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. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents.

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. In this paper, the authors review the prevalence of non-albicans candida over the past 5 years, and assess the efficacy of amphotericin and flucytosine vaginal cream in the treatment of non-albicans VVC. METHODS: Retrospective review of all vaginal yeast isolates collected from women attending a city centre sexual-health clinic between 2004 and 2008. The women prescribed amphotericin and flucytosine vaginal cream were identified through pharmacy records, and their clinical notes reviewed for treatment outcome. RESULTS: Between 2004 and 2008, the number of isolates of all Candida species increased with increasing clinic workload, but the prevalence of non-albicans yeasts remained stable at between 0.87 and 1.06%. Eighteen patients were prescribed amphotericin and flucytosine vaginal cream. At follow-up, all 18 were clear of their initial yeast isolate on culture, but two had persistent symptoms and had positive cultures for C albicans. CONCLUSIONS: There is no evidence of any increase in prevalence of non-albicans Candida species such as C glabrata. The authors have treated 18 women who had non-albicans VVC with amphotericin and flucytosine vaginal cream and achieved clearance of the non-albicans species in all of them.

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. PARTICIPANTS: All neonates (< or = 28 days of age) or infants (> 28 days of age) admitted to the unit during the 20-week period from October 1995 to March 1996. METHODS: All infants or neonates were swabbed on the day of admission and every third day thereafter and risk factors were collected for every day on the unit. RESULTS: During the study period, 245 neonates and 42 infants were sampled for their entire duration of stay on the unit. Of these, 41 infants (97.6%) were colonized with Malassezia on admission to the unit and thereafter, as assessed by subsequent samples. Within the neonate population, 78 (31.8%) became colonized, but none were colonized immediately after birth. Univariate analysis showed that many factors appeared to be significantly associated with colonization in the neonates, including use of ventilation, presence of central venous catheters, use of parenteral nutrition, and use of antibacterial or antifungal drugs. However, when the data were analyzed by multivariate logistic regression to control for confounding variables, only gestational age and length of stay on the unit were found to be significantly associated with colonization. CONCLUSION: Colonization of infants is not as unusual as previously thought and many infants have established a cutaneous Malassezia commensal flora by the age of 3 to 6 months. Factors that predispose to colonization in neonates may not be the same as those that predispose to infection.

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. The finding that the genus Malassezia is immunomodulatory is important in understanding its ability to cause disease. Stimulation of the reticuloendothelial system and activation of the complement cascade contrasts with its ability to suppress cytokine release and downregulate phagocytic uptake and killing. The lipid-rich layer around the yeast appears to be pivotal in this alteration of phenotype. Defining the nonspecific immune response to Malassezia species and the way in which the organisms modulate it may well be the key to understanding how Malassezia species can exist as both commensals and pathogens.