scholarly journals Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus

2008 ◽  
Vol 63 (2) ◽  
pp. 343-348 ◽  
Author(s):  
T. Stergiopoulou ◽  
J. Meletiadis ◽  
T. Sein ◽  
P. Papaioannidou ◽  
I. Tsiouris ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Antifungal Agents ◽  
Interaction Analysis ◽  
Pharmacodynamic Interaction

scholarly journals Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus

2008 ◽  
Vol 52 (6) ◽  
pp. 2196-2204 ◽  
Author(s):  
Theodouli Stergiopoulou ◽  
Joseph Meletiadis ◽  
Tin Sein ◽  
Paraskevi Papaioannidou ◽  
Ioannis Tsiouris ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Topoisomerase Ii ◽  
Antibacterial Agents ◽  
Antifungal Agents ◽  
Management Strategies ◽  
Isobolographic Analysis ◽  
Pharmacodynamic Interactions ◽  
In Vitro Interaction

ABSTRACT Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 μg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus. Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis.

scholarly journals Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment

2003 ◽  
Vol 47 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Robert S. Liao ◽  
Robert P. Rennie ◽  
James A. Talbot
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Sybr Green ◽  
Sequential Treatment ◽  
Tetrazolium Salt ◽  
Fungal Cell ◽  
Sublethal Injury

ABSTRACT Amphotericin B treatment was previously shown to inhibit Candida albicans reproduction and reduce the fluorescence of vitality-specific dyes without causing a corresponding increase in the fluorescence of the mortality-specific dyes bis-(1,3-dibutylbarbituric acid)trimethine oxonol and SYBR Green Ι. In the present study, we have confirmed these results and have shown that the numbers of CFU are reduced by 99.9% by treatment with 0.5 μg of amphotericin B per ml for 10 h at 35°C. This reduction was not due to fungal cell death. First, the level of reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide increased in the presence of concentrations of amphotericin B that caused greater than 90% reductions in the numbers of CFU. Second, fungal cells treated with amphotericin B at a concentration of 0.5 μg/ml were resuscitated by further incubation at 22°C for 15 h in the continued presence of amphotericin B. Third, recovery of the ability to replicate was prevented by sequential treatment with 20 μg of miconazole per ml, which also increased the fluorescence of mortality-specific dyes to near the maximal levels achieved with 0.9 μg of amphotericin B per ml. Sequential treatment with fluconazole and flucytosine did not increase the levels of staining with the mortality-specific dyes. Itraconazole was less effective than ketoconazole, which was less effective than miconazole. The practice of equating the loss of the capacity of C. albicans to form colonies with fungal cell death may give incorrect results in assays with amphotericin B, and the results of assays with caution with other antifungal agents that are lipophilic or that possess significant postantifungal effects may need to be interpreted.

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 Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alice C. Copsey ◽  
Mario R. O. Barsottini ◽  
Benjamin May ◽  
Fei Xu ◽  
Mary S. Albury ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Future Development ◽  
Therapeutic Target ◽  
Fungicide Resistance ◽  
Alternative Oxidase ◽  
Antifungal Agents ◽  
Candida Auris ◽  
Novel Treatments ◽  
Membrane Bound ◽  
Self Assembled

AbstractCandidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (Km and Vmax) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.

scholarly journals CaNdt80 Is Involved in Drug Resistance in Candida albicans by Regulating CDR1

2004 ◽  
Vol 48 (12) ◽  
pp. 4505-4512 ◽  
Author(s):  
Chia-Geun Chen ◽  
Yun-Liang Yang ◽  
Hsin-I Shih ◽  
Chia-Li Su ◽  
Hsiu-Jung Lo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Type Strain ◽  
Antifungal Agents ◽  
Wild Type Strain ◽  
Efflux Pump ◽  
Antifungal Drugs ◽  
Galactosidase Activity ◽  
Wild Type

ABSTRACT Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80, increases the β-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.

Uses the Disinfectants against fungi isolated from the homes

2011 ◽  
Vol 35 (1) ◽  
pp. 167-173
Author(s):  
Rusol Muhammedi Al Bahran
Keyword(s):  
Candida Albicans ◽  
Statistical Analysis ◽  
Aspergillus Niger ◽  
Aspergillus Fumigatus ◽  
Sodium Hypochlorite ◽  
Frequency Ratio ◽  
Sensitivity Test ◽  
Common Genus

The study included 100 samples collected from different locations of the homes were located in the area of Ali Saleh in Baghdad 6 species were isolated from fungi and the most common genus or species of fungi isolated were Aspergillus fumigatus by frequency ratio of 25.84%, and occurrence ratio of 23%, Penicilium by frequency ratio of 21.34%, and occurrence ratio of 19%, Mucor by frequency ratio 20.22%, and the occurrence ratio of 18%, Candida albicans by frequency ratio of 15.73%, the occurrence ratio of 14%, Rhizopus frequency ratio by 13.48%, the occurrence ratio of 12% and Aspergillus niger frequency ratio by 3.37% and the occurrence ratio of 3%. Then the sensitivity test of disinfectants were studied against fungi isolated by using three disinfectants Chloroxylenol known commercially by (Dettol), Chlorhexidine commercially known by (Hibitane) and Sodium hypochlorite commercially known by (Bleach), and a study for the effected of three concentrations of each disinfectant (5, 2.5, 1.25)%, and the use of statistical analysis (ANOVA) to contrast the differences and Dnken test to the variation in any disinfectant or the most efficient concentrations of other disinfectants were observed that concentrations of 5% was the most efficient of concentrations than (2.5%) and (1.25%). As the disinfectant Dettol was significantly the most efficient from Bleach and Hibitane.

Étude des caractéristiques physicochimiques et de l’activité antifongique des huiles essentielles d’Erigeron floribundus (Kunth.) Sch. Bip

2021 ◽  
Author(s):  
E.V. Tia ◽  
A.A. Adima ◽  
C. Menut
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Cote D'ivoire ◽  
Trichophyton Mentagrophytes ◽  
Huiles Essentielles ◽  
Huile Essentielle ◽  
Plantes Médicinales ◽  
Médecine Traditionnelle ◽  
Milieu Rural ◽  
Erigeron Floribundus

L’usage des plantes médicinales connaît un regain d’intérêt. Cela est lié à la toxicité des produits chimiques, au coût élevé des médicaments chimiques, à l’éloignement et/ou l’insuffisance des centres de santé surtout en milieu rural. L’objectif général de cette étude était d’évaluer les potentialités thérapeutiques de l’huile essentielle des feuilles de l’espèce Erigeron floribundus utilisées en médecine traditionnelle en Côte-d’Ivoire. Les rendements en huile essentielle des feuilles d’Erigeron floribundus varient de 0,16 % pour les feuilles fraîches et de 0,31 % pour les feuilles séchées. Les indices physiques et chimiques de ces huiles essentielles sont en adéquation avec les critères de qualité des huiles essentielles selon la norme Afnor. L’effet antifongique des deux types d’huiles essentielles a été très remarquable sur les souches fongiques testées, notamment Trichophyton mentagrophytes et Aspergillus fumigatus, avec un effet moindre sur Candida albicans. Cette étude valide ainsi scientifiquement les usages traditionnels des extraits de la plante Erigeron floribundus en médecine traditionnelle.

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