摘要
目的探索泊沙康唑在应用糖皮质激素(GC)治疗的肝衰竭患者中预防侵袭性肺曲霉病(IPA)的有效性及安全性。方法本研究为观察性研究。纳入2016年2月至2022年2月在河北医科大学第三医院感染科住院治疗的应用GC的早中期肝衰竭患者。根据治疗期间是否使用泊沙康唑分为试验组[使用泊沙康唑混悬液(200 mg/次,每天3次)]和对照组(未使用泊沙康唑)。两组患者按照年龄、性别、基线终末期肝病模型评分1∶2匹配,收集患者基本信息、实验室检查结果、泊沙康唑药物不良反应、侵袭性曲霉感染发生情况、治疗效果。统计学分析采用χ^(2)检验,logistic回归分析影响IPA的危险因素,采用受试者操作特征曲线分析危险因素的预测价值,Kaplan-Meier生存曲线分析患者生存情况,Log-rank检验比较试验组和对照组生存率。结果共纳入患者108例,其中试验组36例,对照组72例。两组肝病病因、基线实验室检查结果、可能影响侵袭性曲霉感染的危险因素等方面差异均无统计学意义(均P>0.05)。住院期间21例发生IPA,总感染率为19.4%(21/108),试验组为5.6%(2/36),对照组为26.4%(19/72),两组IPA发生率的差异有统计学意义(χ^(2)=6.65,P=0.010)。logistic回归分析结果提示C反应蛋白升高、GC应用>7 d、GC累积剂量是应用GC治疗肝衰竭患者并发IPA的独立危险因素(比值比分别为1.080、15.266、1.004,均P<0.05),受试者操作特征曲线示C反应蛋白截断值为6.00 mg/L,GC累积剂量截断值为490 mg。试验组和对照组患者发生中性粒细胞计数减少,血小板计数减少,消化道出血,恶心、呕吐的比例差异均无统计学意义(均P>0.05),均无视觉障碍及停止用药患者。累计死亡20例(18.5%),存活88例(81.5%)。21例IPA患者中,死亡11例(52.4%);87例未发生IPA患者中,累计死亡9例(10.3%)。发生和未发生IPA患者的生存率差异有统计学意义(χ^(2)=21.31,P<0.001)。结论泊沙康唑可能有助于降低应用GC治疗的肝衰竭患者并发IPA的发生率,提高肝衰竭患者生存率,且不良反应少见。
Objective To investigate the efficacy and safety of posaconazole in the prevention of invasive pulmonary aspergillosis(IPA)in patients with liver failure treated with glucocorticoids(GC).Methods The study was an observational study.Patients with early and middle stages of liver failure hospitalized in the Department of Infectious Diseases of Hebei Medical University Third Hospital,who received GC treatment between February 2016 and February 2022 were included.The patients were divided into trial group(with posaconazole suspension(200 mg each time,three times daily))and control group(without posaconazole)according to whether posaconazole was used during treatment.Two groups of patients were matched of 1∶2 ratio according to age,gender and baseline model for end-stage liver disease(MELD)score.The basic information,laboratory examination results,adverse reactions of posaconazole,incidence of invasive Aspergillus infection and therapeutic effect of patients were collected.Statistical analysis was performed using the chi-square test,logistic regression analysis was used to screen risk factors for IPA,the receiver operator characteristic(ROC)curve was used to evaluate the predictive ability of the risk factors,Kaplan-Meier survival curves was used to analyze patient′s survival,and Log-rank test was used to compare the survival rates between the trial group and control group.Results A total of 108 patients(36 in trial group and 72 in control group)were enrolled.There were no statistical differences between the two groups in terms of the etiology of liver diseases,baseline laboratory findings and risk factors for invasive Aspergillus infection(all P>0.05).There were 21 cases of IPA during hospitalization,with a total infection rate of 19.4%(21/108),including 5.6%(2/36)in the trial group and 26.4%(19/72)in the control group.The difference of IPA incidences between the two groups was statistically significant(χ^(2)=6.65,P=0.010).Logistic regression analysis suggested that elevated C-reactive protein,GC application more than seven days and cumulative dose of GC were independent risk factors for IPA in patients with liver failure treated with GC(odds ratio(OR)=1.080,15.266,1.004,respectively,all P<0.05).The ROC curve showed that the cut-off value of C-reactive protein was 6.00 mg/L,and cumulative dose of GC was 490 mg.There were no statistical differences between the two groups in terms of adverse effects such as neutropenia,thrombocytopenia,gastrointestinal bleeding,nausea and vomiting rates(all P>0.05),and there were no patients with visual disturbances or discontinuation of medication.Cumulative deaths were 20(18.5%),and 88(81.5%)patients survived in this study.There were 11(52.4%)deaths among 21 patients with IPA and nine(10.3%)deaths among 87 patients without IPA.The difference of survival rates between patients who developed and did not develop IPA was statistically significant(χ^(2)=21.31,P<0.001).Conclusions Posaconazole may be helpful in reducing the incidence of concurrent IPA morbidity in patients with liver failure treated with GC,thereby improving survival rates with few adverse effects.
作者
谢婧
申川
李子月
方翔宇
赵彩彦
Xie Jing;Shen Chuan;Li Ziyue;Fang Xiangyu;Zhao Caiyan(Department of Infectious Diseases,Hebei Medical University Third Hospital,Shijiazhuang 050000,China)
出处
《中华传染病杂志》
CAS
CSCD
2023年第11期706-713,共8页
Chinese Journal of Infectious Diseases
基金
河北省政府资助临床医学优秀人才培养项目(ZF2024092)。
