泊沙康唑预防血液病患者侵袭性真菌感染的效果及影响因素

Efficacy of posaconazole on preventing invasive fungal disease in patients with hematological disease and its influencing factors

目的 观察血液病患者应用泊沙康唑预防侵袭性真菌病(IFD)的效果,探讨预防后发生IFD突破的影响因素。方法 回顾性分析2018年10月1日—2020年12月31日河南省10家医院203例应用泊沙康唑预防IFD的血液病患者的临床资料,其中化疗患者91例,造血干细胞移植患者112例。化疗、造血干细胞移植当天或入院后出现外周血中性粒细胞计数减少(<0.5×10^(9)/L)时给予泊沙康唑口服预防IFD,记录预防治疗4 d以上或停药后7 d内确诊/临床诊断/拟诊IFD(PPP-IFD)及未确定IFD发生情况。发生PPP-IFD或未确定IFD者为IFD突破,IFD突破后启动抗真菌治疗,继续给予泊沙康唑口服或经验性联合伏立康唑、卡泊芬净、两性霉素B。比较不同年龄、性别、原发病、合并症、IFD感染史、血液病治疗方法、泊沙康唑预防时机、泊沙康唑预防疗程及中性粒细胞计数减少>2周、使用胃肠外营养等临床特征的化疗、造血干细胞移植患者IFD突破发生率。采用多因素Cox回归分析化疗、造血干细胞移植的血液病患者应用泊沙康唑预防IFD后发生IFD突破的影响因素。结果 (1)203例患者IFD突破发生率为17.73%,其中化疗患者13例,造血干细胞移植患者23例。(2)中性粒细胞计数减少≤2周(3.30%)、泊沙康唑预防疗程≥2周(3.30%)的化疗患者IFD突破发生率低于中性粒细胞计数减少>2周(10.99%)、泊沙康唑预防疗程<2周(10.99%)者(P<0.05),不同性别、年龄、泊沙康唑预防时机、化疗类型及有无合并症、IFD感染史、胃肠外营养的化疗患者IFD突破发生率比较差异均无统计学意义(P>0.05)。泊沙康唑预防疗程(HR=1.643,95%CI:0.074~2.467,P=0.027)是化疗的血液病患者泊沙康唑预防后发生IFD突破的影响因素。(3)有IFD感染史(16.07%)、糖皮质激素剂量>2 mg/(kg·d)(11.61%)、泊沙康唑预防疗程<4周(11.61%)的造血干细胞移植患者IFD突破发生率高于无IFD感染史(4.46%)、糖皮质激素剂量≤2 mg/(kg·d)(8.93%)、泊沙康唑预防疗程≥4周(8.93%)者(P<0.05),不同性别、年龄、移植类型、泊沙康唑预防时机、中性粒细胞减少天数、有无合并症及是否使用胃肠外营养、抗胸腺细胞球蛋白的造血干细胞移植患者IFD突破发生率比较差异均无统计学意义(P>0.05)。IFD感染史(HR=6.062,95%CI:4.068~8.640,P=0.003)、泊沙康唑预防疗程(HR=2.526,95%CI:1.202~3.331,P<0.001)是造血干细胞移植的血液病患者泊沙康唑预防后发生IFD突破的影响因素。结论 泊沙康唑可有效预防血液病患者发生IFD感染,有IFD感染史的造血干细胞移植患者应警惕IFD突破的发生,血液病患者延长泊沙康唑预防疗程有助于减少IFD突破的发生。

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(<0.5×10^(9)/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.O01)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.