809. Is There a Role for Therapeutic Dose Monitoring of Voriconazole Prophylaxis in Allogeneic Stem Cell Transplant Recipients?
Session: Poster Abstract Session: Antimicrobial Agents: PK/PD Studies
Friday, October 9, 2015
Room: Poster Hall
Background: Fungal infections are a leading cause of morbidity and mortality in recipients of allogeneic stem cell transplants, particularly in those with prolonged periods of neutropenia and/or significant graft versus host disease. Voriconazole is frequently used for fungal prophylaxis during high-risk periods in this population given its broad spectrum of coverage against yeasts, Aspergillus sp.,and other filamentous fungi. Voriconazole has nonlinear pharmacokinetics and oral bioavailability of 96% based on early studies in healthy individuals. Therapeutic dose monitoring of voricoanzole has been recommended in the treatment setting, but there is limited data to support this practice in prophylaxis dosing.

Methods: We conducted a retrospective chart review of 339 recipients of allogeneic and cord blood stem cell transplant between Jan 2008-Dec 2013, who received voriconazole as primary anti-fungal prophylaxis. Data collected included the frequency of voriconazole level monitoring (performed at the discretion of the physicians and pharmacists), the prevalence of subtherapeutic trough levels (<1.0 mcg/mL) and associated factors,  toxicities attributed to voriconazole, as well as number and characteristics of breakthrough fungal infections.

Results: 149 patients had at one voriconazole trough level performed. Initial trough levels ranged from undetectable to 8.8 mcg/mL with a median of 1.6 and a mean of 1.9. 40% of initial levels were <1.0. 50% of patients with subtherapeutic levels had doses increased with a repeat level performed, but the median and mean trough levels were unchanged

Therapeutic N=90

Non-Therapeutic N=59

P-value

Male

57 (66%)

29 (49%)

0.09

Age (median)

56

51

0.11

Weight (median)

83.9

79.4

0.24

AML

34 (37.8%)

19 (32.2%)

0.60

GVHD

48 (53.3%)

39 (33.9%)

0.13

Days on Voriconazole (median)

37.5

51

0.35

Mg/kg/dose

2.4

2.5

0.51

Fungal infection

16 (17.8%)

10 (16.9%)

0.99

 Timing of Fungal Infection +Day (median)

188

264

0.54

Changed to another agent

34 (62.2%)

22 (62.7%)

1.00

Death

54 (40%)

28 (52.5%)

0.18

Conclusion: Voriconazole serum levels vary widely in this patient population and higher weight based dosing does not consistently achieve therapeutic levels.. Breakthrough infections do occur with sub-therapeutic levels, but it is difficult to predict with what frequency.

Andrea Zimmer, MD, Infectious Diseases-Transplant, Mayo Clinic, Rochester, MN and John Wilson, MD, FIDSA, Infectious Disease, Mayo Clinic, Rochester, MN

Disclosures:

A. Zimmer, None

J. Wilson, None

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