Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

ABSTRACT This work describes the increased activity of a natural antifungal peptide in the presence of another antifungal peptide from a different family. This is termed antifungal synergy. Synergy is important for decreasing the amount of antifungal molecule needed to control the disease. Traditionally, naturally occurring antifungal molecules are assayed in isolation. Identification of synergistic interactions between antifungal peptides means that their activities in a complex biological system are likely to be different from what we observe when examining them individually. This study identified synergy between an antifungal peptide and a group of peptides that do not affect fungal growth in vitro. This provides the foundation for generation of transgenic plants with increased resistance to fungal disease and identification of antifungal accessory factors that enhance the activity of innate immune molecules but do not have an antifungal effect on their own. Defensins are a large family of small, cationic, cysteine-rich proteins that are part of the defense arsenal that plants use for protection against potentially damaging fungal infections. The plant defensin NaD1 from Nicotiana alata is a potent antifungal protein that inhibits growth and kills a variety of fungal pathogens that affect both plant and animal (human) hosts. Some serine protease inhibitors have also been reported to be antifungal molecules, while others have no inhibitory activity against fungi. Here we describe the synergistic activity of the plant defensin NaD1 with a selection of serine protease inhibitors against the plant pathogens Fusarium graminearum and Colletotrichum graminicola and the animal pathogen Candida albicans. The synergistic activity was not related to the protease inhibitory activity of these molecules but may arise from activation of fungal stress response pathways. The bovine pancreatic trypsin inhibitor (BPTI) displayed the most synergy with NaD1. BPTI also acted synergistically with several other antifungal molecules. The observation that NaD1 acts synergistically with protease inhibitors provides the foundation for the design of transgenic plants with improved resistance to fungal disease. It also supports the possibility of naturally occurring accessory factors that function to enhance the activity of innate immunity peptides in biological systems. IMPORTANCE This work describes the increased activity of a natural antifungal peptide in the presence of another antifungal peptide from a different family. This is termed antifungal synergy. Synergy is important for decreasing the amount of antifungal molecule needed to control the disease. Traditionally, naturally occurring antifungal molecules are assayed in isolation. Identification of synergistic interactions between antifungal peptides means that their activities in a complex biological system are likely to be different from what we observe when examining them individually. This study identified synergy between an antifungal peptide and a group of peptides that do not affect fungal growth in vitro. This provides the foundation for generation of transgenic plants with increased resistance to fungal disease and identification of antifungal accessory factors that enhance the activity of innate immune molecules but do not have an antifungal effect on their own.

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Pattern of Candida species isolated from patients with diabetes mellitus and vulvovaginal candidiasis and their response to single dose oral fluconazole therapy

Journal of Infection ◽

10.1016/j.jinf.2005.03.005 ◽

2006 ◽

Vol 52 (2) ◽

pp. 111-117 ◽

Cited By ~ 54

Author(s):

Deepti Goswami ◽

Ravinder Goswami ◽

Uma Banerjee ◽

Vatsla Dadhwal ◽

Sunita Miglani ◽

...

Keyword(s):

Diabetes Mellitus ◽

Single Dose ◽

Candida Species ◽

Vulvovaginal Candidiasis ◽

Oral Fluconazole ◽

Patients With Diabetes ◽

Dose Oral ◽

Fluconazole Therapy

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Laryngeal Cryptococcosis: An Evolving Rare Clinical Entity

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489419826131 ◽

2019 ◽

Vol 128 (5) ◽

pp. 472-479 ◽

Cited By ~ 3

Author(s):

Douglas M. Worrall ◽

David K. Lerner ◽

Matthew R. Naunheim ◽

Peak Woo

Keyword(s):

English Language ◽

Inhaled Corticosteroids ◽

Clinical Manifestations ◽

Oral Fluconazole ◽

Cryptococcal Infection ◽

Fluconazole Therapy ◽

Methenamine Silver ◽

Chronic Laryngitis ◽

Mass Lesions ◽

Antigen Testing

Objectives: Describe the demographics and clinical manifestations of laryngeal cryptococcosis. Develop a simple approach to the diagnostic workup and treatment of localized laryngeal cryptococcal infection. Methods: A new case of laryngeal cryptococcosis encountered at our institution is presented and placed in context of the literature surrounding prior reported cases. PubMed, Google Scholar, SCOPUS, and Web of Science were queried from inception to August 2018 with the terms Larynx or Laryngeal and Cryptococcosis or Cryptococcus by two independent reviewers for English-language cases of cryptococcal infection of the larynx. Results: Twenty-nine unique cases of laryngeal cryptococcosis were identified. Median age at presentation was 65 years old. All patients presented with persistent or progressive hoarseness. Lesions were predominantly on the true vocal cords (79%), 38% associated with an adherent white exudate or leukoplakia. A minority (28%) was immunocompromised, and of the remaining immunocompetent hosts, 67% were found to be using nebulized or inhaled corticosteroids (ICS) prior to infection. Diagnosis should be suspected in patients with chronic laryngitis or mass lesions with the aforementioned risk factors. Diagnosis was made by histopathology with cryptococcal yeasts identified on methenamine silver (55%) and/or mucicarmine stains (48%). Serum cryptococcal antigen testing was unreliable (sensitivity = 39%). The mainstay of effective treatment was prolonged oral Fluconazole therapy, with two cases of laser therapy ablation of residual lesions. Improvement in voice and vocal lesions varied from weeks to months. Conclusions: Laryngeal cryptococcosis is a rare cause of persistent hoarseness, which appears to be clinically evolving and more frequently affecting immunocompetent hosts chronically using nebulized or inhaled corticosteroids. Laryngeal cryptococcal infection is readily treatable with prolonged oral antifungals once biopsy and histopathological stains confirm the diagnosis.

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Oral candidiasis - Perleche Mimicking Malignancy

Community Based Medical Journal ◽

10.3329/cbmj.v3i1.53330 ◽

2014 ◽

Vol 3 (1) ◽

pp. 53-55

Author(s):

M Hasibur Rahman ◽

Md Hadiuzzaman ◽

Nahida Islam ◽

Md Shahidul Islam ◽

Sabrina Alam Mumu ◽

...

Keyword(s):

Candida Species ◽

Oral Candidiasis ◽

Healthy Individuals ◽

Oral Fluconazole ◽

Mucosal Surfaces ◽

Fluconazole Therapy ◽

P 53

Candida species inhabit the mucosal surfaces of healthy individuals. Major forms of oral candidiasis are pseudomembranous and atrophic form, but chronic hyperplastic candidiasis (CHC) is rarely seen. We encountered a case of whitish plaque with nodule and ulceration. When an intraoral nodule is observed, the possibility of CHC should be taken into consideration. Biopsy of the lesion failed to show any signs of malignancy, and patient responded well to oral fluconazole therapy only. CBMJ 2014 January: Vol. 03 No. 01 P: 53-55

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Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients

The American Journal of Medicine ◽

10.1016/s0002-9343(88)80081-0 ◽

1988 ◽

Vol 85 (4) ◽

pp. 477-480 ◽

Cited By ~ 92

Author(s):

John J. Stern ◽

Barry J. Hartman ◽

Patricia Sharkey ◽

Veronica Rowland ◽

Kathleen E. Squires ◽

...

Keyword(s):

Acquired Immunodeficiency Syndrome ◽

Oral Fluconazole ◽

Fluconazole Therapy ◽

Acquired Immunodeficiency ◽

Immunodeficiency Syndrome

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Oral fluconazole therapy for keratomycosis

Acta Ophthalmologica ◽

10.1111/j.1755-3768.1994.tb04697.x ◽

2009 ◽

Vol 72 (6) ◽

pp. 765-767 ◽

Cited By ~ 11

Author(s):

Meenakshi Thakar

Keyword(s):

Oral Fluconazole ◽

Fluconazole Therapy

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Parenteral and Oral Fluconazole for Acute Cryptococcal Meningitis in Aids: Experience with Thirteen Patients

Annals of Pharmacotherapy ◽

10.1177/106002809202600701 ◽

1992 ◽

Vol 26 (7-8) ◽

pp. 876-882 ◽

Cited By ~ 3

Author(s):

John J. Stern ◽

Nancy A. Pietroski ◽

R. Michael Buckley ◽

Michael N. Braffman ◽

Michael G. Rinaldi

Keyword(s):

Amphotericin B ◽

Cryptococcal Meningitis ◽

Initial Therapy ◽

High Rate ◽

Primary Therapy ◽

Noncomparative Trial ◽

Aids Patients ◽

Oral Fluconazole ◽

Fluconazole Therapy ◽

The Central Nervous System

OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12–16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failures and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.

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