STUDY OBJECTIVE: To evaluate the incidence of posaconazole serum levels below 700 μg/L, the rate of breakthrough infections during posaconazole prophylaxis, and factors influencing posaconazole exposure in daily clinical practice. DESIGN: Prospective observational study and review of the literature. SETTING: Hematology and oncology department in a tertiary care academic medical center. PATIENTS: A total of 31 patients with hematologic diseases: 27 received posaconazole prophylaxis and 4 received posaconazole therapy. MEASUREMENTS AND MAIN RESULTS: We analyzed 187 posaconazole serum levels from 31 patients (median of five posaconazole levels per patient; range 1-16). The analyses revealed that 80 of 187 levels (43%) were below 700 μg/L, and 68% of patients were found to have at least one measured level below this threshold. Breakthrough invasive fungal infections categorized as probable or possible infections occurred in 4 of 27 patients (15%) receiving the drug as prophylaxis. A multivariate analysis, accounting for repeated measurements per patient, revealed that age (p=0.02) and mucositis (p=0.04) were associated with significantly reduced posaconazole serum levels. A review of the current literature on posaconazole therapeutic drug monitoring data from real-world studies is presented as an overview table, highlighting the frequency of patients with inadequate posaconazole exposure and heterogeneity of factors influencing posaconazole levels. CONCLUSION: Therapeutic drug monitoring of posaconazole is an important tool of therapy optimization because oral posaconazole suspension shows unreliable absorption rates and exposure.
STUDY OBJECTIVE: To evaluate the incidence of posaconazole serum levels below 700 μg/L, the rate of breakthrough infections during posaconazole prophylaxis, and factors influencing posaconazole exposure in daily clinical practice. DESIGN: Prospective observational study and review of the literature. SETTING: Hematology and oncology department in a tertiary care academic medical center. PATIENTS: A total of 31 patients with hematologic diseases: 27 received posaconazole prophylaxis and 4 received posaconazole therapy. MEASUREMENTS AND MAIN RESULTS: We analyzed 187 posaconazole serum levels from 31 patients (median of five posaconazole levels per patient; range 1-16). The analyses revealed that 80 of 187 levels (43%) were below 700 μg/L, and 68% of patients were found to have at least one measured level below this threshold. Breakthrough invasive fungal infections categorized as probable or possible infections occurred in 4 of 27 patients (15%) receiving the drug as prophylaxis. A multivariate analysis, accounting for repeated measurements per patient, revealed that age (p=0.02) and mucositis (p=0.04) were associated with significantly reduced posaconazole serum levels. A review of the current literature on posaconazole therapeutic drug monitoring data from real-world studies is presented as an overview table, highlighting the frequency of patients with inadequate posaconazole exposure and heterogeneity of factors influencing posaconazole levels. CONCLUSION: Therapeutic drug monitoring of posaconazole is an important tool of therapy optimization because oral posaconazole suspension shows unreliable absorption rates and exposure.
Authors: Sibylle C Mellinghoff; Jens Panse; Nael Alakel; Gerhard Behre; Dieter Buchheidt; Maximilian Christopeit; Justin Hasenkamp; Michael Kiehl; Michael Koldehoff; Stefan W Krause; Nicola Lehners; Marie von Lilienfeld-Toal; Annika Y Löhnert; Georg Maschmeyer; Daniel Teschner; Andrew J Ullmann; Olaf Penack; Markus Ruhnke; Karin Mayer; Helmut Ostermann; Hans-H Wolf; Oliver A Cornely Journal: Ann Hematol Date: 2017-12-07 Impact factor: 3.673
Authors: Whitley M Yi; Kelly E Schoeppler; Jaclyn Jaeger; Scott W Mueller; Robert MacLaren; Douglas N Fish; Tyree H Kiser Journal: Ann Clin Microbiol Antimicrob Date: 2017-09-11 Impact factor: 3.944