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Introduction: This study aimed to examine the relationship among adequate dose, serum concentration and clinical outcome in a non-selected group of hospitalized patients receiving antifungals. Methods: Prospective cross-sectional study performed between March 2015 and June 2015. Dosage of antifungals was considered adequate according to the IDSA guidelines, whereas trough serum concentrations (determined with HPLC) were considered adequate as follows: fluconazole [ 11 lg/ml, echinocandins [ 1 lg/ ml, voriconazole 1-5.5 lg/ml and posaconazole [ 0.7 lg/ml. Results: During the study period, 84 patients (65.4% male, 59.6 years) received antifungals for prophylaxis (40.4%), targeted (31.0%) and empirical therapy (28.6%). The most frequent drug was micafungin (28/84; 33.3%) followed by fluconazole (23/84; 27.4%), voriconazole (15/84; 17.9%), anidulafungin (8/84; 9.5%), posaconazole (7/84; 8.3%) and caspofungin (3/ 84; 3.6%). Considerable interindividual variability was observed for all antifungals with a large proportion of the patients (64.3%) not attaining adequate trough serum concentrations, despite receiving an adequate antifungal dose. Attaining the on-target serum antifungal level was significantly associated with a favorable clinical outcome (OR = 0.02; 95% CI 0.01-0.64; p = 0.03), whereas the administration of an adequate antifungal dosage was not. Conclusions: With the standard antifungal dosage, a considerable proportion of patients have low drug concentrations, which are associated with poor clinical outcome.

A previous audit to assess the quality of antifungal use was performed in our hospital in 2011. After 5 years of antifungal stewardship program (AFS), we performed a follow-up audit in order to describe the long-term effect of such program. Using a predefined score, we evaluated the antifungal use in 100 consecutive adult inpatients receiving systemic antifungals. Results of the present audit were compared with those of a previous one, performed in 2011, before the implementation of our AFS. After 5 years, AFS program has induced a change in the population who received antifungal drugs in our hospital with a reduction in medical patients and a relative higher prescription among hematological ones. As for indications, empirical use decreased very significantly (from 62 to 30%, p < 0.001), while tailored treatment (from 20 to 41%, p = 0.001) and prophylaxis (from 15 to 27%, p = 0.03) increased. Compared to 2011, we also observed an improvement in the optimal choice of antifungal drug, route of administration, and microbiological adjustment. However, no significant improvement was observed regarding adequacy of length of therapy or optimal dosage or administration route. Although we observed an increase in the number of optimal DOTs used, the potential estimated savings continued to be high (~ €44,199 for every 100 patients receiving antifungals). Our study is the first to show the impact on the use of antifungal drugs exerted by a prolonged non-coercive AFS program. We also demonstrate the utility of a periodic audit of antifungal use in order to point out new goals for future interventions.

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