Therapeutic Drug Monitoring of Antifungal Drugs: Another Tool to Improve Patient Outcome?

Abstract

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.

Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure

“…Collectively, these data indicate the predictive potential of FLZ MIC ≥ 32 µg/mL for FLZ TF and of FKS sequencing combined with AFST data for echinocandin TF. However, it should be noted that TF cannot be exclusively attributed to microbiological characteristics of the isolates; other factors may be involved, including serum concentration of the antifungal which shows patient‐to‐patient variations, highlighting the importance of therapeutic drug monitoring to attain a favourable clinical outcome 58 . Moreover, considering that all patients with azole/echinocandin‐resistant C glabrata isolates had a catheter inserted (except one patient infected with isolate #G6 without clinical data), it is plausible that catheter removal may have implications on clinical outcome.…”

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients

“…When used in critically ill patients, voriconazole demonstrated a large inter-patient variability in voriconazole plasma concentrations ranging from ≤ 1 mg/L for 37% of patients to > 5.5 mg/L for 19% of them [ 4 ]. Moreover, sub-therapeutic triazoles concentrations including voriconazole were linked to poor outcome compared with optimal concentrations [ 5 , 6 ], whereas voriconazole supra-therapeutic concentrations were identified as a significant independent risk factor for hepatotoxicity in critically ill patients [ 7 , 8 ]. Thus, voriconazole TDM is needed in critically ill patients to improve efficacy and safety as recently demonstrated [ 9 ].…”

Emerging Invasive Fungal Infections in Critically Ill Patients: Incidence, Outcomes and Prognosis Factors, a Case-Control Study

“…Future development axes to improve the prognosis would involve new laboratory diagnostic and imaging procedures and the search for new antifungal compounds. In any case, drug monitoring should be a preliminary to any antifungal treatment because a large proportion of patients exhibit low drug concentrations leading to poor outcomes, especially in ICU settings [ 37 ].…”