Efficacy of posaconazole on preventing invasive fungal disease in patients with hematological disease and its influencing factors
Objective To observe the efficacy of posaconazole on preventing invasive fungal disease(IFD)in patients with hematological diseases,and to investigate the influencing factors of IFD breakthrough after posaconazole prophylaxis.Methods Totally 203 patients received posaconazole to prevent IFD in 10 hospitals in Henan province from October 1,2018 to December 31,2018,among whom 91 patients received chemotherapy and 112 received hematopoietic stem cell transplantation(HSCT)for hematological diseases,and their clinical data were retrospectively analyzed.The patients were given oral posaconazole for preventing IFD on the day of chemotherapy and HSCT,or on the day of decreased absolute neutrophil count(＜0.5X109/L)after admission.The occurrence of proven/probable/possible IFD(PPP-IFD)and undefined IFD was recorded after posaconazole prophylaxis over 4 d or within 7 d after discontinuation of medication.After IFD breakthrough(occurrence of PPP-IFD or undefined IFD),antifungal therapy was initiated with continuous use of oral posaconazole or combined empirical treatment with voriconazole,caspofungin,or amphotericin B.The incidences of IFD breakthrough were compared among patients with different ages,genders,primary diseases,comorbidities,history of IFD,hematological disease treatment methods,timing and course of posaconazole prophylaxis,course of decreased neutrophil count＞2 weeks,and use of parenteral nutrition after chemotherapy and HSCT patients.Multivariate Cox regression analysis was conducted to identify the influencing factors of IFD breakthrough in patients undergoing chemotherapy and HSCT after posaconazole prophylaxis.Results(1)The incidence of IFD breakthrough was 17.73％,including 13 chemotherapy patients and 23 HSCT patients.(2)In chemotherapy patients,the incidences of IFD breakthrough were lower in those with course of decreased absolute neutrophil count ≤ 2 weeks and posaconazole prophylaxis course ≥2 weeks(3.30％,3.30％)than those in patients with course of decreased absolute neutrophil count＞14 d and posaconazole prophylaxis course＜2 weeks(10.99％,10.99％)(P＜0.05),and there were no significant differences in the incidences of IFD breakthrough in patients with different genders,ages,timing of posaconazole prophylaxis and chemotherapy types,and between patients with and without comorbidities,history of IFD and parenteral nutrition(P＞0.05).The posaconazole prophylaxis course(HR=1.643,95％CI:0.074-2.467,P=0.027)was an influencing factor of the occurrence of IFD breakthrough.(3)In HSCT patients,the incidences of IFD breakthrough were higher in those with IFD history,glucocorticoids dosage＞2 mg/(kg·d),and posaconazole prophylaxis course＜4 weeks(16.07％,11.61％,11.61％)than those in patients with no IFD history,glucocorticoids dosage ≤2 mg/(kg·d)and posaconazole prophylaxis course ≥4 weeks(4.46％,8.93％,8.93％)(P＜0.05).There were no significant differences in the incidences of IFD breakthrough in patients with different genders,ages,transplantation types,timing of posaconazole prophylaxis and course of decreased absolute neutrophil count,and between patients with and without comorbidities,parenteral nutrition and anti-thymocyte globulin(P＞0.05).IFD history(HR=6.062,95％CI:4.068-8.640,P=0.003)and posaconazole prophylaxis course(HR=2.526,95％CI:1.202-3.331,P＜0.001)were the influencing factors of IFD breakthrough after posaconazole prophylaxis.Conclusions Posaconazole can effectively prevent IFD in patients with hematological diseases.IFD breakthrough should be prevented in HSCT patients with a history of IFD.To prolong the course of posaconazole prophylaxis can reduce the occurrance of IFD breakthrough in patients with hematological diseases.
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