infections. OBJETIVO: Reportar dos casos de hipertensión relacionados a la infusión de anfotericina B. RESUMEN DEL CASO: Una paciente de 63 años de edad con bacteremia debida a la Candida albicans y un paciente de 84 años de edad con neumonía debida al Aspergillus fumigatus desarrollaron hipertensión a los pocos minutos de comenzar la administración de anfotericina B. La presión sanguínea de ambos pacientes retornó a la línea de base tan pronto como se detuvo la infusión de anfortericina B. Ninguno de los dos pacientes fue reexpuesto a la anfotericina B para determinar si el evento se repeatía. DISCUSIÓN: Puede existir una relación causal entre la adminstración de anfotericina B y estos episodios de hipertensión reportados, ya que la presión sanguínea se normalizó en ambos pacientes sin necesidad de tratamiento adicional después de que se suspendió la infusión de anfotericina B. El mecanismo por el cual anfotericina está asociada al desarrollo de hipertensión no está claro pero se especula que se debe a las propiedades vasoconstrictoras del medicamento o a la administración de cloruro de sodio intravenosamente antes de comenzar la infusión de anfotericina B. Por consiguiente, los autores recomiendan que el cloruro de sodio sea administrado después de que se haya concluido la infusión de anfotericina B. En el caso de que se reporten episodios hipertensivos, la infusión de anfotericina B debería ser suspendida inmediatamente. CONCLUSIONES: Casos de hipertensión o hipotensión pueden ocurrir en pacientes que reciben anfotericina B para el tratamiento de infecciones fungosas sistémicas.

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