552 - Comparison of Therapeutic Drug Levels of Adult and Pediatric Patients Undergoing Treatment for Fungal Diseases

Abstract

Background: The mortality of invasive fungal infections is significant, indicating the critical need for appropriate treatment and dosing of anti-fungal drugs. Variable absorption and pharmacokinetics of triazole antifungal drugs (e.g. posaconazole and voriconazole) create a challenge for physicians to consistently achieve blood levels in the therapeutic range, particularly in patients suffering from comorbidities. The use of therapeutic drug monitoring (TDM) is critical for ensuring efficacy of voriconazole (VOR) and posaconazole (POS) treatment. Dosing in pediatric patients can prove more difficult because there have been fewer studies in these patient populations. Methods: Drug levels of POS and VOR were determined by reverse phase LC MS/MS on plasma or serum samples submitted for testing. Results were de-identified and reviewed to determine whether results fell within the therapeutic range for effective anti-fungal treatment. A large sample set (POS approximately 2500 samples and VOR approximately 5500 samples) was included to reduce the chance of sample size variability. Pediatric samples were defined as those coming from patients 17 years and younger. Results: For POS, in pediatric patients, 7.5% of samples tested had drug levels below the limit of detection of the assay (.1 mcg/mL) compared to 4% in adults; and an additional 19% of samples in pediatric and 13% in adults tested had detectable levels that were below the suggested therapeutic level of .7 mcg/mL. For VOR, the percentage of samples tested with results either above or below the therapeutic window was even higher: 6.7% of adult samples and 10.8% of pediatric samples tested had drug levels below the limit of detection of the assay (.1 mcg/mL), and an additional 21.3% of adult samples and 39.2% of pediatric sample had detectable levels that were below the suggested therapeutic range of 1.0-5.5 mcg/mL. Additionally, 13.4% of adult samples and 7.7% of pediatric samples tested had levels that were above the therapeutic range. Conclusions: From these data it is clear that an alarmingly high number of both adult and pediatric patient samples tested (24% of adult and 46% of pediatric) have antifungal drug levels below the recommended therapeutic levels. These data indicate the criticality of monitoring antifungal drug levels because of the high frequency of sub-therapeutic concentrations due to variations in metabolism, absorption or even patient compliance. Moreover, 7% of VOR results demonstrated levels above the recommended therapeutic levels, putting these patients at risk for toxicity.