Topical Antifungal Treatment Research Articles

Anogenitale Pilzerkrankungen

Mycotic infections of the anogenital region are very common in dermatological practice. While dermatophyte infections are more frequent in men, genital candidosis is a more striking problem in women. The increasing prevalence of non-albicans species (esp. C. glabrata, C. krusei, C. guilliermondii) with their resistance against azole derivatives may be responsible for therapeutic failures and a relapsing course in some instances. Most superficial infections of the anogenital area respond satisfactorily to topical antifungal treatment, especially if provocative factors and the possibility of sexual transmission are considered. Systemic treatment is recommended in cases of widespread dermatophyte infections, candidosis or systemic mycosis.

Role of fungus in eosinophilic sinusitis

Chronic rhinosinusitis is characterized by a broad diagnostic and etiologic spectrum. It has been postulated that fungal organisms might represent the immunologic target initiating and maintaining the disease process in patients with chronic rhinosinusitis as a common denominator. This review analyzes the available data to describe the current understanding of the role of fungus in the pathophysiology of chronic rhinosinusitis. Recent findings have demonstrated that using highly sensitive methods, the detection rate of fungi in nasal mucin can be increased to approximately 100% in patients and in healthy controls. If this ubiquitous fungal contamination were to be related to a causative mechanism in chronic rhinosinusitis, there would have to be an immunologic sensitization in patients in contrast with healthy individuals, which is yet not fully understood. However, studies were able to demonstrate cytokine production in blood-derived lymphocytes in the presence of fungi in patients, but not in healthy controls. Several questions arise. If this is a relevant finding, in what percentage of chronic rhinosinusitis patients could it be causative? Is chronic rhinosinusitis, then, a systemic disease? How is the extramucosal target in the mucin presented to the immune system? Is intranasal, topical antifungal treatment a successful option? The role of fungal organisms in the etiology of eosinophilic rhinosinusitis is reviewed with respect to novel findings, and arising questions are discussed in the light of recent investigations.

What's Your Diagnosis? Well-Demarcated Vulvar Erythema in Two Girls

A 3-year-old girl has a persistent vulvar rash which has not responded to topical antifungal treatment. The rash is erythematous well-demarcated and symmetrical. She has had no vaginal discharge. An 11-year-old girl is seeing you for a vulvar rash which she has had for months. Her rash is erythematous well-demarcated and symmetrical with a small amount of scale at the periphery. She too has not had vaginal discharge. (excerpt)

Effects of topical Amphotericin B on expression of cytokines in nasal polyps

Objective—Although chronic rhinosinusitis (CRS) is one of the most frequently reported chronic diseases its etiology is not well understood. Recently, fungi have been proposed to influence the chronicity of rhinosinusitis. If fungi do play an important role then topical antifungal treatment may improve the inflammatory process of CRS. Therefore, in this study we measured inflammatory cytokine levels in nasal polyps after intranasal antifungal irrigation.Material and Methods—Nasal polyps were collected before and 4 weeks after treatment with 100 mg/l topical amphotericin B (n=16), 50 mg/l topical amphotericin B (n=14) or normal saline (n=11). The cytokine—IL-5, IL-8, interferon-γ, RANTES—protein content of polyp homogenates were determined by means of ELISA.Results—Nasal polyps were found to contain large amounts of cytokines (IL-5, IL-8 and RANTES) compared with normal inferior turbinates. After 4 weeks of treatment with topical agents, IL-5 levels tended to decrease in comparison with those of the other cytokines, but this difference was not statistically significant.Conclusions—Topical amphotericin B treatment and nasal saline irrigation both influence the expression of nasal polyp cytokines. Topical nasal irrigation may influence the inflammatory process of CRS.

Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: A randomized, double-blind clinical trial

Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported. The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial. Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques. Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups. Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.

Topical antifungal treatment cures exit-site fungal infection

Exit-site fungal infection, although rarely reported, may be a critical complication in patients on peritoneal dialysis. There is no optimal treatment of exit-site fungal infection. We report four cases of exit-site infection with Candida parapsilosis. Four-week treatment with topical sulconazole cream was administered. Fungal infection was cured in all patients but followed by exit-site bacterial infection in two patients. The topical application of sulconazole cream is recommended for exit-site fungal infection. © 2002 by the National Kidney Foundation, Inc.

Lamellar keratoplasty for the treatment of fungal keratitis.

To determine the therapeutic value of lamellar keratoplasty (LKP) in the treatment of fungal keratitis not curable by antifungal chemotherapy. Fifty-five patients, in whom a diagnosis of fungal keratitis was confirmed by microscopic analysis of corneal scrapings or confocal microscopy, and who were not cured by topical and oral antifungal medication, were given LKP. After LKP, topical antifungal treatment was continued for 2 weeks with gradual tapering of the drugs. The excised recipient lamella was used for microbial culture and histopathologic examination. Therapeutically beneficial results were achieved in 51 cases (92.7%) of the 55 LKPs that were performed. In these 51 cases, there was no recurrence of infection, and the resulting visual acuity ranged from 20/63 to 20/20. Patient follow-up ranged from 6 to 18 months. In four cases (7.3%), there was a recurrence of the fungal infection within 2 weeks of LKP. In these four patients, the infection was cured by performing a penetrating keratoplasty (PKP). Forty-six of the recipient lamellae were culture positive for fungi. Thirty-three of these cultures were identified as Fusarium, six as Aspergillus, three as Candida, one as Penicillium species, and in the other three cases, unidentified septate hyphae were noted. In the four cases of recurrent infection, microbiologic culture revealed three cases with Fusarium species and one case with Aspergillus species. Histopathologic analysis of periodic acid-Schiff (PAS)-stained tissue sections of donor lamellae revealed fungal filaments in all samples. Immune reactions to the lamellar grafts were not observed and the donor lamellae remained clear for the duration of follow-up. Lamellar keratoplasty can be effective for treating fungal keratitis that is not cured by antifungal therapeutics. In addition, LKP can provide useful vision with few complications. Furthermore, corneal tissue used in LKP may be obtained more easily than healthy tissue used in PKP.

Oral hairy leukoplakia in a child with AIDS

A case of a 9-year-old boy with AIDS and severe hairy leukoplakia on the tongue is reported. Clinically it appears as a bilateral whitish-grey, nonremovable lesion on the lateral margins of the tongue with characteristic vertical corrugations. The lesion failed to respond to topical and systemic antifungal treatment. In contrast, it completely disappeared after treatment with 600 mg acyclovir per day for 1 month. During the hairy leukoplakia development the CD4-lymphocytes count was 95/microL.

Liposomal amphotericin-B (AmBisome) for treatment of cutaneous widespread candidosis in an infant with methylmalonic acidaemia

In a 10-week-old infant with vitamin B12-unresponsive methylmalonic acidaemia, cutaneous candidosis (Candida albicans) progressed rapidly despite topical antifungal treatment. After 1 week of intravenous therapy with liposomal amphotericin-B (AmBisome) the dermatitis disappeared completely and blood cultures were sterile. No side-effects were observed. This is one of the first experiences in the treatment of infants with this new antifungal agent.

Nipple Pain, Mastalgia and Candidiasis in the Lactating Breast

EDITORIAL COMMENT: We accepted this paper for publication because we thought it would interest readers and probably help their patients. The authors did not obtain confirmatory evidence of infection with Candida in Case 2 which is a pity, especially as the condition did not respond rapidly to nystatin and gentian violet. The editorial committee does not endorse the comments regarding the usefulness of dietary measures in the control of candidiasis. We would be interested to publish a study of a larger series of lactating women with these symptoms, with bacteriological diagnosis, and treatment by a single antifungal agent if C. albicans is isolated. Since the patients took so long to respond to treatment, it could be that an orally active antifungal agent would achieve a superior therapeutic result. Author's response: Itmay well be that an orally active antifungal agent would achieve a superior therapeutic result, but the only such agent available in Australia at present is ketoconazole which is excreted in breast milk and is not recommended for use in lactating mothers. It is also contraindicated in pregnancy because it is teratogenic, and use in children is not recommended according to the manufacturers, as stated in MIMS 1991. Thus, we are limited to using nystatin as an oral agent in mothers or infants, or miconazole gel as a topical treatment for oral candidiasis in the infant; nystatin is not absorbed into the blood stream or excreted in breast milk, and the status of miconazole in relation to lactation is not understood, although it is considered safe even for newborn infants. There is also some difficulty in avoiding use of gentian violet as a topical nipple treatment in nipple thrush because we have experienced some degree of sensitivity to nystatin, miconazole and clotrimazole creams or ointments, probably due to the vehicle rather than the therapeutic agent. This is why we have decided to slay with gentian violet, fully aware of the animal studies which suggest it to be carcinogenic in mice; we have not found any allergic reactions in over 300 users. Thus, a study in which only one antifungal agent was used might be difficult to set up since application of some antifungal substance to the nipple seems necessary to clear symptoms. We think that we are dealing with a condition which usually develops over a period of several weeks, and which may need a similar time to resolve. Summary: During lactation, persistently sore nipples or shooting breast pain in the absence of local or systemic signs may be symptoms of C. albicans infection of the nipples and/or breast ducts. The nipple may be erythematous or fissured, but the appearance does not resemble oral or vaginal candidiasis. Case 1 is a woman with sore nipples following a course of antibiotics. Case 2 is a woman with severe shooting breast pain which was worsened by antibiotic treatment. Treatment included topical and oral antifungal treatment for the mother in conjunction with an ‘anti-candida’ diet. The infant's mouth was also treated to prevent reinfection.

Is tinea unguium still widely incurable? A review three decades after the introduction of griseofulvin

<h3>• Background.—</h3> Tinea unguium, especially of the feet, for ages has been looked on as an incurable disease. Today, therapeutic outcome is still controversial. To evaluate the present state of antifungal therapy of dermatophytoses of the nails, a survey of the pertinent literature has been performed. <h3>Observations.—</h3> The introduction of griseofulvin three decades ago was first considered a major breakthrough. Today, however, conventional griseofulvin treatment regimens must be called disappointing in terms of clinical and microbiological cure to be achieved. Cure rates of 40% to 100% have been reported for fingernail infections, but only 3% to 38% for toenail tinea. Microbiological cure rates look only slightly better. Limited experience suggests that additional measures such as surgical nail avulsion or topical antifungal treatment might improve therapeutic outcome. Toenail avulsion increases cure rates to 47% to 82%. The lack of an adequate follow up, however, makes all statements questionable. <h3>Conclusions.—</h3> Results are only limited with respect to newly developed oral antifungal agents. Whereas ketoconazole treatment had to be omitted due to its hepatotoxic effect, its congener, intraconazole, is under investigation. High cure rates have been obtained in a preliminary study with oral terbinafine, 0.25 g/d, for 12 months, which have cleared toenail tinea in 15 of 17 patients. The value of topical treatment alone has not yet been definitely established. The application of a topical azole (bifonazole) in combination with chemical nail avulsion, using urea paste under occlusion, has resulted in negative cultures in 62% of the patients 3 months after the end of treatment. (<i>Arch Dermatol.</i>1992;128:243-248)

Is Tinea Unguium Still Widely Incurable?

Tinea unguium, especially of the feet, for ages has been looked on as an incurable disease. Today, therapeutic outcome is still controversial. To evaluate the present state of antifungal therapy of dermatophytoses of the nails, a survey of the pertinent literature has been performed. The introduction of griseofulvin three decades ago was first considered a major breakthrough. Today, however, conventional griseofulvin treatment regimens must be called disappointing in terms of clinical and microbiological cure to be achieved. Cure rates of 40% to 100% have been reported for fingernail infections, but only 3% to 38% for toenail tinea. Microbiological cure rates look only slightly better. Limited experience suggests that additional measures such as surgical nail avulsion or topical antifungal treatment might improve therapeutic outcome. Toenail avulsion increases cure rates to 47% to 82%. The lack of an adequate follow up, however, makes all statements questionable. Results are only limited with respect to newly developed oral antifungal agents. Whereas ketoconazole treatment had to be omitted due to its hepatotoxic effect, its congener, intraconazole, is under investigation. High cure rates have been obtained in a preliminary study with oral terbinafine, 0.25 g/d, for 12 months, which have cleared toenail tinea in 15 of 17 patients. The value of topical treatment alone has not yet been definitely established. The application of a topical azole (bifonazole) in combination with chemical nail avulsion, using urea paste under occlusion, has resulted in negative cultures in 62% of the patients 3 months after the end of treatment.

Nipple Pain, Mastalgia and Candidiasis in the Lactating Breast

During lactation, persistently sore nipples or shooting breast pain in the absence of local or systemic signs may be symptoms of C. albicans infection of the nipples and/or breast ducts. The nipple may be erythematous or fissured, but the appearance does not resemble oral or vaginal candidiasis. Case 1 is a woman with sore nipples following a course of antibiotics. Case 2 is a woman with severe shooting breast pain which was worsened by antibiotic treatment. Treatment included topical and oral antifungal treatment for the mother in conjunction with an 'anti-candida' diet. The infant's mouth was also treated to prevent reinfection.

Oral, Topical and Parenteral Antifungal Treatment with Itraconazole in Normal and in Immunocompromised Animals

Itraconazole was dissolved in polyethylene glycol for oral and topical treatment and in hydroxypropyl-beta-cyclodextrin for oral, topical or parenteral treatment. Topical and oral treatment was successful in microsporosis, trichophytosis, skin-and vaginal candidosis, pityrosporosis and eye mycosis by Candida, Fusarium and Aspergillus. Vaginal candidosis could be cured with a one-day topical or oral treatment. The same results could not be obtained with any of the reference compounds (griseofulvin, terbinafine, ketoconazole or fluconazole) on a mg per kg body weight base, nor on a % concentration base. Antifungal levels were determined by bioassay: biologically active antifungal levels were present in plasma and vaginal fluid of rats, after one oral dose of 10 mg.kg-1, for at least 72 and 96 hours respectively. This was in good correlation with findings on prophylaxis of vaginal candidosis. Itraconazole was also successfully used, in normal animals and animals immunodepressed with various agents, in disseminated and systemic diseases: trichophytosis, sporotrichosis, histoplasmosis, candidosis, aspergillosis and cryptococcosis. Oral and parenteral treatment with itraconazole was compared in various models to oral and parenteral fluconazole and to parenteral amphotericin B. The outcome with itraconazole was better than with the other antifungals. Meningeal cryptococcosis responded very well to itraconazole. Combination therapy of itraconazole and fluconazole was not superior to treatment with itraconazole alone. No side-effects were observed in relation to itraconazole treatment.

Oral candidiasis in Sjögren's syndrome: Prevalence, clinical correlations, and treatment

Red, nonulcerated, uncomfortable oral mucosal lesions that are often thought to be caused by chronic xerostomia develop in some patients with Sjögren's syndrome (SS). However, we find that these lesions (1) clinically resemble chronic atrophic candidiasis (CAC), (2) usually yield Candida species from their surface, and (3) can be eliminated by topical antifungal drugs in spite of continuing xerostomia. In 246 patients who had primary or secondary SS, we correlated the presence or absence of atrophic oral mucosal lesions with the patient's salivary function and other clinical features. The 91 patients (37%) who had these lesions were older, had a greater frequency of primary SS and of oral symptoms, had had oral symptoms for a longer period, had more salivary gland inflammation, and had lower stimulated parotid flow rates than the 155 patients without CAC ( p < 0.05). However, unstimulated whole salivary flow rates and denture status were not significantly different. Topical antifungal treatment, begun on 47 patients, eliminated lesions in some. The methods of treating CAC are discussed. Candida-associated oral mucosal lesions do not develop in all patients with SS, but in susceptible patients, SS leads to a reversible form of CAC that is not associated with dentures.

Chronic mucocutaneous candidiasis

The pathogenesis of chronic mucocutaneous candidiasis is surveyed. Treatment comprises topical antifungal treatment which is insufficient, systemic antifungal treatment which is often followed by a rapid relapse, and specific immunotherapy with live tissue or transfer factor. Combination of systemic antifungal therapy and immunotherapy seems to be the most promising approach. However, no permanent cure has so far been achieved.

Efficacy of Topical Antifungal Treatment in Denture Stomatitis

Summary: The report presents results of treatment of 90 patients with denture stomatitis, comprising cases with mycologically controlled yeast-like fungal infections. Pimafucin drops were applied in form of a suspension dropped onto the adjacent denture surface. After a 3-week treatment, 85 per cent of the cases revealed complete recovery, while 11 per cent demonstrated significantly improved clinical state. The results of control mycological examinations after treatment were negative in 80 per cent of the cases. Zusammenfassung: Bei 90 Kranken mit der klinischen Diagnose Stomatitis prothetica und mykologisch nachgewiesener Anwesenheit von hefeähnlichen Pilzen, wurden „Pimafucin drops” in Suspensionsform angewandt. Das Präparat wurde auf die der Schleimhaut anliegenden Oberfläche der Prothesenplatte aufgetragen. Nach einer 3-Wochen-Kur wurde bei 85% Kranken Heilung und bei weiteren 11% weitgehende klinische Besserung festgestellt. Mykologische Kontrollen waren in 80% der Fälle negativ.