Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology.

The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics-pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance.

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics.

Treatment or prophylaxis of invasive fungal infection in recipients of haemopoietic SCT (HSCT) may require management of coexistent malnutrition, organ dysfunction and GVHD, all of which create added potential for inter- and intra-patient variations in drug metabolism as well as drug interactions. Polymorphism is common in genes encoding pathway components of antifungal drug metabolism such as enzymes (cytochrome P450 (CYP450), glutathione S-transferase, N-acetyltransferase and uridine 5'-diphospho-glucuronosyltransferase), uptake transporters (organic cationic transporter, novel organic cationic transporter, organic anion transporter protein (OATP), organic anion transport (OAT), and peptide tranporter) and efflux transporters (breast cancer resistance protein, bile sale export pump (BSEP), multidrug and toxin extrusion type transporter, multidrug resistance protein (MRP), OAT, permeability glycoprotein (P-gp), and urate transporter). Specific polymorphisms may be generalised throughout a population or largely confined to ethnic groups.

Prevalence and management of non-albicans vaginal candidiasis.

Objectives: It is thought that widespread use of 'over-the-counter' azoles may increase the incidence of resistant Candida species such as Candida glabrata. Infections with species other than Candida albicans frequently do not respond to standard azole treatments. Intravaginal nystatin is an option but is no longer available in the UK.

Histoplasmosis in Europe: report on an epidemiological survey from the European Confederation of Medical Mycology Working Group.

The purpose of this survey was to systematically collect data on individuals with histoplasmosis in Europe over a 5-year period (from January 1995 to December 1999). This included information on where and how the infection was acquired, the patient's risk factors, the causative organism, how the infection was diagnosed and what therapy the patients received. Data were sent on a standardized survey form via a national convenor to the coordinator.

Update on the genus Malassezia.

Malassezia yeasts are commensals of normal human skin, but also cause pityriasis versicolor, seborrhoeic dermatitis and evidence is accumulating that they play a significant role in atopic eczema/dermatitis syndrome (AEDS; formerly atopic dermatitis). The taxonomy of the genus has changed considerably and is likely to change more in the future. Our understanding of the interaction between Malassezia and the host demonstrates that it has the paradoxical ability to both stimulate and suppress the immune response directed against it and there is a fine balance in its existence at the interface between commensalism and pathogenicity.

Recent developments in the immunology and biology of Malassezia species.

Malassezia spp. are members of the normal cutaneous flora, but are also associated with several cutaneous diseases. Recent studies of the interaction of Malassezia spp.

Testing of antifungal combinations against yeasts and dermatophytes.

Background: Fungal infections of the nail are a common and chronic problem. The main pathogens responsible for onychomycosis are dermatophytes, yeasts and moulds. Despite significant improvements, approximately 20% of patients with onychomycosis still fail on antifungal therapy.

Skin colonization by Malassezia in neonates and infants.

Objective: To identify the timing, pattern, and determinants of colonization of neonates by Malassezia.

Design: Prospective observational study.

Setting: A neonatal medical and surgical unit consisting of 10 special care, 10 high-dependency, 10 intensive care, and 10 surgical cots.

Production of the mycelial phase of Malassezia in vitro.

To study the pathogenicity of Malassezia, the agent of pityriasis versicolor, it is necessary to obtain the mycelial form in vitro. A range of different components and conditions were tested to induce yeast cells of the organism to produce mycelia in vitro using different culture media. A mycelial culture medium was developed that consisted of bacteriological peptone, glucose, yeast extract, ox bile, glycerol, glycerol monostearate, Tween 80, squalene, glycine, potassium nitrate, sodium chloride, ferrous sulphate and magnesium sulphate with or without agar.

Immunology of diseases associated with Malassezia species.

Malassezia species are members of the human cutaneous commensal flora, in addition to causing a wide range of cutaneous and systemic diseases in suitably predisposed individuals. Studies examining cellular and humoral immune responses specific to Malassezia species in patients with Malassezia-associated diseases and healthy controls have generally been unable to define significant differences in their immune response. The use of varied antigenic preparations and strains from different Malassezia classifications may partly be responsible for this, although these problems can now be overcome by using techniques based on recent work defining some important antigens and also a new taxonomy for the genus.

A two year global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion.

The in-vitro activity of fluconazole against 46,831 yeast isolates collected over a two-year period from 57 laboratories in 33 countries worldwide was assessed using a disc diffusion method. Candida albicans was the organism isolated most frequently, accounting for 68.6% of the total number of isolates.

An investigation into the pathogenesis of vulvo-vaginal candidosis.

Objective: To monitor yeasts isolated from women during and between episodes of recurrent vulvo-vaginal candidosis (VVC) to determine whether vaginal relapse or re-infection occurred.

Methods: Women presenting at the genitourinary medicine clinic with signs and symptoms of VVC were recruited to the study (n = 121). A vaginal washing, high vaginal swab (HVS) and rectal swab were taken and the women treated with a single 500 mg clotrimazole pessary.

Vaginal yeasts in the era of "over the counter" antifungals.

Objective: To establish whether there has been any rise in the prevalence of non-albicans Candida species isolated from vaginal swabs since the introduction of "over the counter" antifungal treatments.

Method: A retrospective review looking at all positive vaginal yeast isolates collected from women attending one genitourinary medicine clinic during the 6 year period from 1993 to 1998 inclusive. All positive vaginal yeast isolates were included, regardless of whether or not the patients were symptomatic.

Cell-mediated immunity to the mycelial phase of Malassezia spp. in patients with pityriasis versicolor and controls.

Background: Malassezia is the aetiological agent of pityriasis versicolor. The mycelial phase of the organism predominates in lesions of pityriasis versicolor.

Objectives: To evaluate the cell-mediated immune (CMI) response to the mycelial phase of Malassezia in patients with this disease, which has not previously been studied.

The role of Malassezia species in the ecology of human skin and as pathogens.

The new taxonomic structure of the lipophilic genus Malassezia was presented with key characteristics for the seven described species. Among techniques used for epidemiological surveys, the pulsed field gel electrophoresis (PFGE) was found to be of little value in contrast to randomly amplified polymorphic DNA (RAPD). Immunological studies still yielded conflicting results but at least the immunomodulatory capacity of Malassezia yeasts appeared to be related to the cell wall lipids.

IgG subclasses specific to Staphylococcus epidermidis and Propionibacterium acnes in patients with acne vulgaris.

IgG subclasses specific to Staphylococcus epidermidis and Propionibacterium acnes were determined in sera from patients with mild, moderate or severe acne and from a control group. Titres specific to S. epidermidis were all within the same range and did not differ between groups.

Humoral immunity to Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrheic dermatitis and controls.

This study examined the humoral immune responses to Malassezia furfur serovars A, B and C of 10 patients with pityriasis versicolor, 10 patients with seborrheic dermatitis and 20 age- and sex-matched controls. A transferable solid-phase ELISA was used to determine titres of total Igs, IgM, IgA and IgG specific to M. furfur serovars A, B and C.

Cell-mediated immune responses to Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrheic dermatitis and controls.

It has been postulated that patients with Malassezia furfur-associated dermatoses have a deficient cell-mediated immune response to M. furfur. This study examined the cell-mediated immune responses to M.

The carriage of Malassezia furfur serovars A, B and C in patients with pityriasis versicolor, seborrhoeic dermatitis and controls.

The aetiological role of Malassezia furfur in various dermatoses is controversial. The role of the three serovars of M. furfur in Malassezia-associated diseases has not been investigated.