No abstract

We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35°C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective.Dermatophytes are a specialized group of fungi which affect keratinous tissue of humans and of other vertebrates, causing superficial infections. In recent years the number of infections caused by these fungi has increased considerably (7, 15), causing particular concern when they infect immunocompromised patients where atypical manifestations and more severe, extensive lesions can be produced (1,14). Dermatophytoses generally respond well to topical antifungal therapy, although local therapy may be inappropriate for extensive infections or for infections affecting the nails or scalp. In recent years, a number of safe and highly effective antifungal agents have been introduced into clinical practice. Among them, terbinafine (TF), itraconazole (ITZ), fluconazole (FCZ), and more recently, voriconazole (VCZ) and the new triazole UR-9825, still under clinical investigation, are probably the most promising. However, their activity against significant number of strains, representing a wide spectrum of dermatophyte species and following standard procedures, has not yet been investigated. Consequently, the aim of this study has been to evaluate the in vitro activity of the traditionally available antifungal drugs and of some of the newer ones against a significant number of strains of dermatophytes by following mainly the NCCLS guidelines for testing filamentous fungi (11). MATERIALS AND METHODS Strains.A total of 508 strains of dermatophytes belonging to 24 species were tested. They were Epidermophyton floccosum (n ϭ 22), Microsporum audouinii (n ϭ 8), Microsporum canis (n ϭ 105), Microsporum cookei (n ϭ 1), Microsporum ferrugineum (n ϭ 4), Microsporum fulvum (n ϭ 1), Microsporum gallinae (n ϭ 1), Microsporum gypseum (n ϭ 32), Microsporum nanum (n ϭ 1), Microsporum praecox (n ϭ 1), Microsporum racemosum (n ϭ 1), Trichophyton ajelloi (n ϭ 2), Trichophyton balcaneum (n ϭ 2), Trichophyton concentricum (n ϭ 2), Trichophyton erinacei (n ϭ 7), Trichophyton interdigitale (n ϭ 21), Trichophyton mentagrophytes (n ϭ 122), Trichophyton phaseoliforme (n ϭ 1), Trichophyton rubrum (n ϭ 144), Trichophyton schoenleinii (n ϭ 2), Trichophyton simii (n ϭ 2), Trichophyton tonsurans (n ϭ 18), Trichophyton verrucosum (n ϭ 1), and Trichophyton violaceum (n ϭ 7). The majority of strains were clinical isolates from different hospitals in Spain and the United Kingdom, and numerous reference strains from the Centraalbureau voor Schimmelcultures were also tested. The fungi were mai...

This study prospectively evaluated the prevalence and risk factors of tinea unguium and tinea pedis in the general adult population in Madrid, Spain. One thousand subjects were clinically examined, and samples of nails and scales from the interdigital spaces of the feet were taken from those patients presenting with signs or symptoms of onychomycosis and/or tinea pedis, respectively. In addition, a sample from the fourth interdigital space of both feet was collected from all individuals with a piece of sterilized wool carpet. Tinea unguium was defined as a positive direct examination with potassium hydroxide and culture of the etiological agent from subjects with clinically abnormal nails. Patients with positive dermatophyte cultures of foot specimens were considered to have tinea pedis. The prevalence of tinea unguium was 2.8% (4.0% for men and 1.7% for women), and the prevalence of tinea pedis was 2.9% (4.2% for men and 1.7% for women). The etiological agents of tinea unguium were identified asTrichopyton rubrum (82.1%), followed by Trichopyton mentagrophytes var. interdigitale (14.3%) andTrichopyton tonsurans (3.5%). Trichophyton rubrum (44.8%) and Trichophyton mentagrophytes(44.8%), followed by Epidermophyton floccosum (7%) andT. tonsurans (3.4%), were the organisms isolated from patients with tinea pedis. The percentage of subjects who suffered simultaneously from both diseases was 1.1% (1.7% for men and 0.6% for women). In a multivariate logistic regression analysis, age (relative risk [RR], 1.03) and gender (RR, 2.50) were independent risk factors for tinea unguium, while only gender (RR, 2.65) was predictive for the occurrence of tinea pedis. In both analyses, the presence of one of the two conditions was associated with a higher risk for the appearance of the other disease (RR, >25).

Systemic yeast infections are a common consequence of immunosuppression, long-term indwelling catheters, and endocrinopathies. Subcutaneous, cutaneous, and superficial yeast infections also occur in both immunosuppressed and immunocompetent populations. Fluconazole is commonly used for serious mucocutaneous and systemic disease, as well as for postsurgical and posttransplant prophylaxis. Given the widespread use of this agent, concerns about the development of resistance in yeast have been raised (11,17,22).Recently, a new extended-spectrum triazole, voriconazole (Vfend; Pfizer), has been approved by the U.S. Food and Drug Administration (FDA) for first-line treatment of invasive aspergillosis and for treatment of patients refractory to other therapies for serious infections caused by Scedosporium apiospermum and Fusarium spp. In Europe, voriconazole has been approved for treatment of invasive aspergillosis, treatment of fluconazole-resistant serious invasive Candida (including Candida krusei) infections, and treatment of serious fungal infections by Scedosporium spp. and Fusarium spp. A major advantage of voriconazole over other recently approved antifungal agents used to treat systemic disease is that it can be administered orally after initial intravenous loading and administration of maintenance doses. While voriconazole does not yet have an FDA-approved indication for the treatment of Candida infections, phase III clinical trials are ongoing and voriconazole has shown enhanced activity against various yeast species in vitro (3,10,19 have not yet been established. Pharmacokinetically, fluconazole differs from voriconazole in that its concentration in serum is dependent on the dose administered; i.e., a higher dose of fluconazole leads to a higher concentration in serum (and hence the use of the S-DD designation) (6). The approved dosing regimen for voriconazole is two loading doses of 6 mg/kg given intravenously 12 h apart, followed by 4 mg/kg (or 3 mg/kg if tolerance is a problem) every 12 h as a maintenance

Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging. Circulating biomarkers for the diagnosis of FP have limitations and the combination of different assays in serum samples and directly from the target organ may further improve the diagnosis of FP. We prospectively assessed the diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid (BAL) and serum GM and (1→3)-β-D-glucan (BG) assays in critically ill patients at risk of FP. Patients with FP were classified according to European Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria, with modifications. Out of 847 admissions, 51 patients were eligible. There were nine invasive aspergillosis (IA) cases (four proven, five probable), three proven Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA and proven PJP). The diagnostic accuracy as given by the area under the receiver operating characteristic curve in IA cases (proven and probable) for GM in BAL was 0.98 (95% CI, 0.94-1.00), whilst for GM and BG in serum it was 0.85 (95% CI, 0.74-0.96) and 0.815 (95% CI, 0.66-0.96), respectively. For IA cases (proven and probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p 0.025 and p 0.032, respectively). In one of four proven and one of six probable IA cases, GM in serum remained negative, whereas GM in BAL was positive. In patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1-10 days) before Aspergillus was cultured. GM detection in BAL appears to improve the diagnosis of IA in critical patients.

A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.

Itraconazole is the first azole derivate that matches griseofulvin for the treatment of tinea capitis in children. The drug also appears to be better tolerated than griseofulvin.

The in vitro activity of the new triazole albaconazole (UR-9825) in comparison with those of flucytosine, fluconazole, ketoconazole, itraconazole, and voriconazole against 70 strains of Malassezia spp. was determined by a microdilution method using a colorimetric indicator for metabolic activity. Albaconazole showed an in vitro profile similar to those of the different antifungals tested (MIC < 0.06 g/ml for all the strains).Yeasts of the genus Malassezia are part of the normal mycota of the skin of humans and other warm-blooded animals, particularly in areas rich in sebaceous glands (19). Malassezia species may also be etiological agents of skin disorders and, uncommonly, systemic infections (3, 6, 16, 24, 30).In 1997, the National Committee for Clinical Laboratory Standards approved a broth micro-and macrodilution method for susceptibility testing of yeasts with RPMI 1640 medium (NCCLS-M27A) (21). However, this document is not applicable to Malassezia species other than Malassezia pachydermatis, because these organisms do not grow without lipidic substances in the medium. Only a few systems for in vitro susceptibility testing of Malassezia species have been described. In addition to present measurements in solid media, several microdilution methods have been used, but the different liquid media used, such as modified Dixon (19,27) and LeemingNotman (15), are turbid; consequently, the visual and turbidimetric results are difficult to interpret. A liquid medium method has been observed to overcome the difficulties in growth reading if one uses a colorimetric indicator for metabolic activity (Alamar blue) (25). Recently, Nakamura et al. (20) described a new microdilution method based on the urease activity of Malassezia spp.Albaconazole (ABC) is a new systemic triazole under development by J. Uriach & Cia S.A. (Barcelona, Spain) with both potent and broad-spectrum antifungal activity, good pharmacokinetics, and excellent bioavailability. It has demonstrated good in vitro activities against pathogenic yeasts (23), dermatophytes (10), and some filamentous fungi (4), including Scedosporium prolificans (5). It has also been shown to be active in the treatment of systemic aspergillosis and candidiasis in experimental animal models (2).The aim of this study was to compare the in vitro activity of ABC with those of five antifungal drugs, namely, flucytosine (5FC), fluconazole (FLC), ketoconazole (KTC), itraconazole (ITC), and voriconazole (VRC), against 70 isolates of Malassezia, namely, M. furfur (n ϭ 24), M. pachydermatis (n ϭ 10), M. sympodialis (n ϭ 21), and M. slooffiae (n ϭ 15). M. furfur was obtained from human skin, that of neonates with long stays in intensive care units. M. pachydermatis and M. slooffiae were obtained from healthy and diseased ears of dogs and pigs, respectively. M. sympodialis was isolated from normal human skin. Susceptibility testing of the drugs was initially performed with M. restricta (n ϭ 1), M. obtusa (n ϭ 1), and M. globosa (n ϭ 24). However, we were unable to obtain MICs due to the ...