scholarly journals In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against Candida auris

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1767
Author(s):  
Unai Caballero ◽  
Elena Eraso ◽  
Javier Pemán ◽  
Guillermo Quindós ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Simulation Analysis ◽  
Compartment Model ◽  
Resistance Rate ◽  
Modelling And Simulation ◽  
Candida Auris ◽  
Transfer Constant ◽  
Pharmacodynamic Modelling

The aims of this study were to characterize the antifungal activity of amphotericin B against Candida auris in a static in vitro system and to evaluate different dosing schedules and MIC scenarios by means of semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation. A two-compartment model consisting of a drug-susceptible and a drug-resistant subpopulation successfully characterized the time-kill data and a modified Emax sigmoidal model best described the effect of the drug. The model incorporated growth rate constants for both subpopulations, a death rate constant and a transfer constant between both compartments. Additionally, the model included a parameter to account for the delay in growth in the absence or presence of the drug. Amphotericin B displayed a concentration-dependent fungicidal activity. The developed PK/PD model was able to characterize properly the antifungal activity of amphotericin B against C. auris. Finally, simulation analysis revealed that none of the simulated standard dosing scenarios of 0.6, 1 and 1.5 mg/kg/day over a week treatment showed successful activity against C. auris infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for C. auris invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.

scholarly journals In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris

2021 ◽  
Author(s):  
Janet Herrada ◽  
Ahmed Gamal ◽  
Lisa Long ◽  
Sonia P. Sanchez ◽  
Thomas S. McCormick ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Kidney Tissue ◽  
Treated Group ◽  
Untreated Group ◽  
Candida Auris ◽  
Fungal Burden ◽  
In Vivo Antifungal Activity

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/mL, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg -treated group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data shows that AmBisome shows significant antifungal activity against C. auris in vitro as well as in vivo.

scholarly journals Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258465
Author(s):  
Mohamed Hagras ◽  
Nader S. Abutaleb ◽  
Ahmed M. Sayed ◽  
Ehab A. Salama ◽  
Mohamed N. Seleem ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Conformationally Restricted ◽  
Normal Human

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

scholarly journals Efficacy of Voriconazole, Isavuconazole, Fluconazole, and Anidulafungin in the treatment of emerging Candida auris using an immunocompromised murine model of disseminated candidiasis

2021 ◽  
Author(s):  
Ahmed Gamal ◽  
Lisa Long ◽  
Janet Herrada ◽  
Jalal Aram ◽  
Thomas S. McCormick ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Murine Model ◽  
Kidney Tissue ◽  
Comparable Efficacy ◽  
P Value ◽  
Candida Auris ◽  
Fungal Burden

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo . Minimum inhibitory concentrations (MICs) for Anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 μg/mL, respectively. Significant in vivo efficacy was observed in anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to the untreated group ( P-value of < 0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacy against C. auris , whereas isavuconazole did not show significant in vivo activity.

scholarly journals Antifungal Activity of Flocculosin, a Novel Glycolipid Isolated from Pseudozyma flocculosa

2005 ◽  
Vol 49 (4) ◽  
pp. 1597-1599 ◽  
Author(s):  
Benjamin Mimee ◽  
Caroline Labbé ◽  
René Pelletier ◽  
Richard R. Bélanger
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Cell Lines ◽  
Human Cell ◽  
Synergistic Activity ◽  
Human Cell Lines ◽  
Antifungal Properties ◽  
Pseudozyma Flocculosa ◽  
In Vitro Antifungal Activity

ABSTRACT Flocculosin, a glycolipid isolated from the yeast-like fungus Pseudozyma flocculosa, was investigated for in vitro antifungal activity. The compound displayed antifungal properties against several pathogenic yeasts. Synergistic activity was observed between flocculosin and amphotericin B, and no significant cytotoxicity was demonstrated when tested against human cell lines.

scholarly journals In Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No Antagonism

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui
Keyword(s):  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Resistant Mutants ◽  
Hospital Acquired

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

Amphotericin B in Lipid Emulsion: Stability, Compatibility, and In Vitro Antifungal Activity

1998 ◽  
Vol 42 (4) ◽  
pp. 762-766 ◽  
Author(s):  
Scott Walker ◽  
Sandra A. N. Tailor ◽  
Mark Lee ◽  
Lisa Louie ◽  
Marie Louie ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Clinical Laboratory ◽  
National Committee ◽  
Compatibility Study ◽  
The Stability ◽  
Few Data ◽  
Reference Strains ◽  
In Vitro Antifungal Activity

ABSTRACT Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23°C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.

In-Vitro and In-Vivo Studies on Novel Chitosan-g-Pluronic F-127 Copolymer Based Nanocarrier of Amphotericin B for Improved Antifungal Activity

2014 ◽  
Vol 4 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Vivek Kumar ◽  
Pramod K. Gupta ◽  
Vivek K. Pawar ◽  
Ashwni Verma ◽  
Renuka Khatik ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B

scholarly journals Amphotericin B-conjugated polypeptide hydrogels as a novel innovative strategy for fungal infections

2018 ◽  
Vol 5 (3) ◽  
pp. 171814 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Wen Yang ◽  
Duo Li ◽  
Shunli Ji ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Water Soluble ◽  
Naphthalene Acetic Acid ◽  
Innovative Strategy ◽  
Molecular Arrangement

The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans . The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.

scholarly journals Structure-Antifungal Activity Relationships of Polyene Antibiotics of the Amphotericin B Group

2013 ◽  
Vol 57 (8) ◽  
pp. 3815-3822 ◽  
Author(s):  
Anna N. Tevyashova ◽  
Evgenia N. Olsufyeva ◽  
Svetlana E. Solovieva ◽  
Svetlana S. Printsevskaya ◽  
Marina I. Reznikova ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Cooh Group ◽  
Hydroxyl Groups ◽  
Activity Data ◽  
Oh Groups ◽  
Polyene Antibiotics ◽  
High Antifungal Activity

ABSTRACTA comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics andin vitroantifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect thein vitroantifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were testedin vivoto determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely,N-(l-lysyl)-BSG005 (compound 3n) and, especially,l-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable inin vitroandin vivotests to AMB and that have better toxicological properties.

scholarly journals Evaluation of the In Vitro and In Vivo Antifungal Activity of APX001A/APX001 Against Candida auris

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S471-S472
Author(s):  
Emily Larkin ◽  
Lisa Long ◽  
Christopher Hager ◽  
Karen Joy Shaw ◽  
Mahmoud Ghannoum
Keyword(s):  
Antifungal Activity ◽  
Candida Auris ◽  
In Vivo Antifungal Activity
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