885. Voriconazole Therapeutic Drug Level Monitoring and Relation to Clinical Outcomes: Results from a Cohort Study
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
  • Voriconazole_IDSA_09302011_FINAL.pdf (1.5 MB)
  • Background: Invasive fungal infections (IFI) are associated with high morbidity and mortality. Voriconazole is approved for treatment of invasive aspergillosis and other IFIs. Voriconazole therapeutic drug monitoring  (TDM) is recommended, but it remains unclear whether TDM improves clinical outcomes. 

    Methods:  We performed a cohort study of patients at the University of Washington Medical Center and Fred Hutchinson Cancer Research Center from 2007-2009 through electronic medical chart review. Data were analyzed using STATA 11. Univariable Cox proportional hazard regression models were used to examine the effect of therapeutic levels on outcomes, and logistic regression was used to evaluate adverse events.

    Results: 108 patients had voriconazole TDM performed. 84 (77.8%) had a hematologic malignancy, of whom 47 (55.9%) had undergone hematopoietic cell transplantation. The primary reasons for treatment were pulmonary aspergillosis (83, 76.8%), other invasive mould infections (13, 12.0%) and candidiasis (9, 8.3%). There was a high degree of variability in voriconazole drug levels between patients, with a range of <0.10 to 20 ug/ml. 46 (43.4%) had proven or probable invasive fungal disease. Of these, 25 (54.3%) achieved partial or complete response to therapy. There was no significant relationship between drug levels and achievement of complete or partial response at 6 weeks (HR 0.48, 95% CI 0.15-1.54, p-value 0.22) or 12 weeks (HR 0.70, 95% CI 0.30-1.64, p-value 0.41). Among those with pulmonary aspergillosis, radiologic response was noted in 37/67 (55.2%). There was no significant relationship between therapeutic drug levels and radiologic response (OR 0.71, 95% CI: 0.30-1.71, p-value 0.45). 45 (41.7%) patients experienced adverse events, with 19 cases of encephalopathy and 15 cases of hepatotoxicity. Voriconazole levels > 5 ug/ml were not associated with increased incidence of encephalopathy (OR 1.00, 95% CI: 0.26-3.93, p-value 1.00) or hepatotoxicity (OR 3.38, 95% CI: 0.98-11.6, p-value 0.05), though there was a trend towards significance. 

    Conclusion: In contrast to previous studies, these results do not show that therapeutic drug levels of voriconazole are associated with better clinical outcomes or reduced toxicity.

    Subject Category: M. Mycology including clinical and basic studies of fungal infections

    Helen Chu, MD1, Rupali Jain, PharmD1, Hu Xie, MSc2, Paul Pottinger, MD1 and David Fredricks, MD2, (1)University of Washington Medical Center, Seattle, WA, (2)Fred Hutchinson Cancer Research Center, Seattle, WA


    H. Chu, None

    R. Jain, None

    H. Xie, None

    P. Pottinger, None

    D. Fredricks, Pfizer: Investigator, Participated in clinical trial with support to institution

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