Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021.

Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure-response relationship with either a narrow therapeutic window, large dose-exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non-compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM-guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided

Evaluation of a Pilot Vancomycin Precision Dosing Advisory Service on Target Exposure Attainment Using an Interrupted Time Series Analysis

This study evaluated the ability of a pilot therapeutic drug monitoring (TDM) Advisory Service to facilitate vancomycin therapeutic target attainment within a real-world clinical setting. The Service provided area under the concentration-time curve (AUC)–guided vancomycin dose recommendations, using Bayesian forecasting software and clinical expertise, to prescribers at an Australian hospital. A retrospective audit of intravenous vancomycin therapy (> 48 hours) in adults (≥ 18 years old) was undertaken over a 54-month period to evaluate attainment of established vancomycin pharmacokinetic/pharmacodynamic targets (AUC over 24 hours / minimum inhibitory concentration: 400–600) before (36-month period) and after (18-month period) Service implementation. Interrupted time series analysis was employed to evaluate monthly measures of the median proportion of therapy spent within the target range. Indices of time to target attainment were also assessed before and after Service implementation. The final cohort comprised 1,142 courses of vancomycin (816 patients); 835 courses (596 patients) and 307 courses (220 patients) administered before and after Service implementation, respectively. Prior to piloting the Service, the median proportion of time in the target range was 40.1% (95% CI, 34.3–46.0%); this increased by 10.4% (95% CI, 1.2–19.6%, P = 0.03) after the Service, and was sustained throughout the post-Service evaluation period. Post-Service target attainment at 48–72 hours after initiation of therapy was increased (7.8%, 95% CI, 1.3–14.3%, P = 0.02). The findings of this study provide evidence that a consultative TDM Service can facilitate attainment of vancomycin therapeutic targets; however, optimization of the Service may further improve the use of vancomycin

Aspectos epidemiológicos de pacientes com lesões ungueais e cutâneas causadas por Scytalidium spp Epidemiological aspects of patients with ungual and cutaneous lesions caused by Scytalidium spp

FUNDAMENTO: As dermatomicoses causadas por fungos filamentosos não dermatófitos são infecções raras, exceto as onicomicoses, cuja prevalência vem crescendo nos últimos anos. Dentre esses agentes etiológicos destacam-se o Scytalidium dimidiatum e o S. hyalinum, fungos emergentes responsáveis por micoses em unhas e pele. OBJETIVO: Investigar as características epidemiológicas das onicomicoses e micoses de outras localizações causadas pelos fungos do gênero Scytalidium, utilizando-se como parâmetros sexo, idade e localizações das lesões. MÉTODOS: Avaliaram-se 81 amostras com cultura positiva para o gênero em estudo, oriundas de 74 pacientes encaminhados ao Laboratório de Investigação em Dermatologia (ID) situado na cidade do Rio de Janeiro (RJ), no período de 1997 a 2006. As amostras foram submetidas a confirmação diagnóstica por exame direto e cultura. RESULTADOS: A prevalência de onicomicoses por Scytalidium spp. foi de 0,87%, entre as idades de 41 e 60 anos (48,64%). Em relação à localização das lesões, os pés foram mais acometidos (91,36%), com predomínio do hálux esquerdo. No exame direto, as estruturas mais encontradas foram hifas hialinas; na cultura, a espécie S. dimidiatum foi a mais frequente. CONCLUSÃO: As onicomicoses por Scytalidium spp. são raras e o S. dimidiatum foi a espécie mais isolada neste laboratório no período em estudo.<br>BACKGROUND: Dermatomycoses caused by non-dermatophyte filamentous fungi are rare infections, except for onychomycosis, whose prevalence has increased over the past few years. Among these etiologic agents, we highlight Scytalidium dimidiatum and S. hyalinum, emergent fungi that cause mycoses that affect the nails and skin. OBJECTIVE: To investigate the characteristics of onychomycosis and other mycoses caused by the fungi Scytalidium spp, using sex, age and site of infection as parameters. METHODS: Eighty-one samples were evaluated showing positive culture for Scytalidium spp, obtained from 74 patients referred to the Laboratory of Investigation in Dermatology (ID) located in the city of Rio de Janeiro, RJ, between 1997 and 2006. The samples were submitted to diagnostic confirmation through direct exam and culture. RESULTS: The prevalence of onychomycosis caused by Scytalidium spp. was of 0,87%. The most prevalent age was between 41-60 years (48.64%). Regarding the site of infection, the feet (91.36%) were most affected, with predominance of the left hallux. Hyaline hyphae were the most common structures in direct examination and the species S. dimidiatum was the most frequent in culture. CONCLUSION: Onychomycosis caused by Scytalidium spp. is rare and S. dimidiatum was the most isolated species in this laboratory during the period of the study