Yazarlar : Mitsani D, Nguyen MH, Shields RK, et al

Yayın : Antimicrob Agents Chemother.

Yayın Yılı : 2012

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22330924

Konu : Enfeksiyon

Literatür İçeriği :  

Abstract

Background. Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown.Methods. Prospective, observational study of lung transplant recipients (n=93) receiving voriconazole prophylaxis. Serum troughs (n=331) were measured by high-pressure liquid chromatography.Results. Median initial and subsequent troughs were 1.91 and 1.46 μg/mL, respectively. Age directly correlated with initial troughs (p=0.005). Patients ≥60 years 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 patients developed invasive fungal infection (tracheobronchitis) or fungal colonization, respectively. Median troughs at 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 ≤1.5 μg/mL (p=0.01), and among patients with no trough >1.5 μg/mL (p=0.007). Other cut-off troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (p=0.003), but not other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93). Troughs did not differ at times of suspected drug-induced hepatotoxicity, CNS toxicity or nausea/vomiting, and in absence of toxicity.Conclusions. Voriconazole prophylaxis was most effective at troughs >1.5 μg/mL. A cut-off for toxicity was not identified, but troughs >4 μg/mL were rare. The data support a target range of >1.5-4 μg/mL.

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