Background: Posaconazole therapeutic drug monitoring (TDM) is recommended to promote effective antifungal prophylaxis, but its utility has yet to be optimized. Breakthrough invasive fungal infections have been reported with serum concentrations <700 mcg/L, but there is little evidence to determine the optimal serum concentration for efficacy or concentrations associated with toxicity. Challenges for effective monitoring are greater in settings without posaconazole TDM facilities because of the long turnaround time before receipt of results.
Methods: Thirty-eight TDM episodes were performed on 18 patients in a regional center in Australia during a 30-month period. Australian guidelines recommend a trough serum concentration of ≥700 mcg/L. The response to concentrations below the recommendation threshold (700 mcg/L), the final serum plasma concentration for each patient, and the appropriateness of TDM were evaluated.
Results: A total of 19 (50%) concentrations were recorded to be < 700 mcg/L. Of these 19 concentrations, the drug dose was increased on only 4 occasions. Eleven of 18 patients (61%) had initial concentrations <700 mcg/L, with only 3 (27%) among those achieving final concentration ≥ 700 mcg/L; 5 patients with initial concentrations <700 mcg/L did not have any further TDM testing. Nine of the 18 (50%) patients had a final concentration <700 mcg/L. Five of 7 (71%) patients with initial concentrations ≥700 mcg/L had further TDM with no reasoning documented.
Conclusions: The results demonstrate a lack of confidence and consistency in ordering, interpreting, and following up posaconazole concentrations. Therefore, the use of TDM should be carefully considered, especially in regional centers. Such settings should consider the practicalities of posaconazole TDM and try to improve the process to ensure consistency and optimization of patient care.