scholarly journals Antifungal Drugs Influence Neutrophil Effector Functions

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Frederic Ries ◽  
Astrid Alflen ◽  
Pamela Aranda Lopez ◽  
Hendrik Beckert ◽  
Matthias Theobald ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Polymorphonuclear Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Activation Markers ◽  
Effector Functions ◽  
Enhanced Expression ◽  
Almost All

ABSTRACTThere is a growing body of evidence for immunomodulatory side effects of antifungal agents on different immune cells, e.g., T cells. Therefore, the aim of our study was to clarify these interactions with regard to the effector functions of polymorphonuclear neutrophils (PMN). Human PMN were preincubated with fluconazole (FLC), voriconazole (VRC), posaconazole (POS), isavuconazole (ISA), caspofungin (CAS), micafungin (MFG), conventional amphotericin B (AMB), and liposomal amphotericin B (LAMB). PMN then were analyzed by flow cytometry for activation, degranulation, and phagocytosis and by dichlorofluorescein assay to detect reactive oxygen species (ROS). Additionally, interleukin-8 (IL-8) release was measured by enzyme-linked immunosorbent assay. POS led to enhanced activation, degranulation, and generation of ROS, whereas IL-8 release was reduced. In contrast, ISA-pretreated PMN showed decreased activation signaling, impaired degranulation, and lower generation of ROS. MFG caused enhanced expression of activation markers but impaired degranulation, phagocytosis, generation of ROS, and IL-8 release. CAS showed increased phagocytosis, whereas degranulation and generation of ROS were reduced. AMB led to activation of almost all effector functions besides impaired phagocytosis, whereas LAMB did not alter any effector functions. Independent from class, antifungal agents show variable influence on neutrophil effector functionsin vitro. Whether this is clinically relevant needs to be clarified.

scholarly journals In Vitro and In Vivo Experimental Activities of Antifungal Agents against Fusarium solani

1999 ◽  
Vol 43 (5) ◽  
pp. 1256-1257 ◽  
Author(s):  
J. Guarro ◽  
I. Pujol ◽  
E. Mayayo
Keyword(s):  
Drug Therapy ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Disseminated Infection

ABSTRACT In the treatment of disseminated Fusarium infections, amphotericin B either alone or in combination with flucytosine and rifampin is the drug therapy most frequently used. The efficacy of these antifungal drugs was evaluated in a murine disseminated-infection model, with five strains of Fusarium solani. All the treatments were clearly ineffective.

scholarly journals Susceptibility of Cryptococcus neoformans Biofilms to Antifungal Agents In Vitro

2006 ◽  
Vol 50 (3) ◽  
pp. 1021-1033 ◽  
Author(s):  
Luis R. Martinez ◽  
Arturo Casadevall
Keyword(s):  
Confocal Microscopy ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Capsular Polysaccharide ◽  
Antifungal Drugs ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sequence Of Events ◽  
Biofilm Development

ABSTRACT Microbial biofilms contribute to virulence and resistance to antibiotics by shielding microbial cells from host defenses and antimicrobial drugs, respectively. Cryptococcus neoformans was demonstrated to form biofilms in polystyrene microtiter plates. The numbers of CFU of disaggregated biofilms, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide reduction, and light and confocal microscopy were used to measure the fungal mass, the metabolic activity, and the appearance of C. neoformans biofilms, respectively. Biofilm development by C. neoformans followed a standard sequence of events: fungal surface attachment, microcolony formation, and matrix production. The susceptibilities of C. neoformans cells of the biofilm and planktonic phenotypes to four antifungal agents were examined. The exposure of C. neoformans cells or preformed cryptococcal biofilms to fluconazole or voriconazole did not result in yeast growth inhibition and did not affect the metabolic activities of the biofilms, respectively. In contrast, both C. neoformans cells and preformed biofilms were susceptible to amphotericin B and caspofungin. However, C. neoformans biofilms were significantly more resistant to amphotericin B and caspofungin than planktonic cells, and their susceptibilities to these drugs were further reduced if cryptococcal cells contained melanin. A spot enzyme-linked immunosorbent assay and light and confocal microscopy were used to investigate how antifungal drugs affected C. neoformans biofilm formation. The mechanism by which amphotericin B and caspofungin interfered with C. neoformans biofilm formation involved capsular polysaccharide release and adherence. Our results suggest that biofilm formation may diminish the efficacies of some antifungal drugs during cryptococcal infection.

scholarly journals Effect of antifungal agents, lysozyme and human antimicrobial peptide LL-37 on clinical Candida isolates with high biofilm production

2020 ◽  
Author(s):  
Yi-Chun Chen ◽  
Fang-Ju Chen ◽  
Chen-Hsiang Lee
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Synergistic Effects ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Xtt Assay ◽  
Biofilm Production ◽  
Visual Reading

Introduction. Candida species can form biofilms on tissues and medical devices, making them less susceptible to antifungal agents. Hypothesis/Gap Statement. Antifungal combination may be an effective strategy to fight against Candida biofilm. Aim. In this study, we investigated the in vitro activity of fluconazole, caspofungin and amphotericin B, alone and in combination, against 17 clinical Candida tropicalis and 6 Candida parapsilosis isolates with high biofilm formation. We also tested LL-37 and lysozyme for anti-biofilm activity against a selected C. tropicalis isolate. Methodology. Candida biofilms were prepared using the 96-well plate-based method. The minimum biofilm eradication concentrations were determined for single and combined antifungal drugs. The activity of LL-37 and lysozyme was determined by visual reading for planktonic cells and using the XTT assay for biofilms. Results. Under biofilm conditions, fluconazole plus caspofungin showed synergistic effects against 60.9% (14 of 23) of the tested isolates, including 70.6% of C. tropicalis [fractional inhibitory concentration index (FICI), 0.26–1.03] and 33.3% of C. parapsilosis (FICI, 0.04–2.03) isolates. Using this combination, no antagonism was observed. Amphotericin B plus caspofungin showed no effects against 78.3% (18 of 23) of the tested isolates. Amphotericin B plus fluconazole showed no effects against 65.2% (15 of 23) of the tested isolates and may have led to antagonism against 2 C. tropicalis and 2 C. parapsilosis isolates. LL-37 and lysozyme had no effect on biofilms of the selected C. tropicalis isolate. Conclusions. We found that fluconazole plus caspofungin led to a synergistic effect against C. tropicalis and C. parapsilosis biofilms. The efficacy of the antifungal combination therapies of the proposed schemes against biofilm-associated Candida infections requires careful and constant evaluation.

scholarly journals Antifungal Susceptibility of Non-albicans Candida Species in A Tertiary Care Hospital, Bulgaria

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Hristina Yotova Hitkova ◽  
Diana Simeonova Georgieva ◽  
Preslava Mihailova Hristova ◽  
Teodora Vasileva Marinova-Bulgaranova ◽  
Biser Kirilov Borisov ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Tertiary Care ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Care Hospital ◽  
And Control

Background: Emerging non-albicans Candida (NAC) species are a major threat because of their intrinsic or acquired resistance to routinely applied antifungal agents. Objectives: The purpose of our study was to reveal in vitro activity of nine antifungal agents against NAC isolates. Methods: A total of 67 NAC (27 Candida glabrata, 10 C. tropicalis, 6 C. krusei, 6 C. parapsilosis, 4 C. lusitaniae, 4 C. lipolytica, etc.) were identified and tested. The antifungal susceptibility was estimated on the basis of minimum inhibitory concentrations (MIC). Results: Overall, 13 species were determined, of which C. glabrata was the most common (40.3%), followed by C. tropicalis (14.9%), C. krusei, and C. parapsilosis (8.9 % each). Forty-nine NAC isolates (73.13%) demonstrated decreased susceptibility to one or more antifungals, and 18 of them were resistant to all azoles. Out of 27 C. glabrata, 12 (44.4%) were resistant to fluconazole with MICs: 32 - >128 µg/mL and 15 (55.6%) were intermediate with MICs: 8 - 16 µg/mL Non-albicans Candida revealed a good susceptibility to echinocandins. Amphotericin B resistance was found in 5.97% of the isolates. Of particular interest was the detection of 6 (8.95%) multidrug-resistant NAC, which expressed resistance to azoles and echinocandins and/or amphotericin B. Conclusions: About one-fourth of the studied NAC were resistant to all azoles. These findings as well as the detection of several multidrug-resistant isolates determine the necessity of susceptibility testing of clinically important yeast isolates and control of the antifungal drugs in our hospital.

In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates ofCandida spp.

1998 ◽  
Vol 42 (1) ◽  
pp. 161-163 ◽  
Author(s):  
F. Marco ◽  
M. A. Pfaller ◽  
S. Messer ◽  
R. N. Jones
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Clinical Laboratory ◽  
Candida Krusei ◽  
Antifungal Drugs ◽  
National Committee ◽  
In Vitro Activity ◽  
Medical Centers

ABSTRACT Voriconazole (formerly UK-109,496) is a new monotriazole antifungal agent which has potent activity against Candida,Cryptococcus, and Aspergillus species. We investigated the in vitro activity of voriconazole compared to those of fluconazole, itraconazole, amphotericin B, and flucytosine (5FC) against 394 bloodstream isolates of Candida (five species) obtained from more than 30 different medical centers. MICs of all antifungal drugs were determined by the method recommended by the National Committee for Clinical Laboratory Standards using RPMI 1640 test medium. Overall, voriconazole was quite active against all the yeast isolates (MIC at which 90% of the isolates are inhibited [MIC90], ≤0.5 μg/ml). Candida albicans was the most susceptible species (MIC90, 0.06 μg/ml) andCandida glabrata and Candida krusei were the least (MIC90, 1 μg/ml). Voriconazole was more active than amphotericin B and 5FC against all species except C. glabrata and was also more active than itraconazole and fluconazole. For isolates of Candida spp. with decreased susceptibility to fluconazole and itraconazole MICs of voriconazole were also higher. Based on these results, voriconazole has promising antifungal activity and further in vitro and in vivo investigations are warranted.

scholarly journals In Vitro Interactions of Approved and Novel Drugs against Paecilomyces spp

2004 ◽  
Vol 48 (7) ◽  
pp. 2727-2729 ◽  
Author(s):  
Montserrat Ortoneda ◽  
Javier Capilla ◽  
F. Javier Pastor ◽  
Isabel Pujol ◽  
Clara Yustes ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Paecilomyces Variotii ◽  
Novel Drugs ◽  
In Vitro Interactions

ABSTRACT We have evaluated the in vitro activity of 15 combinations of antifungal drugs (amphotericin B, itraconazole, voriconazole, albaconazole, ravuconazole, terbinafine, and micafungin) against four isolates of Paecilomyces variotii and three of P. lilacinus. The interaction of terbinafine with the four azoles was synergistic for 53% of the combinations, while the interactions of both amphotericin B and micafungin with the rest of antifungal agents were mainly indifferent.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

scholarly journals Spectrum and theIn VitroAntifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Birhan Moges ◽  
Adane Bitew ◽  
Aster Shewaamare
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Assay Method ◽  
Cryptococcus Laurentii ◽  
Susceptibility Pattern ◽  
Test Procedures ◽  
Disk Diffusion Assay ◽  
Diffusion Assay

Background.In Ethiopia, little is known regarding the distribution and thein vitroantifungal susceptibility profile of yeasts.Objective.This study was undertaken to determine the spectrum and thein vitroantifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC.Method.Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method.Result.One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART.C. albicanswas the most frequently isolated species followed byC. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorulaspecies. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively.Conclusion.Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs.

scholarly journals In VitroActivities of Nine Antifungal Drugs against 81 Phialophora and Cyphellophora Isolates

2012 ◽  
Vol 56 (11) ◽  
pp. 6044-6047 ◽  
Author(s):  
Peiying Feng ◽  
M. Javad Najafzadeh ◽  
Jiufeng Sun ◽  
Sarah Ahmed ◽  
Liyan Xi ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Drugs ◽  
Content Type

ABSTRACTCyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.

scholarly journals Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Content Type ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Pass Through

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.

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