Detailed Antifungal Stewardship (AFS) is Key to Achieving Excellent Plasma Levels During Oral Posaconazole (PCZ) Prophylaxis in High Risk Hematology Patients

Ref ID: 19256

Author:

N. H. Hewitt, K. F. Urbancic, A. P. Grigg, M. L. Grayson

Author address:

Austin Hosp., Melbourne, AUSTRALIA

Full conference title:

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy

Date: 10 September 2014

Abstract:

Background: Oral PCZ is effective antifungal prophylaxis in high risk neutropenic patients. However, achieving adequate plasma PCZ levels can be problematic due to variable absorption with the current formulation. The role of AFS and therapeutic drug monitoring (TDM) for PCZ prophylaxis remains controversial. Methods: Since August, 2011, all high risk hematology patients receiving PCZ prophylaxis were prospectively managed within a detailed AFS program to ensure PCZ compliance and TDM, and to optimize absorption. All patients who received ≥ 7 days PCZ prophylaxis and had ≥ 1 PCZ level (via HPLC assay) were reviewed. Demographics, known factors associated with poor PCZ absorption (age, diarrhea, mucositis, and proton pump inhibitor [PPI] administration) and rates of proven or probable invasive fungal infection (IFI) as per EORTC/MSG criteria were studied. Results: Of 61 patients, 53 (46 AML/MDS; 3 ALL; 4 other) had a total of 93 PCZ prophylaxis courses, with 111 PCZ levels measured. Mean trough PCZ levels were 0.83±0.43mg/L (median 0.75; range <0.1-2.15), with 7/93 (8%) <0.3mg/L, 17/93 (18%) <0.5mg/L and 41/93 (44%) <0.7mg/L. Factors associated with low (<0.3mg/L) PCZ levels included: PPI administration (p=0.03), diarrhea (p=0.004), collective gastrointestinal intolerance (nausea, vomiting, diarrhea, poor oral intake, and/or mucositis) (p=0.02) and age 8804;60 years (p=0.01). Among the 7 patients with PCZ levels <0.3mg/L, AFS resulted in improved levels or change in prophylaxis regimen in 71%. IFI was identified in only 2 cases (proven) - both of whom had levels >0.5mg/L. Implementation of the AFS required
0.3 EFT specialist pharmacist, but saved approx. twice this
salary cost in improved antifungal use. Conclusions: AFS
is highly effective in ensuring generally excellent levels
with PCZ prophylaxis. We identified similar risk factors to
others for low PCZ levels, but found that these can be
effectively managed to achieve good outcomes. Although
some have questioned the role of TDM for PCZ prophylaxis,
we found it a useful component of effective AFS for high
risk hematology patients.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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