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 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 Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

2000 ◽  
Vol 44 (11) ◽  
pp. 2932-2938 ◽  
Author(s):  
O. Marchetti ◽  
J. M. Entenza ◽  
D. Sanglard ◽  
J. Bille ◽  
M. P. Glauser ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Cyclosporine A ◽  
Test Organism ◽  
The Other ◽  
High Dose ◽  
Therapeutic Results ◽  
Fluconazole Therapy ◽  
High Doses

ABSTRACT Recent observations demonstrated that fluconazole plus cyclosporine (Cy) synergistically killed Candida albicans in vitro. This combination was tested in rats with C. albicansexperimental endocarditis. The MICs of fluconazole and Cy for the test organism were 0.25 and >10 mg/liter, respectively. Rats were treated for 5 days with either Cy, amphotericin B, fluconazole, or fluconazole-Cy. Although used at high doses, the peak concentrations of fluconazole in the serum of rats (up to 4.5 mg/liter) were compatible with high-dose fluconazole therapy in humans. On the other hand, Cy concentrations in serum (up to 4.5 mg/liter) were greater than recommended therapeutic levels. Untreated rats demonstrated massive pseudohyphal growth in both the vegetations and the kidneys. However, only the kidneys displayed concomitant polymorphonuclear infiltration. The therapeutic results reflected this dissociation. In the vegetations, only the fungicidal fluconazole-Cy combination significantly decreased fungal densities compared to all groups, including amphotericin B (P < 0.0001). In the kidneys, all regimens except the Cy regimen were effective, but fluconazole-Cy remained superior to amphotericin B and fluconazole alone in sterilizing the organs (P < 0.0001). While the mechanism responsible for the fluconazole-Cy interaction is hypothetical, this observation opens new perspectives for fungicidal combinations between azoles and other drugs.

scholarly journals In VitroInteraction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

2012 ◽  
Vol 57 (3) ◽  
pp. 1275-1282 ◽  
Author(s):  
Francesca Bugli ◽  
Brunella Posteraro ◽  
Massimiliano Papi ◽  
Riccardo Torelli ◽  
Alessandro Maiorana ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Extracellular Polymeric Substances ◽  
Alginate Lyase ◽  
Antifungal Drugs ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Time Kill

ABSTRACTAspergillus fumigatusbiofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treatAspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study,in vitrointeractions between polyene antifungals (AMB and LAMB) and alginate lyase (AlgL), an enzyme degrading the polysaccharides produced as extracellular polymeric substances (EPSs) within the biofilm matrix, againstA. fumigatusbiofilms were evaluated by using the checkerboard microdilution and the time-kill assays. Furthermore, atomic force microscopy (AFM) was used to image and quantify the effects of AlgL-antifungal combinations on biofilm-growing hyphal cells. On the basis of fractional inhibitory concentration index values, synergy was found between both AMB formulations and AlgL, and this finding was also confirmed by the time-kill test. Finally, AFM analysis showed that whenA. fumigatusbiofilms were treated with AlgL or polyene alone, as well as with their combination, both a reduction of hyphal thicknesses and an increase of adhesive forces were observed compared to the findings for untreated controls, probably owing to the different action by the enzyme or the antifungal compounds. Interestingly, marked physical changes were noticed inA. fumigatusbiofilms exposed to the AlgL-antifungal combinations compared with the physical characteristics detected after exposure to the antifungals alone, indicating that AlgL may enhance the antibiofilm activity of both AMB and LAMB, perhaps by disrupting the hypha-embedding EPSs and thus facilitating the drugs to reach biofilm cells. Taken together, our results suggest that a combination of AlgL and a polyene antifungal may prove to be a new therapeutic strategy for invasive aspergillosis, while reinforcing the EPS as a valuable antibiofilm drug target.

Microbial Hydroxylation of Hydroxyprogesterones and α-Glucosidase Inhibition Activity of Their Metabolites

2007 ◽  
Vol 62 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Muhammad Iqbal Choudhary ◽  
Muhammad Nasir ◽  
Shamsun N. Khan ◽  
Muhammad Atif ◽  
Rahat A. Ali ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Activity ◽  
Microbial Transformation ◽  
The Other ◽  
Gibberella Fujikuroi ◽  
Spectroscopic Methods ◽  
Cunninghamella Elegans ◽  
Inhibition Activity ◽  
Microbial Hydroxylation ◽  
Other Hand

Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella fujikuroi, Fusarium lini, and Candida albicans yielded 11α,15α,16α-trihydroxypregn-4- ene-3,20-dione (3), 11α-hydroxy-5α-pregnane-3,20-dione (4), 6β ,11α-dihydroxypregn-4-ene-3,20- dione (5), 11α-hydroxypregna-1,4-diene-3,20-dione (6), 11α,17β -dihydroxyandrost-4-en-3-one (7), and 11α,15α-dihydroxypregn-4-ene-3,20-dione (8). On the other hand, microbial transformation of 17α-hydroxyprogesterone (2) with Cunninghamella elegans and Fusarium lini yielded 11α,17α- dihydroxypregn-4-ene-3,20-dione (9), and 17α-hydroxypregna-1,4-diene-3,20-dione (10). The structures of the metabolites 3 - 10 were deduced on the basis of spectroscopic methods. Compound 3 was identified as a new metabolite, which exhibited a promising inhibitory activity against the α-glucosidase enzyme.

scholarly journals In Vitro Pharmacodynamic Properties of Three Antifungal Agents against Preformed Candida albicans Biofilms Determined by Time-Kill Studies

2002 ◽  
Vol 46 (11) ◽  
pp. 3634-3636 ◽  
Author(s):  
Gordon Ramage ◽  
Kacy VandeWalle ◽  
Stefano P. Bachmann ◽  
Brian L. Wickes ◽  
José L. López-Ribot
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Pharmacokinetic Properties ◽  
Time Kill ◽  
Candida Albicans Biofilms

ABSTRACT We have examined the in vitro activities of fluconazole, amphotericin B, and caspofungin against Candida albicans biofilms by time-kill methodology. Fluconazole was ineffective against biofilms. Killing of biofilm cells was suboptimal at therapeutic concentrations of amphotericin B. Caspofungin displayed the most effective pharmacokinetic properties, with ≥99% killing at physiological concentrations.

scholarly journals Synthesis and Antimicrobial Activity of 7-Hydroxy-3',4'-Methylenedioxy- and 7-Benzyloxy-3',4'-Methylenedioxy Flavanones

2017 ◽  
Vol 9 (3) ◽  
pp. 297-306 ◽  
Author(s):  
R. Ali ◽  
A. Rahim ◽  
A. Islam
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Elemental Analysis ◽  
The Other ◽  
Antifungal Activities ◽  
Fungal Strains ◽  
Antibacterial And Antifungal Activities ◽  
Other Hand ◽  
Antibacterial And Antifungal

7-Hydroxy-3',4'-methylenedioxy- and 7-benzyloxy-3',4'-methylenedioxy flavanones have been synthesized starting from 2,4-dihydroxyacetophenone. Subsequently biocidal activities of the flavanones have been investigated along with their corresponding chalcones against some bacterial and fungal strains. 2'-Hydroxy-4'-benzyloxy-3,4-methylenedioxy chalcone (5) and its corresponding flavanone (7) showed good antibacterial and antifungal activities against some selected bacterial and fungal strains. On the other hand, 2',4'-dihydroxy-3,4-methylenedioxy chalcone (4) showed no antibacterial and antifungal activities while its corresponding flavanone (6) showed a little antibacterial activity only at higher concentration but did not show antifungal activity. The synthesized chalcones and flavanones have been characterized using UV-Vis, IR and 1H NMRspectral data together with elemental analysis.

scholarly journals Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans.

1997 ◽  
Vol 41 (6) ◽  
pp. 1392-1395 ◽  
Author(s):  
M E Klepser ◽  
E J Wolfe ◽  
R N Jones ◽  
C H Nightingale ◽  
M A Pfaller
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Fungicidal Activity ◽  
Narrow Range ◽  
Growth Effects ◽  
Fungistatic Activity ◽  
Time Kill

Time-kill curves were determined for three isolates of Candida albicans tested against fluconazole and amphotericin B at multiples of the MIC. Fluconazole produced fungistatic activity, with concentration-related growth effects observed over a narrow range of concentrations. Amphotericin B exhibited fungicidal activity, with enhancement of activity over a broader range of concentrations.

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.

scholarly journals Synergistic Effect of Ceftazidime-Avibactam with Meropenem against Panresistant, Carbapenemase-Harboring Acinetobacter baumannii and Serratia marcescens Investigated Using Time-Kill and Disk Approximation Assays

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Juliana Januário Gaudereto ◽  
Lauro Vieira Perdigão Neto ◽  
Gleice Cristina Leite ◽  
Roberta Ruedas Martins ◽  
Gladys Villas Boas do Prado ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Serratia Marcescens ◽  
Acinetobacter Baumannii ◽  
The Other ◽  
Approximation Technique ◽  
Good Sensitivity ◽  
Content Type ◽  
Other Hand ◽  
Time Kill

ABSTRACT Susceptibility of ceftazidime-avibactam and in vitro synergy with meropenem were investigated using disk approximation and time-kill assays against 11 multiresistant Acinetobacter baumannii isolates harboring oxacillinases and 5 Serratia marcescens isolates carrying blaKPC-2. Ceftazidime-avibactam was very active and synergistic with meropenem against multiresistant S. marcescens isolates. On the other hand, only the A. baumannii isolates coharboring blaOXA-23 and blaOXA-117 displayed synergy. The disk approximation technique presented good sensitivity for synergism in S. marcescens infection.

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