EPIDEMIOLOGY AND TREATMENT OF FUNGAL INFECTIONS IN ONCO-PEDIATRIC PATIENTS AT A REFERRAL HOSPITAL

Aim: to identify the epidemiology of fungal infections in the pediatric service of a reference hospital for the treatment of cancer for 2016 to 2019, through the dispensing of antifungal drugs by the hospital pharmacy. Methods: Retrospective cohort analysis of 1.211 antifungal requests. Results and Discussion: 1.211 treatments with antifungal agents were performed in the period, with 71.9% of cases treated with empirical therapy, 64.1% of cases of mucocutaneous candidiasis and with the use of nystatin in 48.6% of cases. There were 114 episodes of IFIs, in which probable fungal pneumonia represented 40.4% of the therapeuticindications, based on suggestive tomographic images and clinical and epidemiological criteria in 40.3% of cases. Conclusions: There was an agreement between the epidemiology of fungal infections and the worldwide epidemiology, but there was disagreement between the therapies applied in the study hospital and the recent guidelines.

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Potential of Nanoparticles in Combating Candida Infections

Letters in Drug Design & Discovery ◽

10.2174/1570180815666181015145224 ◽

2019 ◽

Vol 16 (5) ◽

pp. 478-491 ◽

Cited By ~ 5

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.

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Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00156-18 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 32

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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Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa157 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lisa Kirchhoff ◽

Silke Dittmer ◽

Ann-Kathrin Weisner ◽

Jan Buer ◽

Peter-Michael Rath ◽

...

Keyword(s):

Amphotericin B ◽

Biofilm Formation ◽

Laser Scanning ◽

Antifungal Agents ◽

Fungal Infections ◽

Pathogenic Fungus ◽

Antifungal Drugs ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

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Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

Mediators of Inflammation ◽

10.1155/2017/9870679 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 22

Author(s):

Juliana Alves Parente-Rocha ◽

Alexandre Melo Bailão ◽

André Correa Amaral ◽

Carlos Pelleschi Taborda ◽

Juliano Domiraci Paccez ◽

...

Keyword(s):

Drug Targets ◽

Antifungal Agents ◽

Fungal Infections ◽

Public Health Problem ◽

Antifungal Drugs ◽

Fungal Resistance ◽

Immunocompromised Patients ◽

Dimorphic Fungi ◽

Novel Drug ◽

Novel Drug Targets

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

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CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

BioMed Research International ◽

10.1155/2013/204237 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 91

Author(s):

Claudia Spampinato ◽

Darío Leonardi

Keyword(s):

Antifungal Agents ◽

Fungal Infections ◽

Current Knowledge ◽

Resistance Mechanisms ◽

Antifungal Drugs ◽

Diagnostic Methods ◽

Opportunistic Pathogens ◽

Yeast Infection ◽

Life Threatening ◽

Therapeutic Alternatives

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.

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Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00924-20 ◽

2020 ◽

Vol 64 (9) ◽

Cited By ~ 2

Author(s):

Gina Wall ◽

Jose L. Lopez-Ribot

Keyword(s):

Antifungal Activity ◽

Antifungal Agents ◽

Fungal Infections ◽

Alternative Pathway ◽

Drug Repurposing ◽

Pathogenic Fungi ◽

Multidrug Resistant ◽

Modern Medicine ◽

Antifungal Drugs ◽

Promising Alternative

ABSTRACT Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents. Unfortunately, the development of a novel antifungal is a rather long and expensive proposition, and no new classes of antifungal agents have reached the market in the last 2 decades. Drug repurposing, or finding new indications for old drugs, represents a promising alternative pathway to drug development that is particularly appealing within the academic environment. In the last few years, there has been a growing interest in repurposing approaches in the antifungal arena, with multiple groups of investigators having performed screenings of different repurposing libraries against different pathogenic fungi in search for drugs with previously unrecognized antifungal effects. Overall, these repurposing efforts may lead to the fast deployment of drugs with novel antifungal activity, which can rapidly bring benefits to patients, while at the same time reducing health care costs.

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‘Acridines’ as New Horizons in Antifungal Treatment

Molecules ◽

10.3390/molecules25071480 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1480 ◽

Cited By ~ 2

Author(s):

Iwona Gabriel

Keyword(s):

Antifungal Agents ◽

Fungal Infections ◽

Chemotherapeutic Agents ◽

Antifungal Drugs ◽

New Horizons ◽

Acridine Derivatives ◽

Hybrid Molecules ◽

Invasive Mycosis ◽

Opportunistic Pathogenic ◽

Clinical Problems

Frequent fungal infections in immunocompromised patients and mortality due to invasive mycosis are important clinical problems. Opportunistic pathogenic Candida species remain one of the leading causes of systemic mycosis worldwide. The repertoire of antifungal chemotherapeutic agents is very limited. Although new antifungal drugs such as lanosterol 14α-demethylase and β-glucan synthase inhibitors have been introduced into clinical practice, the development of multidrug resistance has become increasingly significant. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets to the conventional ones currently used. Among them, many compounds containing an acridine scaffold have been synthesized and tested. In this review, the applicability of acridines and their functional analogues acridones as antifungal agents is described. Acridine derivatives usage in photoantifungal chemotherapy, interactions with fungal transporters resulting in modulation of efflux/influx pumps and the effect of acridine derivatives on fungal topoisomerases are discussed. This article explores new perspectives on the mechanisms of antifungal acridine-peptide conjugates and acridine-based hybrid molecules to effectively combat fungal infections.

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Review on Antifungal Agents

Research Journal of Pharmacology and Pharmacodynamics ◽

10.52711/2321-5836.2021.00028 ◽

2021 ◽

pp. 147-154

Author(s):

Sangita P. Shirsat ◽

Kaveri P. Tambe ◽

Ganesh G. Dhakad ◽

Paresh A. Patil ◽

Ritik. S. Jain

Keyword(s):

Adverse Effects ◽

First Generation ◽

Antifungal Agents ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Antifungal Drugs ◽

Liver Transaminase ◽

Spectrum Activity ◽

Anti Fungal ◽

Visual Disturbances

There are so many type of daisies are founded because of ‘Fungal’ such daisies given in follow. also the treatment on this particular daisies with the help of ‘Anti-fungal’ drug or anti- fungal agent and anti-fungal medication as follows The four main classes of antifungal drugs are the polyenes, Azoles, allylamines and echinocandins. Clinically useful “older” agents include topical azole Formulations (for superficial yeast and dermatophyte Infections), first-generation triazoles (fluconazole and Itraconazole, for a range of superficial and invasive fungal Infections), amphotericin B formulations (for a broad range of Invasive fungal infections) and terbinafine (for dermatophyte Infections). Clinically important “newer” agents include members of the Echinocandin class (eg, caspofungin) and second-generation Triazoles (eg, voriconazole and posaconazole). Voriconazole and posaconazole have broad-spectrum activity Against yeasts and moulds, including Aspergillus species. Posaconazole is the only azole drug with activity against Zygomycete fungi. Caspofungin and the other echinocandins are effective in Treating Candida and Aspergillus infections. The azoles are relatively safe, but clinicians should be aware of drug–drug interactions and adverse effects, including Visual disturbances (with voriconazole), elevations in liver Transaminase levels, and skin rashes. Caspofungin has Minimal adverse effects. Combination antifungal therapy may be appropriate in Selected patients with invasive fungal infections, but is Empiric and driven by individual physician practice. Clinical needs for novel antifungal agents have altered

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Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment

Future Medicinal Chemistry ◽

10.4155/fmc-2021-0162 ◽

2021 ◽

Author(s):

Peng-Li Zhang ◽

Gopala Lavanya ◽

Yang Yu ◽

Bo Fang ◽

Cheng-He Zhou

Keyword(s):

Antioxidant Defense ◽

Antifungal Agents ◽

Fungal Infections ◽

Antioxidant Defense System ◽

Antifungal Drugs ◽

Defense System ◽

High Incidence ◽

Dynamic Treatment ◽

Low Toxicity ◽

Treatment Window

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti- Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

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Pre-Existing Liver Disease and Toxicity of Antifungals

Journal of Fungi ◽

10.3390/jof4040133 ◽

2018 ◽

Vol 4 (4) ◽

pp. 133 ◽

Cited By ~ 7

Author(s):

Nikolaos Spernovasilis ◽

Diamantis Kofteridis

Keyword(s):

Decision Making ◽

Liver Disease ◽

Antifungal Agents ◽

Dosage Adjustment ◽

Fungal Infections ◽

Drug Efficacy ◽

Antifungal Drugs ◽

Current Evidence ◽

Comprehensive Review

Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo.

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