Antifungal
Antifungal refers to substances or medications that are used to treat or prevent fungal infections. These can include topical creams, oral medications, or intravenous treatments. Antifungals work by targeting the fungal cells and inhibiting their growth or killing them, helping to alleviate symptoms and eradicate the infection.
7 Key excerpts on "Antifungal"
eBook - ePubFungi
Applications and Management Strategies
- Sunil K. Deshmukh, J. K. Misra, Jalpa P. Tewari, Tamas Papp, Sunil K. Deshmukh, J. K. Misra, Jalpa P. Tewari, Tamas Papp(Authors)
- 2018(Publication Date)
- CRC Press(Publisher)
...Compounds isolated from natural sources (variety of chemotherapeutic agents) provide a wealth of bioactive molecules that in some cases have been directly used as drugs or as lead for the development of potent inhibitors useful for the characterization of enzymes of interest, and to design future therapeutic drugs (Singh and Pelaez, 2008; Fischbach and Walsh, 2009). These agents have greatly contributed to the improvement of human health over the past century. Despite the state-of-the-art Antifungal therapy, the mortality rates for invasive infections from the three most common species of human fungal pathogens (Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans) are between 40-90% (Lai et al., 2008; Park et al., 2009). Unfortunately, researches on Antifungal agents is limited as compared to the number of agents available for bacterial infections. In fact, it took 20 years for the newest class of Antifungal drugs, the echinocandins, to progress from bench-to-bedside. Until the 1970s, fungal infections were considered largely treatable and the demand for new medicines to treat them was very limited. Before this period, Antifungal chemotherapy included only two kinds of compounds: potassium iodide, effective in the treatment of sporotrichosis; and the polyenes: amphotericin B, nystatin and pimaricin, which were introduced in the 1950s; amphotericin B for the treatment of severe systemic mycoses and nystatin and pimaricin for cutaneous, vaginal and intestinal candidiasis. Except for the development of flucytosine (first synthesized in 1957 but its Antifungal properties were discovered in 1964), there was little progress until the development of the azole drugs in the early 1970s. Therefore, only a limited number of Antifungal agents (polyenes and azoles plus the recently introduced echinocandins) are currently available for the treatment of life-threatening fungal infections...
eBook - ePub- J. W. Deacon(Author)
- 2013(Publication Date)
- Wiley-Blackwell(Publisher)
...Similarly, the naturally occurring Antifungal antibiotic griseofulvin was first discovered as a “curling factor” that caused the germ-tubes of a plant-pathogenic fungus, Botrytis allii, to grow in a distorted spiral fashion, but it was developed commercially as an orally administered antibiotic to control infections caused by the dematophytic fungi. It acts by disrupting fungal microtubules, and this explains its morphogenetic effect because microtubules are involved in the delivery of cellular components to the growing hyphal tip (Chapter 4). Principal cellular targets of Antifungal agents The main cellular targets currently used to control plant or human diseases are shown in Fig. 17.2. At first sight it might seem that there are a large number of cellular targets that could be exploited for disease control. But in practice the range is limited. Many of the compounds shown in Fig. 17.2 have a very restricted usage (shown as “R”) and are used mainly in Japanese agriculture. If we exclude these compounds then we are left with just five main types of Antifungal target : 1 the cell membrane, because fungi are unique in having ergosterol as their characteristic membrane sterol; 2 the microtubules and microtubule-associated proteins, which are disrupted by the antibiotic griseofulvin, and by benzimidazole fungicides (which have now been withdrawn); 3 mitochondrial respiration, which is targeted by some plant fungicides; 4 fungal cell wall components, especially β1-3 glucans, for which a new group of drugs, the echinocandins, has recently come into use (2002); 5 various aspects of general metabolism. Fig. 17.2 The main cellular targets for chemical control of fungi that cause plant and human diseases...
eBook - ePub- Mahmoud Ghannoum, Matthew Parsek, Marvin Whiteley, Pranab K. Mukherjee, Mahmoud Ghannoum, Matthew Parsek, Marvin Whiteley, Pranab K. Mukherjee(Authors)
- 2015(Publication Date)
- ASM Press(Publisher)
...19 From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms CHRISTOPHER G. PIERCE, 1, 3 ANAND SRINIVASAN, 2, 3 ANAND K. RAMASUBRAMANIAN, 2, 3 and JOSÉ L. LÓPEZ-RIBOT 1, 3 INTRODUCTION Advances in modern medicine are prolonging the lives of severely ill individuals; however, at the same time they are creating an expanding population of compromised patients at increased risk of suffering from invasive fungal infections (1). These include surgical, transplant, cancer, intensive care unit, and HIV-infected patients, as well as neonates. The use of broad-spectrum antibiotics, parenteral nutrition, medical implant devices, and immune suppression, as well as disruption of mucosal barriers due to surgery, chemotherapy, and radiotherapy represent the most important predisposing factors for these infections. Unfortunately, the mortality rates associated with these fungal infections remain unacceptably high, which clearly points to the many limitations of current Antifungal therapy, including the limited armamentarium of Antifungal agents, their inherent toxicity, and the emergence of resistance (2 – 4). Fungi are eukaryotic organisms, and there is a paucity of selective targets which can be exploited for Antifungal drug development, while at the same time this is also the main reason for the elevated toxicity of some of the current agents (2, 3, 5). Only three classes of Antifungal agents—azoles, polyenes, and echinocandins—constitute the mainstay of Antifungal therapy for patients with life-threatening invasive fungal infections. Moreover, the Antifungal drug pipeline is mostly dry and, with the exception of isavuconazole, no new agents are expected to reach the market any time soon (2). The formation of biofilms by many pathogenic fungi further complicates treatment (4). Biofilms are attached and structured microbial communities surrounded by a protective exopolymeric matrix (6 – 8)...
eBook - ePub- Atta-ur-Rahman, Shazia Anjum, Hesham R. El-Seedi(Authors)
- 2018(Publication Date)
- Bentham Science Publishers(Publisher)
...They inhibit the synthesis of D-glucan against Aspergillus, dimorphic molds, and Pneumocystis carinii. Their mechanism of fungal inhibition was found to be the alteration in fungal cell membrane composition and increase in the activity of efflux pump. The increase in the Antifungal agents has created an impact and certainly increased the frequency of resistance to a number of fungal species. Increase in resistance mostly affects the morbidity rate, mortality rate and patient health care in population. There is a large arsenal of Antifungal drugs; however, their cellular targets are limited because of the similarity that exists between fungi and host cells. Despite the great success of Antifungal agents in the treatment of fungal infection, there are some cases of developing resistance to Antifungal agents by various fungal species. Increase in resistance mostly affects the morbidity rate, mortality rate and patient health care in population. Global prevalence and emerging problem with Antifungal agents are their resistance, and the fact that around 3 to 6% of fungal species are naturally resistant to Antifungal medication [ 44 ]. Nowadays, also a treatment for fungal infections is complex, as eukaryotic fungi have similar structures and metabolism with the host cell. This feature is often responsible for the toxicity, thus despite extensive research carried out for the development of new therapeutic strategies, only a limited number of drugs are available for the treatment of invasive fungal infections. Thus, there is an extensive need for the development of new Antifungal agents in clinical therapy. At present, the major problem evolved in the treatment of these infections and related diseases is the increasing appearance of multiresistant strains (MDR)...
eBook - ePubFungi
Biology and Applications
- Kevin Kavanagh, Kevin Kavanagh(Authors)
- 2011(Publication Date)
- Wiley(Publisher)
...They are either topical (treat local infections) or systemic (treat systemic and disseminated infections) and they can be naturally derived (antibiotic) or chemically synthesized (synthetic). Table 11.1 Commonly used Antifungal drugs. Class and agents General mechanism of action Susceptible fungi I. Active against plasma membrane integrity or synthesis Polyenes (AMB and nystatin) Autooxidation of ergosterol and formation of free radicals which compromise plasma membrane integrity and increase permeability Different species of Candida, Aspergillus, Histoplasma, Coccidioides, Cryptococcus and Saccharomyces Azoles (imidazoles and triazoles) Inhibit ergosterol synthesis by blocking the activity of the P450-dependent enzyme 14 α-demethylase Different species of Candida, Aspergillus and Cryptococcus Echinocandins (cilofungin) Allylamines (terbinafine and naftifine), Thiocarbamates (tolnaftate) Inhibit the activity of squalene epoxidase, which is responsible for the cyclization of squalene to lanosterol Different species of Aspegillus, Fusarium, Penicillium, Trichoderma, Acremonuim and Arthrographis Octenidine and Pirtenidine Affect ergosterol biosynthesis by inhibition of 14α –. demethylase C. albicans, S. cerevisiae Sphingofungin Interrupts sphingolipid synthesis by inhibiting serine palmitoyltrasferase activity Different fungal species Floimycin (concanamycin A) Hydroxypyridones Inhibitor of V-type Proton-ATPase Different fungal species Inhibits ATP-synthesis and cellular uptake of essential components II. Active against cell-wall components Echinocandins (caspofungin, micafungin anidulafungin) Inhibit cell-wall glucan synthesis by blocking (1,3)-β-D glucan synthase activity Candida spp. Nikkomycin, Aureobasidin, Polyoxins Inhibit chitin synthesis and assembly Candida and Cryptococcus spp. Pradimicin A Calcium-dependent complexing with saccharides of manno protein and disruption of membrane causing leakage of intracellular potassium Candida and Aspergillus spp...
eBook - ePub- Mahmoud A. Ghannoum, John R. Perfect, Mahmoud A. Ghannoum, John R. Perfect(Authors)
- 2019(Publication Date)
- CRC Press(Publisher)
...Coincidently, novel therapies that target host defenses, fungal biofilm physiology, and emerging resistances must be developed in order to keep pace with changes in the etiology and the resistance patterns of fungal pathogens. EARLY TREATMENTS Antifungal therapies evolved slowly during the early years of the past century. For example, from the beginning of the twentieth century until after World War II, potassium iodide was the standard treatment for cutaneous fungal infections, including actinomycosis, blastomycosis, sporotrichosis, and tinea [ 5 ]. First derived from sea algae, potassium iodide was considered to exert a direct Antifungal effect, although the complete mechanism of action remains unclear [ 6, 7, 8 ]. Contemporarily, radiation was used to treat severe tinea capitis infections, often with significant complications, including skin cancer and brain tumors [ 9 ]. In the 1940s, Mayer et al. [ 10 ] demonstrated that sulfonamide drugs, such as sulfadiazine, exhibited both fungistatic and fungicidal activities against Histoplasma capsulatum [ 11 ]. This discovery led to the formation and the use of sulfonamide derivatives for the treatment of blastomycosis, nocardiosis, and cryptococcosis [ 12, 13, 14 ]. Griseofulvin, a compound derived from Penicillium griseofulvum, has been widely used to treat superficial fungal infections since its isolation in 1939 [ 15 ]. In 1958, Gentles [ 16 ] reported the successful treatment of ringworm in guinea pigs using oral griseofulvin. These successful attempts to develop novel and effective Antifungal drugs encouraged the further study and discovery of new agents. AntifungalS FOR THE TREATMENT OF INVASIVE INFECTIONS Polyenes In 1946, polyene Antifungals (Figure 1.1), which are effective against organisms with sterol-containing cell membranes (e.g., yeast, algae, and protozoa), were developed from the fermentation of Streptomyces [ 17, 18 ]...
- B. D. Kaushik, Deepak Kumar, Md. Shamim, B. D. Kaushik, Deepak Kumar, Md. Shamim(Authors)
- 2019(Publication Date)
- Apple Academic Press(Publisher)
...There are also few necessary elements for the development of special formulations to ensure the effectiveness of agents applied in the field. An extended dew period is needed by few pathogens for infection on the aerial surfaces of target weeds (Auld et al., 2003). The bioherbicide application process should be judged for enhancing efficacy of the BCA. These include attention to spray droplet size, droplet retention and distribution, spray application volume, and the equipment used (Charudattan, 2001). Other factors, such as the spectrum of the bioherbicide, whether broad or targeted to specific species, the type of formulation, and if it involves amino acid-excreting strains, can significantly affect efficacy. Broad-spectrum and Abbas, 1994). 3.8 Conclusion The relevance of fungal biopesticides in biological control is increasing largely because of superior environmental awareness, food safety concerns, and the breakdown of conventional chemicals due to an increasing number of insecticide-resistant species. In formative, whether the use of fungal biopesticides have been thriving in pest and disease management, it is necessary to regard as each case individually, and direct comparisons with chemical insecticides are usually unsuitable. Fungal biopesticides being component of an integrated advancement that can offer significant and selective insect and disease control. In the near future, we suppose to see synergistic combinations of microbial control agents with other technologies (in combination with semiochemicals, soft chemical pesticides, fungicides, other natural enemies, resistant plants, chemigation, remote sensing, etc.) that will augment the effectiveness and sustainability of integrated control strategies of plant disease. Keywords fungal biopesticides pest control ecofriendly approach insect pest agriculture References Abdel-Fattah, M. G.; Shabana, M. Y.; Ismail, E. A.; Rashad, M...
