目的:通过网状Meta分析,评价四种两性霉素B静脉剂型在治疗真菌感染方面的疗效和安全性。方法:检索中英文电子数据库(PubMed、Scopus、Web of Science、the Cochrane Library、Embase、中国知网、万方数据库、维普数据库和中国生物医学...目的:通过网状Meta分析,评价四种两性霉素B静脉剂型在治疗真菌感染方面的疗效和安全性。方法:检索中英文电子数据库(PubMed、Scopus、Web of Science、the Cochrane Library、Embase、中国知网、万方数据库、维普数据库和中国生物医学文献数据库),纳入比较两性霉素B与三唑类或棘白菌素类药物治疗真菌感染的随机对照试验(RCT)进行网状Meta分析。检索时间为建库至2023年8月5日,文献质量采用GRADE分级。结果:共纳入16篇文献,涉及4365例患者。在疗效方面,两性霉素B脂质体>两性霉素B脱氧胆酸盐>两性霉素B胶体分散体,差异有统计学意义(P<0.05),两性霉素B脂质体复合物与其他剂型相比差异暂无统计学意义(P>0.05);在总不良反应发生率方面,四种两性霉素B静脉剂型的差异无统计学意义(P>0.05)。亚组分析结果显示,两性霉素B脱氧胆酸盐相比两性霉素B胶体分散体具有更高的神经系统毒性,差异有统计学意义(P<0.05)。结论:四种两性霉素B静脉剂型中,脂质体剂型的疗效优于脱氧胆酸盐传统剂型;胶体分散体剂型的疗效显著低于传统剂型,同时神经系统毒性也较低。由于研究纳入文献数量有限,可能存在发表偏倚,故仍需更多大样本量、高质量的临床研究进一步证实本研究的结果和结论。展开更多
目的探讨脱氧胆酸盐两性霉素B在重症侵袭性真菌感染患者体内药代动力学(pharmacokinetics,PK)特点及目标靶值并分析其PK变化的影响因素。方法选取从2018年11月—2022年11月在东南大学附属中大医院重症医学科就诊并接受脱氧胆酸盐两性霉...目的探讨脱氧胆酸盐两性霉素B在重症侵袭性真菌感染患者体内药代动力学(pharmacokinetics,PK)特点及目标靶值并分析其PK变化的影响因素。方法选取从2018年11月—2022年11月在东南大学附属中大医院重症医学科就诊并接受脱氧胆酸盐两性霉素B输入治疗的重症侵袭性真菌病患者。用药从1 mg/d开始逐渐累加至50 mg/d,持续静脉泵入6 h,在用药第7、14天采集给药前及给药后1、3、6、9、12 h的外周血2 mL,采用液相色谱与串联质谱联用(liquid chromatography tandem mass spectrometry,LC-MS/MS)法测定血浆中两性霉素B的浓度。观察两性霉素B的PK特点并采用线性回归法,分析影响其PK变化的影响因素。结果共纳入12例重症侵袭性真菌病患者,对比正常受试者中得到的脱氧胆酸盐两性霉素B的药代动力学参数,重症侵袭性真菌感染(invasive fungal infection,IFI)患者体内两性霉素B的谷浓度(Cmin)、清除率(clearance,CL)、半衰期(t_(1/2))和浓度时间曲线下面积(area under concentration-time curve,AUC)均高于健康受试者(均P<0.05),而血药浓度峰值(Cmax)(1.63±0.77)mg/L未见明显差异。更快的两性霉素B剂量累加速度相比于正常累加组无明显的不良反应发生率(均P>0.05)变化,并且其Cmax和表观分布容积(apparent volume of distribution,Vd)更高。单因素分析显示实时APACHEⅡ评分可能是两性霉素B峰浓度的影响因素(P=0.008)。结论重症IFI患者体内两性霉素B的谷浓度、CL、半衰期(t_(1/2))、和AUC均高于健康受试者,但Cmax两组未见明显差异,实时APACHEⅡ评分可能是影响两性霉素B峰浓度的影响因素。更快的两性霉素B药物累加速度未表现出明显的即刻不良反应发生率的增加,并且存在更高的药效浓度。展开更多
BACKGROUND In recent years,the incidence of fungal infection has been increasing,often invading one or more systems of the body.However,it is rare for lymph nodes to be invaded without the involvement of other organs....BACKGROUND In recent years,the incidence of fungal infection has been increasing,often invading one or more systems of the body.However,it is rare for lymph nodes to be invaded without the involvement of other organs.CASE SUMMARY A 21-year-old man was admitted to hospital for repeated cough for 2 mo and abdominal pain for 1 mo.Physical examination revealed multiple lymph nodes enlargement,especially those in the left neck and groin.CT scan showed multiple lymph nodes enlargement in the chest,especially left lung,abdominal cavity,and retroperitoneum.The first lymph node biopsy revealed granulomatous lesions of lymph nodes,so intravenous infusion of Cefoperazone tazobactam combined with anti-tuberculosis drugs were given.Because fever and respiratory failure occurred 4 d after admission,mechanical ventilation was given,and Caspofungin and Voriconazole were used successively.However,the disease still could not be controlled.On the 11th day of admission,the body temperature reached 40° C.After mycosis of lymph nodes was confirmed by the second lymph node biopsy,Amphotericin B was given,and the patient recovered and was discharged from the hospital.CONCLUSION No fixed target organ was identified in this case,and only lymph node involvement was found.Caspofungin,a new antifungal drug,and the conventional first choice drug,Voriconazole,were ineffective,while Amphotericin B was effective.展开更多
Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for t...Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.展开更多
Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The ai...Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections （IFIs）,compared with L-AmB.Methods Electronic databases （up to July 31,2013） PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks （RRs） and 95% confidence intervals （C/s）.Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat （MITT） patients.The results showed that caspofungin produced equal efficacy in favorable overall response （RR=1.02,95% Cl 0.88-1.18; P=0.81） and mortality rate （RR=1.53,95% Cl 0.38-6.27,P=0.55）,safer in clinical adverse events （RR=0.20,95% Cl 0.08-0.54; P=0.001）,laboratory adverse events （RR=0.69,95% Cl 0.57-0.84; P=0.0002）,and discontinuation rate （RR=0.26,95% Cl 0.08-0.83,P=0.02）,compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.展开更多
文摘目的:通过网状Meta分析,评价四种两性霉素B静脉剂型在治疗真菌感染方面的疗效和安全性。方法:检索中英文电子数据库(PubMed、Scopus、Web of Science、the Cochrane Library、Embase、中国知网、万方数据库、维普数据库和中国生物医学文献数据库),纳入比较两性霉素B与三唑类或棘白菌素类药物治疗真菌感染的随机对照试验(RCT)进行网状Meta分析。检索时间为建库至2023年8月5日,文献质量采用GRADE分级。结果:共纳入16篇文献,涉及4365例患者。在疗效方面,两性霉素B脂质体>两性霉素B脱氧胆酸盐>两性霉素B胶体分散体,差异有统计学意义(P<0.05),两性霉素B脂质体复合物与其他剂型相比差异暂无统计学意义(P>0.05);在总不良反应发生率方面,四种两性霉素B静脉剂型的差异无统计学意义(P>0.05)。亚组分析结果显示,两性霉素B脱氧胆酸盐相比两性霉素B胶体分散体具有更高的神经系统毒性,差异有统计学意义(P<0.05)。结论:四种两性霉素B静脉剂型中,脂质体剂型的疗效优于脱氧胆酸盐传统剂型;胶体分散体剂型的疗效显著低于传统剂型,同时神经系统毒性也较低。由于研究纳入文献数量有限,可能存在发表偏倚,故仍需更多大样本量、高质量的临床研究进一步证实本研究的结果和结论。
文摘目的探讨脱氧胆酸盐两性霉素B在重症侵袭性真菌感染患者体内药代动力学(pharmacokinetics,PK)特点及目标靶值并分析其PK变化的影响因素。方法选取从2018年11月—2022年11月在东南大学附属中大医院重症医学科就诊并接受脱氧胆酸盐两性霉素B输入治疗的重症侵袭性真菌病患者。用药从1 mg/d开始逐渐累加至50 mg/d,持续静脉泵入6 h,在用药第7、14天采集给药前及给药后1、3、6、9、12 h的外周血2 mL,采用液相色谱与串联质谱联用(liquid chromatography tandem mass spectrometry,LC-MS/MS)法测定血浆中两性霉素B的浓度。观察两性霉素B的PK特点并采用线性回归法,分析影响其PK变化的影响因素。结果共纳入12例重症侵袭性真菌病患者,对比正常受试者中得到的脱氧胆酸盐两性霉素B的药代动力学参数,重症侵袭性真菌感染(invasive fungal infection,IFI)患者体内两性霉素B的谷浓度(Cmin)、清除率(clearance,CL)、半衰期(t_(1/2))和浓度时间曲线下面积(area under concentration-time curve,AUC)均高于健康受试者(均P<0.05),而血药浓度峰值(Cmax)(1.63±0.77)mg/L未见明显差异。更快的两性霉素B剂量累加速度相比于正常累加组无明显的不良反应发生率(均P>0.05)变化,并且其Cmax和表观分布容积(apparent volume of distribution,Vd)更高。单因素分析显示实时APACHEⅡ评分可能是两性霉素B峰浓度的影响因素(P=0.008)。结论重症IFI患者体内两性霉素B的谷浓度、CL、半衰期(t_(1/2))、和AUC均高于健康受试者,但Cmax两组未见明显差异,实时APACHEⅡ评分可能是影响两性霉素B峰浓度的影响因素。更快的两性霉素B药物累加速度未表现出明显的即刻不良反应发生率的增加,并且存在更高的药效浓度。
文摘BACKGROUND In recent years,the incidence of fungal infection has been increasing,often invading one or more systems of the body.However,it is rare for lymph nodes to be invaded without the involvement of other organs.CASE SUMMARY A 21-year-old man was admitted to hospital for repeated cough for 2 mo and abdominal pain for 1 mo.Physical examination revealed multiple lymph nodes enlargement,especially those in the left neck and groin.CT scan showed multiple lymph nodes enlargement in the chest,especially left lung,abdominal cavity,and retroperitoneum.The first lymph node biopsy revealed granulomatous lesions of lymph nodes,so intravenous infusion of Cefoperazone tazobactam combined with anti-tuberculosis drugs were given.Because fever and respiratory failure occurred 4 d after admission,mechanical ventilation was given,and Caspofungin and Voriconazole were used successively.However,the disease still could not be controlled.On the 11th day of admission,the body temperature reached 40° C.After mycosis of lymph nodes was confirmed by the second lymph node biopsy,Amphotericin B was given,and the patient recovered and was discharged from the hospital.CONCLUSION No fixed target organ was identified in this case,and only lymph node involvement was found.Caspofungin,a new antifungal drug,and the conventional first choice drug,Voriconazole,were ineffective,while Amphotericin B was effective.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
文摘Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B （L-AmB）.However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections （IFIs）,compared with L-AmB.Methods Electronic databases （up to July 31,2013） PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks （RRs） and 95% confidence intervals （C/s）.Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat （MITT） patients.The results showed that caspofungin produced equal efficacy in favorable overall response （RR=1.02,95% Cl 0.88-1.18; P=0.81） and mortality rate （RR=1.53,95% Cl 0.38-6.27,P=0.55）,safer in clinical adverse events （RR=0.20,95% Cl 0.08-0.54; P=0.001）,laboratory adverse events （RR=0.69,95% Cl 0.57-0.84; P=0.0002）,and discontinuation rate （RR=0.26,95% Cl 0.08-0.83,P=0.02）,compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.
文摘目的:分析低剂量两性霉素B(amphotericin B,AmB)在接受化疗后的恶性血液病患者不同抗真菌策略下的疗效及安全性。方法:收集2013年5月-2015年5月收治于解放军总医院应用低剂量AmB患者的病历资料,进行回顾性分析,比较各种治疗策略下的有效率,并对用药前后肾功能及电解质变化情况进行统计学分析,评价其安全性。结果:在全部97例次患者中,确诊为侵袭性真菌病(invasive fungal disease,IFD)患者2例次,临床诊断为IFD患者11例次,拟诊IFD患者15例次,未确定IFD患者69例次,低剂量AmB对全部患者的有效率为69.4%,目标治疗72.7%,诊断驱动治疗63.6%,经验治疗75%,联合其他抗真菌药物的有效率分别是50%、66.7%、75%。统计所有应用AmB患者仅有7例次(7.2%)肌酐(Cr)水平升高超过正常值上限,且均在停药7 d内恢复正常。虽然停药后1 d血清Cr水平较用药前有所增加(64.86±3.00 vs 58.76±1.67μmol/L),差异具有统计学意义(P<0.05),但停药后7 d Cr水平与用药前相比无明显变化(58.43±1.68μmol/L,P>0.05)。结论:应用低剂量AmB对于粒细胞缺乏而应用广谱抗生素无效的持续发热患者进行经验性或诊断驱动治疗是一种安全有效的措施。
