Prospective, Observational Study of Voriconazole Therapeutic Drug Monitoring among Lung Transplant Recipients Receiving Prophylaxis: Factors Impacting Levels of and Associations between Serum Troughs, Efficacy, and Toxicity
Open Access
- 1 May 2012
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (5), 2371-2377
- https://doi.org/10.1128/aac.05219-11
Abstract
Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients ( n = 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs ( n = 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs ( P = 0.005). Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml ( P = 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml ( P = 0.01) and among patients with no trough of >1.5 μg/ml ( P = 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels ( P = 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.Keywords
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