伊曲康唑预防血液病患者肺部侵袭性真菌感染的临床研究

Clinical Research on Ltraconazole in Prevention of Pulmonary Invasive Fungal Infection( IFI) in Patients with Hemopathy

目的 探讨伊曲康唑不同给药方案用于急性髓系白血病患者肺部侵袭性真菌感染（IFI）的临床效果及安全性。方法 选取血液科2013年1月~2014年12月收治的行诱导化疗和巩固化疗的35例急性髓系白血病患者为研究对象,35例患者共进行97例次化疗,将97例次随机分为口服液组48例次和贯序组49例次,口服液组患者给予伊曲康唑口服液预防肺部侵袭性真菌感染,贯序组患者前2天给予伊曲康唑静脉给药,之后给予伊曲康唑口服液维持,最长用药均为6周,监测两组患者血药浓度,观察两组患者IFI预防有效率、不良反应及严重程度。结果 贯序组患者IFI预防有效率（93.9%）显著高于口服液组（79.2%）（χ2=4.251 P=0.033）;贯序组伊曲康唑稳态血药浓度（698.2±99.5）ng/m L显著高于口服液组（573.5±78.3）ng/m L（t=6.850 P〈0.001）;贯序组患者伊曲康唑血药浓度达到500 ng/m L的时间（3.4±1.0）天,明显低于口服液组（7.8±2.2）天（t=12.726 P〈0.001）。贯序组患者维持稳态血药浓度的时间（11.2±2.9）天明显高于口服液组（6.7±1.6）（t=9.836 P〈0.001）;两组患者因不良反应退出研究比例（14.6%vs.18.4%）差异无统计学意义（χ2=0.252 P=0.616）。结论伊曲康唑预防急性髓性白血病患者粒细胞缺乏期侵袭性真菌感染的效果与血药浓度密切相关,静脉±口服液的贯序方案效果优于单纯口服液方案。

Objective To explore clinical efficacy and safety of different dosing itraconazole regimens in prevention of pulmonary IFI in acute myeloid leukemia. Methods 35 cases of acute myeloid leukemia patients underwent chemothera- py and consolidation chemotherapy of January 2013 to December 2014 in our hospital were selected as study objects, all cases with a total of 97 case time of chemotherapy, which were randomly assigned to oral liquid group （48 cases ） and sequential treatment group （49 cases）, oral liquid group were treated with itraconazole oral liquid for prevention of pulmonary IFI, sequential treatment was given itraconazole intravenously for the first 2 days , after which maintained with itraconazole oral liquid , all cases with the longest administration for 6 weeks, blood itraconazole concentration was monitored during treatment, and effective prevention ratio for IFI, adverse reactions and severity were noted. Results Sequential treatment group whose IFI prevention efficiency （93.9%） was significantly higher than oral liquid group （79.2%） （X2 =4. 251 P = 0. 033 ）; Sequential treatment group whose steady -state blood itraconazole concentration （698.2 ±99. 5 ） ng/mL was significantly higher than oral liquid group （57. 35 ±78.3 ） ng/mL （ t = 6. 850 P 〈 0. 001 ） ; Patients in sequential treatment group whose time course of blood itraconazole concentration reached to 500 ng/mL （ 3.4 ± 1. 0） d was significantly lower than oral liquid group （7. 8 ±2. 2）d （t = 12. 726 P 〈0. 001 ）. Sequential treatment group who maintained steady blood itraconazole concentration course （ 11.2 ± 2. 9） d was significantly higher than oral liquid group （6. 7±1.6） （ t = 9. 836 P 〈 0. 001 ）. Two groups whose proportion withdrew from the study （ 14. 6% vs. 18.4% ） due to adverse reactions with no statistical differences （X2 = 0. 252 P = 0. 616）. Conclusions Clinical efficacy of itraconazole in preventive of pulmonary IFI of acute myeloid leukemia with granulocyte deficiency stage is closely related to blood drug concentration, efficacy of intravenous plus oral liquid regimen is superior to simple oral liquid regimen.