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 ◽  
...  

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.

1998 ◽  
Vol 42 (11) ◽  
pp. 3012-3013 ◽  
Author(s):  
C. Rimaroli ◽  
T. Bruzzese

ABSTRACT The in vitro activity of a new water-soluble polyene, SPA-S-843, was evaluated against 116 strains of Candida,Cryptococcus, and Saccharomyces spp. and compared with that of amphotericin B. SPA-S-843 demonstrated better inhibitory activity against all of the yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis than did amphotericin B.


1997 ◽  
Vol 41 (11) ◽  
pp. 2576-2578 ◽  
Author(s):  
J A Karlowsky ◽  
G A Harding ◽  
S A Zelenitsky ◽  
D J Hoban ◽  
A Kabani ◽  
...  

In vitro killing by a new semisynthetic echinocandin, LY-303366, was characterized using clinical isolates of fluconazole-sensitive (Y58) and -resistant (Y180) Candida albicans as well as Candida glabrata (Y7) and Candida krusei (Y171). The 24-h kill curves for Y58 and Y180 demonstrated dose-independent killing of between 1 and 2 log10 with LY-303366 at concentrations of 0.1, 1, 10, 50, 100, and 1,000 times the MIC. Regrowth did not occur at 24 h with either C. albicans isolate at the aforementioned LY-303366 concentrations. At their MICs, LY-303366 and amphotericin B produced similar killing kinetics in cultures of Y58, Y180, Y7, and Y171, while all cultures exposed to fluconazole at its MIC demonstrated stasis or growth over 24 h.


Author(s):  
Joachim Ohiakwu Ezeadila ◽  
Ikechukwu Okoli ◽  
Christie Amaechi Oyeka

There is an increase in non-albicans Candida (NAC) vulvovaginal candidiasis which is attributed to overuse of antifungal therapy and this has led to antifungal resistance. This study was aimed at determining the antifungal resistance pattern of some clinical isolates of Candida species. Eighty-eight (88) isolates were used which included Candida tropicalis (34), Candida Parapsilosis (21), Candida albicans (20), Candida krusei (7) and Candida glabrata (6). The drugs used were Fluconazole (25µg), Ketoconazole (10µg), Voriconazole (1µg), Nystatin (100Units), Amphotericin B (20µg), Flucytosine (1µg), Clotrimazole (10µg) and Itraconazole (50µg). The susceptibility testing was carried out using the M44-A standard method for yeast disk diffusion testing. Results showed that the percentages of Candida species resistant to Fluconazole, Ketoconazole, Voriconazole, Amphotericin B, Flucytosine, Clotrimazole and Itraconazole and Nystatin were 52.3%, 61.9%, 35.2%, 19.3%, 86.4%, 34.1%,  45.5% and 44.3%,  with inhibition zone diameters ≤14mm, ≤20mm, ≤13mm, <10mm, ≤11mm, ≤11mm, ≤13mm and no inhibition zone diameter respectively. Candida krusei was the most resistant species with 100% resistance to each of Fluconazole, Ketoconazole and Flucytosine. Candida tropicalis was the species with the highest susceptibility (79.4%) to Amphotericin B followed by Candida parapsilosis with inhibition zone diameters ≥15mm. While Candida glabrata showed 100% resistance to each of Flucytosine and Itraconazole, Candida albicans showed 100% resistance to Flucytosine only. Candida glabrata was the only Candida species with 0% resistance to Amphotericin B. The drug to which most of the Candida species were susceptible was Amphotericin B followed by Voriconazole while Flucytosine was the drug with the highest resistance followed by Ketoconazole and Fluconazole. The highest number of susceptible-dose dependent Candida isolates was observed with Ketoconazole (25%), followed by Clotrimazole and Itraconazole, each recording 23.9%. Based on the findings of the present study, Voriconazole is recommended for vaginal candidiasis especially in the study area and also especially for infections caused by Fluconazole-resistant Candida species. This suggests that routine sensitivity testing is pertinent to guiding the choice of antifungal therapy. Thus, indiscriminate use of antifungal drugs should be avoided to reduce the development and spread of resistance.


1994 ◽  
Vol 59 (11) ◽  
pp. 2562-2564 ◽  
Author(s):  
Martin Doležal ◽  
Jiří Hartl ◽  
Miloš Macháček

During the course of a search for new antimycotic agents a series of 3-amino-5-cyano-2-pyrazinecarboxamides I - XI have been synthesized. The prepared compounds were tested for their antimycotic activity. The MIC of these in the form of dimethyl sulfoxide solutions was measured against Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E28, Candida glabrata 20/I, Trichosporon beigelii 1188, Trichophyton mentagrophytes 445, Aspergillus fumigatus 231, and Absidia corymbifera 272. None of the compounds studied was particularly effective.


2001 ◽  
Vol 45 (6) ◽  
pp. 1905-1907 ◽  
Author(s):  
Manuel Cuenca-Estrella ◽  
Emilia Mellado ◽  
Teresa M. Dı́az-Guerra ◽  
Araceli Monzón ◽  
Juan L. Rodrı́guez-Tudela

ABSTRACT The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candidaspp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreased susceptibility to azoles. Candida krusei, Candida parapsilosis, Candida lusitaniae, and Candida guilliermondii are resistant to GW 471558 in vitro (MICs, >128 μg/ml).


2008 ◽  
Vol 52 (5) ◽  
pp. 1884-1887 ◽  
Author(s):  
Rawya S. Al-Dhaheri ◽  
L. Julia Douglas

ABSTRACT Biofilms and planktonic cells of five Candida species were surveyed for the presence of persister (drug-tolerant) cell populations after exposure to amphotericin B. None of the planktonic cultures (exponential or stationary phase) contained persister cells. However, persisters were found in biofilms of one of two strains of Candida albicans tested and in biofilms of Candida krusei and Candida parapsilosis, but not in biofilms of Candida glabrata or Candida tropicalis. These results suggest that persister cells cannot solely account for drug resistance in Candida biofilms.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  

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.


2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.


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