AUTHOR=Li Weiyang , Xia Fan , Zhou Haixia , Qiu Huiying , Wu Depei , Ma Xiao , Sun Aining 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00349

DOI=10.3389/fmicb.2020.00349

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies.</p></sec><sec><title>Objective</title><p>To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects.</p></sec><sec><title>Patients and Methods</title><p>A total of 74 patients treated with induction chemotherapy (<italic>n</italic> = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (<italic>n</italic> = 64), who received PCZ prophylactically as an oral suspension for &gt;7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed.</p></sec><sec><title>Results</title><p>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 &lt; 0.47 μg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses.</p></sec><sec><title>Conclusion</title><p>The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of &gt;0.47 μg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT.</p></sec><sec><title>Clinical Trial Registration</title><p>Chinese Clinical Trial Registry: ChiCTR1900026294.</p></sec>