Antifungal Prophylaxis in Lung Transplantation—A World-wide Survey

Neoh, Chin Fen; Snell, Gregory I; Kotsimbos, T.; Levvey, Bronwyn; Morrissey, C. Orla; Slavin, Monica A; Stewart, Kay; Kong, David Chee Ming

doi:10.1111/j.1600-6143.2010.03375.x

Cited by 136 publications

(162 citation statements)

References 20 publications

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“…Voriconazole, a broad-spectrum azole with activity against yeasts and molds, is considered the treatment of choice for IA (2). Given its excellent activity against Aspergillus and high bioavailability, voriconazole has also become the preferred agent for antifungal prophylaxis in many lung transplant centers (3,4).…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Voriconazole Hepatotoxicity at 12 Weeks in Lung Transplant Recipients

Singer

et al. 2012

American Journal of Transplantation

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Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazoleassociated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53-12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K-nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.

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Section: Introductionmentioning

confidence: 99%

Risk Factors for Voriconazole Hepatotoxicity at 12 Weeks in Lung Transplant Recipients

Singer

et al. 2012

American Journal of Transplantation

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“…The two most common IFIs among lung transplant recipients are pneumonia, which is caused most frequently by Aspergillus fumigatus and other molds, and anastomic site tracheobronchitis, which is caused by molds or yeasts. Fifty-nine percent of lung transplant programs worldwide employ universal antifungal prophylaxis (22,25). Voriconazole is effective in preventing IFIs among lung transplant recipients (17), and it has emerged as the preferred prophylactic agent (25).…”

mentioning

confidence: 99%

“…Fifty-nine percent of lung transplant programs worldwide employ universal antifungal prophylaxis (22,25). Voriconazole is effective in preventing IFIs among lung transplant recipients (17), and it has emerged as the preferred prophylactic agent (25). Drug intolerance is the main indication for switching from voriconazole to alternative regimens (25).…”

mentioning

confidence: 99%

“…The mean bioavailability of voriconazole among lung transplant recipients ranges from 24% to 64% compared to 96% in populations of individuals who did not receive a lung transplant (15). Nevertheless, only 26% of lung transplantation programs employ TDM (25). In late 2008, we instituted routine TDM of voriconazole troughs to ensure that our lung transplant recipients absorbed the drug and to help minimize toxicity.…”

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confidence: 99%

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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

Mitsani

Nguyen

Shields

et al. 2012

Antimicrob Agents Chemother

117

125

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ABSTRACTVoriconazole 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.

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“…The current prophylactic and treatment antifungal drug of choice for Aspergillus is voriconazole which has proven efficacy but significant bioavailability, drug-drug interaction and toxicity issues making therapeutic drug monitoring very important and useful [266][267][268][269][270][271][272][273]. A prophylaxis strategy is recommended when there is a high pre-test probability of Aspergillus being present and potentially causing serious complications as in LTR with Aspergillus in the sputum just prior to transplant surgery.…”

Section: Fungal Infectionsmentioning

confidence: 99%