%0 Journal Article %1 Mitsani2012 %A Mitsani, Dimitra %A Nguyen, M Hong %A Shields, Ryan K. %A Toyoda, Yoshiya %A Kwak, Eun J. %A Silveira, Fernanda P. %A Pilewski, Joseph M. %A Crespo, Maria M. %A Bermudez, Christian %A Bhama, Jay K. %A Clancy, Cornelius J. %D 2012 %J Antimicrob Agents Chemother %K transplantation prophylaxis fungal toxicity %N 5 %P 2371--2377 %R 10.1128/AAC.05219-11 %T 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. %U http://dx.doi.org/10.1128/AAC.05219-11 %V 56 %X 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.

@article{Mitsani2012, 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.}, added-at = {2012-07-11T00:27:19.000+0200}, author = {Mitsani, Dimitra and Nguyen, M Hong and Shields, Ryan K. and Toyoda, Yoshiya and Kwak, Eun J. and Silveira, Fernanda P. and Pilewski, Joseph M. and Crespo, Maria M. and Bermudez, Christian and Bhama, Jay K. and Clancy, Cornelius J.}, biburl = {https://www.bibsonomy.org/bibtex/25e69103701b04a3329c48daf508bd3d5/aorchid}, description = {see page 61 in notebook 00002 for details.}, doi = {10.1128/AAC.05219-11}, file = {:ID_General/TransplantClinical/AntimicrobAgentsChemother.56.2371.pdf:PDF}, groups = {public}, institution = {Divisions of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.}, interhash = {83f1f90f07782b55dfacfffab031d34b}, intrahash = {5e69103701b04a3329c48daf508bd3d5}, journal = {Antimicrob Agents Chemother}, keywords = {transplantation prophylaxis fungal toxicity}, language = {eng}, medline-pst = {ppublish}, month = May, number = 5, pages = {2371--2377}, pii = {AAC.05219-11}, pmid = {22330924}, timestamp = {2012-07-11T00:27:19.000+0200}, title = {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.}, url = {http://dx.doi.org/10.1128/AAC.05219-11}, username = {aorchid}, volume = 56, year = 2012 }