Activity of amphotericin B, anidulafungin, caspofungin, micafungin, posaconazole, and voriconazole against Candida albicans with decreased susceptibility to fluconazole from APECED patients on long-term azole treatment of chronic mucocutaneous candidiasis

2008 ◽  
Vol 62 (2) ◽  
pp. 182-185 ◽  
Author(s):  
Riina Rautemaa ◽  
Malcolm Richardson ◽  
Michael A. Pfaller ◽  
Jaakko Perheentupa ◽  
Harri Saxén
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis

scholarly journals 149. Efficacy of Cochleated Amphotericin B (CAMB) in Mouse and Human Mucocutaneous Candidiasis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S204-S205
Author(s):  
Jigar V Desai ◽  
Amanda Urban ◽  
Doris Z Swaim ◽  
Elise Ferre ◽  
Benjamin Colton ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Improvement ◽  
Clinical Efficacy ◽  
Chronic Mucocutaneous Candidiasis ◽  
Vaginal Tissue ◽  
Dose Escalation Study ◽  
Fungal Burden ◽  
Mucocutaneous Candidiasis ◽  
Inherited Susceptibility

Abstract Background Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC), often requiring long-term azole-based treatment. Due to increasing azole resistance, alternative treatments are desirable. Acquired resistance to amphotericin B (AMB) is rare but AMB use is limited by parenteral administration and nephrotoxicity. Cochleated AMB (CAMB) is a new oral formulation of AMB and thus an attractive option for oropharyngeal candidiasis (OPC), esophageal candidiasis (EC) and vulvovaginal candidiasis (VVC). We assessed the efficacy of CAMB in mouse models of OPC and VVC and in 4 patients with azole resistant CMC manifesting as OPC, EC or VVC. Methods Act1 -/- mice were infected with C. albicans in models of OPC and VVC and were treated once daily via oral gavage with CAMB or vehicle or intraperitoneal AMB-deoxycholate (AMBd) from day 1 through 4 post-infection (pi). At day 5 pi, the tongue or vaginal tissue was harvested to quantify fungal burden. Patients with azole resistant CMC enrolled in a phase 2A CAMB dose escalation study. The primary endpoint was clinical improvement at 2 weeks based on an efficacy scale, followed by optional extension for long-term suppression of CMC to assess safety and efficacy. Results CAMB-treated mice had significantly reduced tongue and vaginal tissue fungal burden compared to vehicle-treated mice, while they exhibited comparable fungal control relative to AMBd-treated mice. Among 4 CAMB-treated patients, 3 reached clinical efficacy by 2 weeks at a dose of 400 mg twice daily and one reached clinical efficacy at 200 mg twice daily. Three of 4 patients continued on the extension phase past 48 months with sustained clinical improvement of OPC and EC; patient #3 had relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical response was not seen for onychomycosis or VVC. CAMB was safe and well-tolerated without renal toxicity. Conclusion Oral administration of CAMB in IL-17-signaling deficient mice resulted in reduced tongue and vaginal tissue fungal burden during mucosal C. albicans infections. A proof-of-concept clinical trial in humans with inherited CMC showed efficacy in OPC and EC with good tolerability and safety. Disclosures Benjamin Colton, PharmD, Merck (Shareholder)Pfizer (Shareholder) Ruying Lu, n/a, Matinas BioPharma Inc. (Employee)Matinas BioPharma Inc. (Employee, Shareholder) Theresa Matkovits, PhD, Matinas BioPharma (Employee, Shareholder) Raphael J. Mannino, n/a, Matinas BioPharma Inc. (Employee, Shareholder) Michail Lionakis, MD, ScD, Matinas BioPharma (Research Grant or Support)

Candida Esophagitis and Laryngitis in Chronic Mucocutaneous Candidiasis

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 380-384
Author(s):  
Roger H. Kobayashi ◽  
Howard M. Rosenblatt ◽  
Jean M. Carney ◽  
William J. Byrne ◽  
Marvin E. Ament ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Topical Therapy ◽  
Signs And Symptoms ◽  
Poor Correlation ◽  
Chronic Mucocutaneous Candidiasis ◽  
Oral Lesions ◽  
Mucocutaneous Candidiasis ◽  
Left Mainstem ◽  
Repeat Endoscopy ◽  
Intravenous Amphotericin

Five children (aged 11 to 19 years) with lifelong chronic mucocutaneous candidiasis had 12 episodes of esophageal and/or laryngeal candidiasis documented by endoscopy. Symptoms included hoarseness (8/12), dysphagia (6/12), and hemoptysis (1/12). There was poor correlation between oral lesions and esophageal or laryngeal involvement. On fiberoptic endoscopy, the esophagus was involved alone in four episodes (33%), the larynx in two episodes (17%), and both structures in six episodes (50%). In six of eight instances, the esophagram was nondiagnostic or markedly underestimated the extent of inflammation. Intravenous amphotericin B or miconazole resulted in the resolution of these infections for variable periods of time. Repeat endoscopy was used to follow the course of the disease. Aerosolized amphotericin B was effective on one occasion in clearing candidal lesions of the larynx and one small area of the left mainstem bronchus. Oral topical therapy was not beneficial. Since the signs and symptoms of laryngitis or esophagitis are often minimal or absent and complications, including strictures, may arise from chronic inflammation, periodic endoscopy and systemic therapy may be necessary.

TREATMENT OF MUCOCUTANEOUS CANDIDIASIS WITH TRANSFER FACTOR

PEDIATRICS ◽  
1974 ◽  
Vol 53 (1) ◽  
pp. 63-70
Author(s):  
Ralph D. Feigin ◽  
Penelope G. Shackelford ◽  
Seth Eisen ◽  
Lynn E. Spitler ◽  
Larry K. Pickering ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Skin Test ◽  
Migration Inhibitory Factor ◽  
Transfer Factor ◽  
Chronic Mucocutaneous Candidiasis ◽  
Myeloperoxidase Activity ◽  
Mucocutaneous Candidiasis ◽  
Receptor Sites ◽  
Stimulation Of

Evaluation of a patient with chronic mucocutaneous candidiasis revealed that the patient lacked delayed hypersensitivity to candida and other skin test antigens and the patient's lymphocytes could not be stimulated in vitro with candida antigen. Phytohemagglutinin stimulation of lymphocytes in vitro was normal. Candidacidal function and myeloperoxidase activity of the patient's leukocytes were normal. The patient's lymphocytes produced migration inhibitory factor in response to candida antigen and the monocyte receptor sites for IgG were intact. Repeated treatments with amphotericin B, alone or with 5-fluorocytosine, were followed by immediate relapse. Four doses of transfer factor were administered and when coupled with amphotericin B on two occasions prompted remissions of 6 and 4 months, respectively.

Laryngeal Candidiasis Presenting as Inspiratory Stridor

PEDIATRICS ◽  
1982 ◽  
Vol 69 (2) ◽  
pp. 234-236
Author(s):  
Richard F. Jacobs ◽  
Kyle Yasuda ◽  
Arnold L. Smith ◽  
Denis R. Benjamin
Keyword(s):  
Candida Albicans ◽  
Vocal Cord Paralysis ◽  
Upper Airway ◽  
Neonatal Infection ◽  
Chronic Mucocutaneous Candidiasis ◽  
Inspiratory Stridor ◽  
Mucocutaneous Candidiasis ◽  
Initial Symptoms ◽  
Candida Albicans Infection ◽  
Laryngeal Involvement

In 1970, Perrone1 first reported laryngeal obstruction secondary to Candida albicans infection in a newborn. There have been several descriptions of congenital or neonatal infection with C albicans including pustubar dermatitis,2 pneumonia,3 meningitis, and arthritis.4 However, none of these reports noted laryngeal involvement. Recently, laryngitis and esophagitis were described in children with chronic mucocutaneous candidiasis.5 Adult patients predisposed to invasive candidal infections have had laryngeal involvement; on occasion their initial symptoms were those of upper airway obstruction.6 Infants and newborns with inspiratory stridor are usually evaluated for laryngomalacia, congenital subglottic stenosis, or vocal cord paralysis. Candidal laryngitis presenting as inspiratory stridor has not been well documented in the pediatric literature.

scholarly journals Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines

2010 ◽  
Vol 207 (2) ◽  
pp. 299-308 ◽  
Author(s):  
Kai Kisand ◽  
Anette S. Bøe Wolff ◽  
Katarina Trebušak Podkrajšek ◽  
Liina Tserel ◽  
Maire Link ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Tolerance Induction ◽  
Chronic Mucocutaneous Candidiasis ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrine Syndrome ◽  
Self Tolerance ◽  
Multicenter Survey ◽  
Autoimmune Polyendocrinopathy ◽  
Patient Groups ◽  
Endocrine Features

Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.

CHRONIC MUCOCUTANEOUS CANDIDIASIS—ASSOCIATED IMMUNOLOGIC ABNORMALITIES

PEDIATRICS ◽  
1968 ◽  
Vol 42 (2) ◽  
pp. 227-230
Author(s):  
Joseph W. Landau
Keyword(s):  
Candida Albicans ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Etiologic Agent ◽  
Chronic Mucocutaneous Candidiasis ◽  
Internal Organs ◽  
Predisposing Factor ◽  
Mucocutaneous Candidiasis ◽  
Mucous Membranes ◽  
Systemic Infections

Candidiasis (moniliasis, candidosis) includes a group of fungous diseases varying in severity from commonly encountered local superficial involvement of the oral mucosa to fulminating systemic infections rapidly terminating in death.1 The etiologic agent is Candida albicans or occasionally another species of candida. These fungi are frequently found as saprophytes in the oral cavity, gastrointestinal tract, and vaginal area. Some local or systemic impairment of host defense mechanisms usually appears to be an essential predisposing factor for the development of candidiasis. The term chronic mucocutaneous candidiasis refers to a heterogeneous group of fungous diseases characterized by persistent or recurrent candida infection of mucous membranes, nails, and skin.1-3 Involvement of internal organs seldom, if ever, occurs.

Sign in / Sign up

Export Citation Format

Share Document