Voriconazole therapeutic drug monitoring among lung transplant recipients receiving targeted therapy for invasive aspergillosis.
fungal infection
invasive aspergillosis
lung transplant
therapeutic drug monitoring
voriconazole
Journal
Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
09
04
2022
received:
01
03
2022
accepted:
10
05
2022
pubmed:
17
5
2022
medline:
11
8
2022
entrez:
16
5
2022
Statut:
ppublish
Résumé
Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs. Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome. One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 μg/ml (range 0.06-7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 μg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 μg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 μg/ml (OR 3.11; 95% CI: 0.53-20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 μg/ml was predictive of hepatotoxicity. Our data suggests that a voriconazole TDM range between 0.72 μg/ml and 2.13 μg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.
Sections du résumé
BACKGROUND
Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs.
METHODS
Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome.
RESULTS
One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 μg/ml (range 0.06-7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 μg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 μg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 μg/ml (OR 3.11; 95% CI: 0.53-20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 μg/ml was predictive of hepatotoxicity.
CONCLUSIONS
Our data suggests that a voriconazole TDM range between 0.72 μg/ml and 2.13 μg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.
Substances chimiques
Antifungal Agents
0
Voriconazole
JFU09I87TR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14709Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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