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Yogeshvar N. Kalia - One of the best experts on this subject based on the ideXlab platform.
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New developments in topical Antifungal Therapy
American Journal of Drug Delivery, 2006Co-Authors: Majdeline Robert, Yogeshvar N. KaliaAbstract:Superficial fungal infections are among the most widespread diseases known to man. They target parts of the body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the vagina. Fungistatic azole drugs, that is, imidazole- and triazole-containing compounds (e.g. miconazole and itraconazole, respectively), have been the mainstay of Antifungal Therapy for many years. The polyene nystatin is effective in treating Candida infections but is inactive against cutaneous dermatophytes. The advent of the fungicidal allylamines (e.g. terbinafine) and their congeners (e.g. butenafine) has improved treatment options: the course of Therapy is shorter and cure rates higher with fungicidal drugs. Other newer agents include the echinocandins (e.g. caspofungin) that are primarily intended for systemic administration but which may have a role in topical Therapy. In order to elicit a pharmacologic response following topical administration, these agents must enter into and diffuse across the target biologic tissues, which have distinct architectures and compositions depending on their function. The rate and extent of transport will depend on the interplay between the drug’s molecular properties and the characteristics of the biologic tissue. The drug may also interact with specific proteins or other membrane components. These interactions can prolong residence time and therapeutic effect; for example, azoles have an affinity for keratin (as do dermatophytes, their therapeutic target). Drug properties that increase permeability across a given membrane may render the molecule less effective at another biologic tissue; for example, the stratum corneum is a lipidic barrier, whereas the keratin-rich nail contains 10-fold less lipid and is perhaps best viewed as a hydrogel with very low lipid content. Consequently, both offer very different environments and drug delivery challenges compared with the oral and vaginal mucosae. In light of this, it is clear that formulation design and optimization are key steps in increasing the therapeutic efficacy of topical Antifungal Therapy. Furthermore, the formulation, which is the primary interface with the membrane, must not only be optimized with respect to the drug but also be compatible with the biologic tissue. Thus, developing effective formulations for topical Therapy is a complex task. In this review, we provide a brief description of newer approaches in topical Antifungal drug development and present a survey of recent work.
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New developments in topical Antifungal Therapy
American Journal of Drug Delivery, 2006Co-Authors: Majdeline El Mahrab Robert, Yogeshvar N. KaliaAbstract:Superficial fungal infections are among the most widespread diseases known to man. They target parts of the body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the vagina. Fungistatic azole drugs, that is, imidazole- and triazole-containing compounds (e.g. miconazole and itraconazole, respectively), have been the mainstay of Antifungal Therapy for many years. The polyene nystatin is effective in treating Candida infections but is inactive against cutaneous dermatophytes. The advent of the fungicidal allylamines (e.g. terbinafine) and their congeners (e.g. butenafine) has improved treatment options: the course of Therapy is shorter and cure rates higher with fungicidal drugs. Other newer agents include the echinocandins (e.g. caspofungin) that are primarily intended for systemic administration but which may have a role in topical Therapy.
I. Raad - One of the best experts on this subject based on the ideXlab platform.
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Sinus surgery combined with Antifungal Therapy is effective in the treatment of invasive Aspergillus sinusitis in neutropenic patients with cancer.
Infection, 2008Co-Authors: Ray Y Hachem, Maha Boktour, Hend Hanna, Rola Husni, Ehab Y. Hanna, Xavier M. Keutgen, B. Shukrallah, I. RaadAbstract:Background: Invasive Aspergillus sinusitis (IAS) is associated with high mortality and poor response to Antifungal Therapy in patients with hematologic malignancies (HM). Patients and Methods: We identified 353 patients with invasive aspergillosis of whom 39 patients had IAS. Of the 39 patients, 13 underwent sinus surgery (SS) in addition to the Antifungal Therapy, and the remaining 26 control patients received Antifungal Therapy alone. Most patients with IAS had underlying leukemia (85%). Both groups had comparable clinical characteristics such as gender, age, underlying disease, neutropenia at the onset, persistent neutropenia, graft-vs-host-disease, and comparable Antifungal Therapy. Results: Overall response was 7 (53.2%) in the SS group vs 5 (19.2%) in the control group (p = 0.06). Among the subgroup of patients with neutropenia at the onset of infection, the response rate in the SS group was significantly better than in the non-SS group (57% vs 11.8%, respectively; p = 0.028). Conclusion: In neutropenic patients with IAS and underlying HM, SS significantly improved the response to Antifungal Therapy. Additional studies are warranted. Infection 2008 DOI 10.1007/s15010-008-7388-5
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high dose caspofungin combination Antifungal Therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation
Bone Marrow Transplantation, 2007Co-Authors: Amar Safdar, Gilhen Rodriguez, Kenneth V I Rolston, Susan Obrien, Issa F Khouri, E J Shpall, Michael J Keating, Hagop M Kantarjian, Richard E Champlin, I. RaadAbstract:High-dose caspofungin combination Antifungal Therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation
Marin H. Kollef - One of the best experts on this subject based on the ideXlab platform.
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Effects of empiric Antifungal Therapy for septic shock on time to appropriate Therapy for Candida infection: a pilot study.
Clinical therapeutics, 2014Co-Authors: Scott T. Micek, Heather Arnold, Paul Juang, Nicholas Hampton, Matthew Mckenzie, Michael Scolarici, Marin H. KollefAbstract:Abstract Purpose Inappropriate initial Therapy for Candida -related septic shock is common and associated with a high mortality rate. This before-after pilot study was conducted to determine the feasibility of using empiric Therapy for reducing the time to appropriate Antifungal Therapy in patients with Candida -related septic shock. Methods Patients aged 18–99years with septic shock presenting to Barnes-Jewish Hospital, St. Louis, Missouri, in 2012–2013 were assigned to 1 of 2 groups. Patients presenting between January 1, 2012, and December 31, 2012, were managed according to local standard of care for patients with septic shock, to include Antifungal Therapy at the discretion of the treating physician (standard Therapy group). Patients presenting between January 1, 2013, and December 31, 2013, received empiric Antifungal Therapy (primarily micafungin 100 mg/d or fluconazole 800 mg on day 1, followed by 400 mg/d), facilitated by a clinical pharmacist in the medical intensive care unit, until microbiologic cultures were available to determine the cause of septic shock (empiric Therapy group). The primary outcome was time to appropriate Therapy after shock onset. Findings A total of 28 patients were enrolled (mean age, 56.3 [15.1] years [range, 30–92 years]; 16 [57.1%] men). The time to appropriate Therapy after shock onset was statistically shorter with empiric Therapy (n = 13) compared with standard Therapy (n = 15) (10.6 [15.8] vs 40.5 [26.0] hours; P = 0.001). Patients receiving empiric Therapy were more likely to have received appropriate Therapy within 12 hours (69.2% vs 6.7%; P = 0.001) and within 24 hours (76.9% vs 40.0%; P = NS) of shock onset. In an analysis to determine the number of septic shock patients needed to be treated with empiric Antifungal Therapy for 1 patient with Candida -related septic shock to receive appropriate treatment, 256 patients without Candida infection received a total of 687 doses of empiric Antifungal Therapy (mean, 2.7 doses per patient) compared with 136 patients who received 382 doses of standard Antifungal Therapy (mean, 2.8 doses per patient); the number needed to treat was 19.6. Implications The present pilot study demonstrated that the use of empiric Antifungal Therapy for Candida -related septic shock was associated with a statistically shorter time to administration of appropriate treatment. ClinicalTrials.gov identifier.
Majdeline Robert - One of the best experts on this subject based on the ideXlab platform.
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New developments in topical Antifungal Therapy
American Journal of Drug Delivery, 2006Co-Authors: Majdeline Robert, Yogeshvar N. KaliaAbstract:Superficial fungal infections are among the most widespread diseases known to man. They target parts of the body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the vagina. Fungistatic azole drugs, that is, imidazole- and triazole-containing compounds (e.g. miconazole and itraconazole, respectively), have been the mainstay of Antifungal Therapy for many years. The polyene nystatin is effective in treating Candida infections but is inactive against cutaneous dermatophytes. The advent of the fungicidal allylamines (e.g. terbinafine) and their congeners (e.g. butenafine) has improved treatment options: the course of Therapy is shorter and cure rates higher with fungicidal drugs. Other newer agents include the echinocandins (e.g. caspofungin) that are primarily intended for systemic administration but which may have a role in topical Therapy. In order to elicit a pharmacologic response following topical administration, these agents must enter into and diffuse across the target biologic tissues, which have distinct architectures and compositions depending on their function. The rate and extent of transport will depend on the interplay between the drug’s molecular properties and the characteristics of the biologic tissue. The drug may also interact with specific proteins or other membrane components. These interactions can prolong residence time and therapeutic effect; for example, azoles have an affinity for keratin (as do dermatophytes, their therapeutic target). Drug properties that increase permeability across a given membrane may render the molecule less effective at another biologic tissue; for example, the stratum corneum is a lipidic barrier, whereas the keratin-rich nail contains 10-fold less lipid and is perhaps best viewed as a hydrogel with very low lipid content. Consequently, both offer very different environments and drug delivery challenges compared with the oral and vaginal mucosae. In light of this, it is clear that formulation design and optimization are key steps in increasing the therapeutic efficacy of topical Antifungal Therapy. Furthermore, the formulation, which is the primary interface with the membrane, must not only be optimized with respect to the drug but also be compatible with the biologic tissue. Thus, developing effective formulations for topical Therapy is a complex task. In this review, we provide a brief description of newer approaches in topical Antifungal drug development and present a survey of recent work.
Roderick J. Hay - One of the best experts on this subject based on the ideXlab platform.
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Antifungal Therapy of yeast infections
Journal of the American Academy of Dermatology, 1994Co-Authors: Roderick J. HayAbstract:Candida infections of the skin and mucous membranes are common in both healthy and immunocompromised patients. Management with topical azole or polyene Therapy is generally straightforward except in immunocompromised patients with oropharyngeal infections and in Candida onychomycosis. Oral candidosis in patients with AIDS generally requires oral Therapy with fluconazole, itraconazole, or ketoconazole. Continuous suppressive Therapy carries the risk of the development of clinical tolerance or secondary drug resistance. In nail disease, oral Antifungal Therapy is appropriate except in paronychia, for which topical azole Antifungals appear to be equally effective. In any case it is important to determine whether Candida isolated from nail material is a true nail pathogen or merely colonizing the nail plate. Distal erosion of the nail plate, the presence of underlying host abnormalities such as Raynaud's disease, and hyphae in the nail plate are clues that organism is invading the nail plate.
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Risk/benefit ratio of modern Antifungal Therapy: focus on hepatic reactions.
Journal of the American Academy of Dermatology, 1993Co-Authors: Roderick J. HayAbstract:The purpose of this article is to review the risk/benefit ratio of the oral Antifungals: griseo-fulvin, ketoconazole, fluconazole, itraconazole, and terbinafine. The reported side effects of each drug have been listed with particular emphasis on the possibility of hepatic damage. All oral Antifungal agents cause minor gastrointestinal upset, as well as headache and skin reactions. There is also a rare incidence of reversible hepatic damage. Although the incidence of abnormal liver function tests from oral Antifungal Therapy is extremely low, patients should be advised to inform their physician if any warning symptoms are noticed.