Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

Weiyang Li; Fan Xia; Haixia Zhou; Huiying Qiu; Depei Wu; Xiao Ma; Aining Sun

doi:10.3389/fmicb.2020.00349

Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

Front Microbiol. 2020 Mar 19:11:349. doi: 10.3389/fmicb.2020.00349. eCollection 2020.

Authors

Weiyang Li¹, Fan Xia², Haixia Zhou¹, Huiying Qiu¹, Depei Wu¹, Xiao Ma¹, Aining Sun¹

Affiliations

¹ Department of Hematology, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

Background: Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies.

Objective: To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects.

Patients and methods: A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed.

Results: The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25-1.0 μg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 μg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses.

Conclusion: The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT.

Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1900026294.

Keywords: Chinese hematology patients; antifungal prophylaxis; invasive fungal infection; posaconazole; serum drug concentration.