407. Prospective, Observational Study of Voriconazole Therapeutic Drug Monitoring (VOR TDM) in Lung Transplant (LT) Recipients
Session: Poster Session: Hospital-acquired and Transplant Infections
Friday, October 30, 2009: 12:00 AM
Room: Poster Hall A
Background: Vor TDM has been advocated in patients (pts) treated for fungal infections. Although controversial, trough levels of 1-2 µg/ml have been proposed as therapeutic. Data are less clear for pts receiving Vor prophylaxis (px) post LT. We conducted a prospective, observational study of TDM in LT pts on Vor px
Methods: LT pts from Jan-May 2009 were followed with weekly trough Vor TDM. All pts received 2 doses IV load (6 mg/kg) then 200 mg po BID. TDM was performed by HPLC, beginning after ≥ 7 d of px. Level <0.2 µg/mL was undetectable.
Results: 31 LT pts (30 white, 20 men) underwent TDM, 28 of whom were serially tested. 42% had COPD, 36% IPF, and 10% CF. On first Vor measurement, 49% were ≤ 1 µg/mL (3 undetectable, 6 between 0.2-0.5, 6 between 0.5-1.0), 19% 1-2, 19% 2-4, and 13% > 4. Upon serial testing, 50% had significant (>0.5) variation in levels, 64% of whom were ≥ 65 yrs. 39% had persistent levels ≤ 1, including 18% with persistent levels ≤ 0.5. CF and age ≥ 65 yrs were associated with increased risk of undetectable levels and levels > 4, respectively (p=0.04 and 0.03). Vor toxicity (rising LFTs and GI intolerance) occurred in 13%, but levels were > 3 in only half; all pts with toxicity were switched to inhaled AmB. Despite Vor px, 29% had fungi isolated at bronchoscopy, including 16% with proven invasive fungal disease (anastomotic fungal infection=4; thrush=1). 60% of fungal diseases and 50% of anastomotic infections occurred despite levels > 1. Vor was not discontinued by physicians on the basis of levels in the absence of toxicity or fungal infection.
Conclusion: Subtherapeutic Vor levels are common in LT pts receiving px, and subtherapeutic initial levels generally remain persistent. Pts ≥ 65 are at risk for high levels and variations in levels. Pts with CF are at risk for undetected levels. PK/PD in elderly and CF populations merit further study. Anastomotic fungal infections occur in 13% of patients, even in those with therapeutic serum levels, suggesting that Vor does not reliably achieve adequate levels at these mucosal sites. In such cases, inhaled AmB might be a preferable option.
Cornelius Clancy, MD, Dimitra Mitsani, MD2, M. Hong Nguyen, MD2, Yoshiya Toyoda, MD, PhD2 and  D. Mitsani, None..
M. Nguyen, None..
Y. Toyoda, None..
C. J. Clancy, None., (1)UPMC, Pittsburgh, PA