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Seminars in Respiratory and Critical... Oct 2015Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black... (Review)
Review
Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black molds. It is also effective for infections caused by Candida species, including those that are fluconazole resistant, and for infections caused by the endemic mycoses, including those that occur in the central nervous system. It has the advantage of being available in both an intravenous and an oral formulation that is well absorbed. Drawbacks to the use of voriconazole are that it has unpredictable, nonlinear pharmacokinetics with extensive interpatient and intrapatient variation in serum levels. Some of the adverse effects seen with voriconazole are related to high serum concentrations, and, as a result, therapeutic drug monitoring is essential when using this agent. Drug-drug interactions are common, and possible interactions must be sought before voriconazole is prescribed. With prolonged use, newly described adverse effects, including periostitis, alopecia, and development of skin cancers, have been noted.
Topics: Antifungal Agents; Drug Interactions; Drug Monitoring; Humans; Mycoses; Voriconazole
PubMed: 26398543
DOI: 10.1055/s-0035-1562903 -
Drugs Jun 2019Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of... (Review)
Review
Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of time, particularly in patients with hematologic malignancies, or in those who have received a solid organ or hematopoietic stem cell transplant. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, decreased libido, oligospermia, azoospermia, impotence, hypokalemia, hyponatremia, and (rarely) adrenal insufficiency. Voriconazole and posaconazole have been associated with peripheral neuropathies, and itraconazole and voriconazole with pancreatitis. In addition, voriconazole has been associated with periostitis, phototoxic reactions, and squamous cell carcinoma. Since many at-risk patients are commonly receiving multiple medications, it can be difficult for care providers to identify antifungal agent causality or contribution to patient symptoms. Knowledge and recognition of adverse events caused by azoles, leading to dose reduction or discontinuation, can generally reverse these adverse events.
Topics: Antifungal Agents; Azoles; Chemical and Drug Induced Liver Injury; Databases, Factual; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Time Factors
PubMed: 31093949
DOI: 10.1007/s40265-019-01127-8 -
Expert Opinion on Drug Metabolism &... Nov 2019: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a... (Review)
Review
: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy.: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies.: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.
Topics: Adult; Antifungal Agents; Child; Drug Development; Drug Monitoring; Humans; Invasive Fungal Infections
PubMed: 31550939
DOI: 10.1080/17425255.2019.1671971 -
Science (New York, N.Y.) Aug 1961From the soil of the San Joaquin Valley a fungus has been isolated, an extract of which inhibits the growth of Coccidioides immitis on Sabouraud's medium. An acute...
From the soil of the San Joaquin Valley a fungus has been isolated, an extract of which inhibits the growth of Coccidioides immitis on Sabouraud's medium. An acute toxicity study in mice indicates a certain tolerance of the extract. Tentative identification indicates that the fungus is a penicillium.
Topics: Animals; Antifungal Agents; Coccidioides; Fungi; Fungicides, Industrial; Mice; Penicillium; Soil; Soil Microbiology
PubMed: 13725895
DOI: 10.1126/science.134.3477.472 -
Clinical Therapeutics Mar 2002The mainstays of treatment for nosocomial fungal infections have been amphotericin B and azole derivatives. Caspofungin acetate is a new echinocandin antifungal agent... (Review)
Review
BACKGROUND
The mainstays of treatment for nosocomial fungal infections have been amphotericin B and azole derivatives. Caspofungin acetate is a new echinocandin antifungal agent with a mechanism of action that targets a structural component of the fungal cell wall.
OBJECTIVE
This article describes the pharmacologic properties and potential clinical usefulness of caspofungin.
METHODS
Relevant information was identified through searches of MEDLINE (1966-September 2001). Iowa Drug Information Service (1966-September 2001), and International Pharmaceutical Abstracts (1970-September 2001), as well as meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996-2001), using the terms caspofungin, MK-0991, pneumocandin, echinocandin, candin, and beta-(1,3)-glucan inhibitor.
RESULTS
In vitro, caspofungin exhibits antifungal activity against an array of clinically important yeasts and molds, including Candida and Aspergillus spp. The proposed susceptibility breakpoint for caspofungin against Candida spp, the most common cause of nosocomial fungal infections, is a minimum inhibitory concentration of < or =1 microg/mL. In humans, caspofungin has a volume of distribution of 9.67 L, is extensively bound to albumin (97%), has a plasma elimination half-life of 9 to 11 hours, and is metabolized to inactive metabolites in the liver. Dose adjustment based on age, sex, race, or renal function does not appear to be necessary, although patients with moderate hepatic insufficiency (Child-Pugh score 7-9) should receive a lower maintenance dose. The results of clinical trials, although somewhat preliminary, suggest that caspofungin is effective in the treatment of esophageal and oropharyngeal candidiasis and invasive aspergillosis. When combined with other antifungal agents, caspofungin produces a synergistic or additive effect against a variety of clinically important fungi. The most commonly reported adverse events with caspofungin have included fever, infusion-related reactions, headache, nausea, elevations in liver transaminase levels, and histamine-type reactions. The recommended dosage in adults is 70 mg IV on day 1 followed by 50 mg/d, with the duration of treatment depending on the severity of the patient's underlying condition and the clinical response.
CONCLUSION
Although additional studies are needed, caspofungin appears to be a promising agent for the treatment of patients with difficult-to-treat or life-threatening fungal infections.
Topics: Aged; Animals; Anti-Bacterial Agents; Antifungal Agents; Caspofungin; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Microbial; Echinocandins; Fungi; Humans; Lipopeptides; Mycoses; Peptides; Peptides, Cyclic
PubMed: 11952021
DOI: 10.1016/s0149-2918(02)85039-1 -
Expert Review of Anti-infective Therapy Apr 2013Sertaconazole is a useful antifungal agent against mycoses of the skin and mucosa, such as cutaneous, genital and oral candidiasis and tinea pedis. Its antifungal... (Review)
Review
Sertaconazole is a useful antifungal agent against mycoses of the skin and mucosa, such as cutaneous, genital and oral candidiasis and tinea pedis. Its antifungal activity is due to inhibition of the ergosterol biosynthesis and disruption of the cell wall. At higher concentrations, sertaconazole is able to bind to nonsterol lipids of the fungal cell wall, increasing the permeability and the subsequent death of fungal cells. Fungistatic and fungicidal activities on Candida are dose-dependent. The antifungal spectrum of sertaconazole includes deramophytes, Candida, Cryptococcus, Malassezia and also Aspergillus, Scedosporium and Scopulariopsis. Sertaconazole also shows an antimicrobial activity against streptococci, staphylococci and protozoa (Trichomonas). In clinical trials including patients with vulvovaginal candidiasis, a single dose of sertaconazole produced a higher cure rate compared with other topical azoles such as econazole and clotrimazole, in shorter periods. Sertaconazole has shown an anti-inflammatory effect that is very useful for the relief of unpleasant symptoms.
Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Imidazoles; Microbial Sensitivity Tests; Staphylococcal Skin Infections; Streptococcal Infections; Thiophenes
PubMed: 23566144
DOI: 10.1586/eri.13.17 -
Journal of Chromatography. B,... Jan 2022Treatment of invasive fungal infections with Caspofungin is used as the first-line antifungal agents. The minimum inhibitory concentration value is a test which...
Treatment of invasive fungal infections with Caspofungin is used as the first-line antifungal agents. The minimum inhibitory concentration value is a test which indicates the degree of sensitivity of a strain regarding a drug. However, no value of minimum inhibitory concentration for caspofungin is available because very variable value is obtained. In this work, we study the link with the adsorption phenomenon of CSF previously described in literature and the lack of minimum inhibitory concentration value. A systematic study of the impact of different parameters on CSF adsorption is reported. The effect of the nature of container material, the aqueous solution pH and the organic solvent proportion was studied. In addition, the possibility of using a coating agent to minimize the adsorption was assayed and evaluated. Results obtained showed the importance of the material used during the manipulation of CSF. The use of acidic pH aqueous solution or the addition of acetonitrile or methanol proportions (50 % and 70 %, respectively) were found efficient to avoid adsorption of CSF on glassware material, which is the relevant strategy for analytical samples of caspofungin. The treatment of HPLC glass vials and 96-well plates with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane reduced the adsorption. The significant adsorption observed in this work especially with plastic materials, questions the results obtained before in different assays and explained the absence of MIC value.
Topics: Adsorption; Antifungal Agents; Caspofungin; Chromatography, High Pressure Liquid; Glass; Microbial Sensitivity Tests; Plastics
PubMed: 34847516
DOI: 10.1016/j.jchromb.2021.123060 -
Advanced Drug Delivery Reviews Aug 2023Nystatin is an antifungal molecule with a remarkable yet squandered versatility. In this review, its mechanism of action is explored, along with its extensive action... (Review)
Review
Nystatin is an antifungal molecule with a remarkable yet squandered versatility. In this review, its mechanism of action is explored, along with its extensive action spectrum and toxicity. A multitude of methodologies to tackle the drug's physical and chemical hurdles are outlined along with some proven-effective strategies to increase its activity and/or decrease its toxicity. A separate detailed section focused on micro and nanotechnology solutions addresses new drug delivery systems made of polymeric, metallic or lipid materials. Although the topical route depicts greater representativeness amongst these formulations, the intravenous, dental, oral, vaginal and inhalation routes are also mentioned. The unsuccessful previous attempts at developing parenteral formulations of nystatin or even the withdrawal of a nystatin-loaded multilamellar liposome should not divert research away from this drug. In fact, the interest in nystatin ought to be reawakened with the ongoing clinical trials on the promising nystatin-like genetically engineered derivate BSG005.
Topics: Humans; Antifungal Agents; Nystatin; Liposomes; Drug Delivery Systems; Polymers
PubMed: 37348678
DOI: 10.1016/j.addr.2023.114969 -
Clinical Infectious Diseases : An... Mar 2003Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either... (Review)
Review
Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; Candida; Dermatitis; Drug Interactions; Exanthema; Humans; Liver; Microbial Sensitivity Tests; Pyrimidines; Triazoles; Voriconazole
PubMed: 12594645
DOI: 10.1086/367933 -
Frontiers in Cellular and Infection... 2019There are only few drugs available to treat fungal infections, and the lack of new antifungals, along with the emergence of drug-resistant strains, results in millions...
There are only few drugs available to treat fungal infections, and the lack of new antifungals, along with the emergence of drug-resistant strains, results in millions of deaths/year. An unconventional approach to fight microbial infection is to exploit nutritional vulnerabilities of microorganism metabolism. The metal gallium can disrupt iron metabolism in bacteria and cancer cells, but it has not been tested against fungal pathogens such as and . Here, we investigate activity of gallium nitrate III [Ga(NO)] against these human pathogens, to reveal the gallium mechanism of action and understand the interaction between gallium and clinical antifungal drugs. Ga(NO) presented a fungistatic effect against azole-sensitive and -resistant strains (MIC = 32.0 mg/L) and also had a synergistic effect with caspofungin, but not with azoles and amphotericin B. Its antifungal activity seems to be reliant on iron-limiting conditions, as the presence of iron increases its MIC value and because we observed a synergistic interaction between gallium and iron chelators against . We also show that an mutant (Δ) unable to grow in the absence of iron is more susceptible to gallium, reinforcing that gallium could act by disrupting iron homeostasis. Furthermore, we demonstrate that gallium has a fungistatic effect against different species of ranging from 16.0 to 256.0 mg/L, including multidrug-resistant , and . Our findings indicate that gallium can inhibit fungal pathogens under iron-limiting conditions, showing that Ga(NO) could be a potential therapy not only against bacteria but also as an antifungal drug.
Topics: Antifungal Agents; Aspergillus fumigatus; Azoles; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Gallium; Kinetics; Microbial Sensitivity Tests
PubMed: 31921699
DOI: 10.3389/fcimb.2019.00414