两性霉素B脂质体致急性肾损伤相关危险因素分析

目的统计分析两性霉素B脂质体致急性肾损伤(AKI)的发生率及相关危险因素。方法回顾性分析某三甲医院2016年1月—2018年12月使用两性霉素B脂质体患者的病历资料,记录患者基本资料和相关用药情况,采用单因素与多因素逐步logistic回归分析两性霉素B脂质体相关AKI危险因素。结果272例使用两性霉素B脂质体的患者,24例发生两性霉素B脂质体相关AKI,发生率8.8%;单因素分析显示,女性、联用环孢素、造血干细胞移植和两性霉素B脂质体累计使用量≥450 mg与AKI发生有关(P<0.1);多因素分析显示,女性和两性霉素B脂质体累计使用量≥450 mg是AKI独立危险因素(P<0.05);13例发生AKI患者停药1周后肌酐值较用药期间最高值下降(P<0.05)。结论两性霉素B脂质体致AKI较常见,用药期间应加强女性患者及累计使用剂量≥450 mg患者发生AKI的风险评估,密切监测给药期间尤其是约2周患者肌酐水平。大部分患者AKI可逆。     

两性霉素B脂质体引起低钾血症的危险因素分析

目的 探讨两性霉素B脂质体引起低钾血症的危险因素，为临床合理用药提供参考。方法 回顾性分析2012年1月至2021年12月在海南医学院第一附属医院住院期间使用两性霉素B脂质体的患者信息，收集其两性霉素B脂质体的使用详情和钾剂补充情况，按照是否发生低钾血症分成低钾血症组和正常组，采用单因素及多因素Logistic回归分析法分析两性霉素B脂质体引起低钾血症的危险因素。结果 共纳入121例患者，其中低钾血症组60例、正常组61例。低钾血症组患者的两性霉素B脂质体维持剂量、累积剂量、最大日剂量（重度低钾血症患者）、治疗天数、出现低钾血症的时间、每日补钾剂量（中、重度低钾血症患者）、总补钾天数（中度低钾血症患者）均显著高于或长于正常组（P<0.05）。单因素分析结果显示，两性霉素B脂质体累积剂量≥200mg、治疗天数≥5 d对该药引起低钾血症有显著影响（P<0.05）。多因素分析结果显示，患者存在基础低血钾、体重<50 kg、两性霉素B脂质体累积剂量≥200 mg、治疗天数≥5 d是该药引起低钾血症的独立危险因素（P<0.05）。结论 两性霉素B脂质体引起低血钾症的发生率...     

恶性血液病合并侵袭性真菌感染的治疗方案及临床分析

目的了解恶性血液病合并侵袭性真菌感染的临床现状,探讨和研究恶性血液病合并侵袭性真菌感染的易感因素、有效治疗方案及临床分析。方法将120例于2011年6月至2012年6月期间在我院进行恶性血液病合并侵袭性真菌感染治疗的患者分成三个观察组,每组40人。第一组患者使用伊曲康唑治疗;第二组患者使用氟康唑组治疗;第三组患者使用两性霉素B组治疗。对三个观察组患者的致病因素和临床治疗效果进行及时分析。结果 120例患有恶性血液病合并侵袭性真菌感染的患者的感染部位多为呼吸道感染(70.83%)和肠道感染(18.33%)。应用氟康唑组治疗合并侵袭性真菌感染的效果低于伊曲康唑和两性霉素B组;应用两性霉素B组治疗合并侵袭性真菌感染出现不良反应的概率高于氟康唑组和伊曲康唑。结论应用伊曲康唑和两性霉素B组治疗恶性血液病合并侵袭性真菌感染的效果比较明显,氟康唑组的治疗安全性优于伊曲康唑和两性霉素B组。     

卡泊芬净在器官移植术后侵袭性真菌感染病人中的应用

目的对卡泊芬净治疗器官移植术后侵袭性真菌感染的疗效进行评价。方法采用病例对照研究方法,选择我院器官移植术后出现侵袭性真菌感染病人100例,分为3组。卡泊芬净组36例,氟康唑组36例,两性霉素B组28例,分别予卡泊芬净、氟康唑和两性霉素B治疗,观察抗真菌治疗疗效。结果卡泊芬净组、氟康唑组和两性霉素B组抗真菌治疗的有效率分别为76%、81%和67%,3组疗效无显著差异(P>0.05)。卡泊芬净组与氟康唑组、两性霉素B组用药过程中的不良反应发生率分别为6%、6%和14%。结论卡泊芬净对于器官移植术后病人侵袭性真菌感染有明显的治疗作用,疗效与两性霉素B和氟康唑相当。     

59例恶性血液病患者合并侵袭性真菌病的临床分析

目的观察59例恶性血液病合并侵袭性真菌病患者的临床特征,并探讨两性霉素B脂质体联合伏立康唑治疗恶性血液病患者合并侵袭性真菌病的临床疗效及安全性。方法回顾性分析2010年至2015年入住我院血液科合并侵袭性真菌病(IFI)的恶性血液病患者59例的病例资料,依据使用抗真菌药物的不同进行分组,其中17例应用两性霉素B脂质体联合伏立康唑治疗(联合治疗组),24例单用伏立康唑治疗(伏立康唑组),18例单用两性霉素B脂质体治疗(两性霉素B脂质体组)。收集、总结临床特征、分析其治疗效果及安全性,并进行统计学分析。结果联合治疗组的有效率为82.3%,伏立康唑组的有效率为37.5%,两性霉素B脂质体组的有效率为61.1%。三组之间治疗有效率差异均有统计学意义(P0.05)。而联合治疗组的不良反应发生率为58.8%,伏立康唑组的不良反应发生率为25.0%,两性霉素B脂质体组的不良反应发生率为55.5%。结论应用两性霉素B脂质体联合伏立康唑治疗恶性血液病合并侵袭性真菌病的效果较单用伏立康唑或单用两性霉素B脂质体,可明显提高疗效,且安全性上并不比单用两性霉素B脂质体差,患者往往能够耐受。     

两性霉素B相关肝损伤发生情况及其影响因素分析

目的:探讨两性霉素B相关肝损伤的发生情况并分析其影响因素。方法:通过医院信息系统收集2013年1月至2017年12月在复旦大学附属中山医院住院期间应用两性霉素B且用药前后肝功能检查结果记录完整患者的病历资料进行回顾性分析。根据《药物性肝损伤诊治指南》进行肝损伤分型与诊断,计算两性霉素B致肝损伤发生率,并将患者按年龄(≤45、>45岁),入院前3个月内有无肝损伤/肝病史,所用两性霉素B剂型(非脂质体、脂质体)、最大日剂量(<30、≥30 mg)、最大日剂量/体重(<0.5、≥0.5 mg/kg),是否阶梯加量用药、疗程(≤21、>21 d)、累积剂量(<600、≥600 mg)、累积剂量/体重(<10、≥10 mg/kg),是否联用保肝药物,以及是否联用其他有肝毒性的药物,各分为2组,分别比较上述11项临床特征不同的2组患者应用两性霉素B后血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、碱性磷酸酶(ALP)和γ-谷氨酰转移酶(γ-GT)水平,应用多因素Logistic回归分析和多重线性回归分析方法分析两性霉素B致肝损伤的影响因素,前者效应值为比值比( OR)及其95%置信区间( CI),后者效应值为标准化回归系数及其95 %CI和 R 2值。 结果:纳入分析的患者共42例,男性31例,女性11例;年龄13~92岁;体重(65.0±12.3)kg。42例患者中,>45岁者26例;既往有肝损伤/肝病史者15例;应用两性霉素B者30例,应用两性霉素B脂质体者10例,2种剂型均应用者2例;两性霉素B最大日剂量<30 mg、最大日剂量/体重<0.5 mg/kg者25例,≥30 mg、≥0.5 mg/kg者17例;阶梯加量用药者28例,初始剂量即为最大日剂量者14例;累积剂量<600 mg、累积剂量/体重<10 mg/kg者24例,≥600 mg、≥10 mg/kg者18例;联用保肝药物者29例;联用其他有肝毒性的药物者33例。应用两性霉素B后,42例患者TBil、ALT水平均高于用药前( P=0.019;P=0.017),诊断为两性霉素B相关肝损伤者7例,肝损伤发生率为16.7%。Logistic回归分析结果显示,入院前3个月内肝损伤/肝病史是用药后γ-GT水平升高的独立危险因素( OR=2.029,95 %CI:1.037~3.970, P=0.039);多重线性回归分析结果显示,两性霉素B最大日剂量≥30 mg、累积剂量≥600 mg是用药后TBil水平升高的独立危险因素(标准化回归系数:0.59,95 %CI:0.28~0.90, P=0.001;标准化回归系数:1.61,95 %CI:0.14~3.07, P=0.033;R 2=0.524),入院前3个月内肝损伤/肝病史是用药后ALP和γ-GT升高的独立危险因素(标准化回归系数:0.85,95 %CI:0.25~1.45, P=0.006, R2=0.205;标准化系数:0.89,95 %CI:0.29~1.50, P=0.005, R2=0.206)。 结论:复旦大学附属中山医院两性霉素B致肝损伤的发生率为16.7%。两性霉素B最大日剂量≥30 mg、累积剂量≥600 mg是用药后TBil水平升高的独立危险因素,入院前3个月内肝损伤/肝病史是用药后ALP和γ-GT升高的独立危险因素。     

恶性血液病合并侵袭性真菌感染的临床分析

目的探讨和研究恶性血液病合并侵袭性真菌感染的治疗方案及临床分析。方法将84例于2006年11月～2011年11月期间在笔者所在医院治疗恶性血液合并侵袭性真菌感染的患者平均分为A组、B组及C组,每组28例患者。A组患者使用氟康唑进行治疗;B组患者使用伊曲康唑进行治疗;C组患者使用两性霉素B组进行治疗。对3组患者的临床疗效进行分析。结果氟康唑组治疗恶性血液病合并侵袭性真菌感染的有效率明显低于伊曲康唑组和两性霉素B组;伊曲康唑组和两性霉素B组并没在脂质体疗效上有显著的差异;两性霉素B组的不良反应率都要比伊曲康唑组和氟康唑组明显的高很多。结论使用伊曲康唑和两性霉素治疗恶性血液病合并侵袭性真菌感染的疗效十分显著,但与这两种药物相比较,氟康唑的安全性更佳。     

国产伏立康唑与两性霉素B治疗急性白血病合并侵袭性真菌感染的临床分析

目的:比较国产伏立康唑与两性霉素B治疗急性白血病合并侵袭性真菌感染的疗效及不良反应.方法:回顾性分析急性白血病合并侵袭性真菌感染患者27例临床资料,分为治疗组14例和对照组13例,治疗组静脉滴注伏立康唑4mg/kg,1次/12h,对照组静脉滴注两性霉素B从5mg开始逐渐增加剂量为1mg/kg,1次/d,两组均于用药2周后评价疗效及不良反应.结果:治疗组及对照组有效率分别为78.57%和46.15%,差异有统计学意义(P<0.05),不良反应发生率分别为28.57%、69.23%,治疗组明显低于对照组,差异有统计学意义(P<0.05).结论:国产伏立康唑治疗急性白血病合并侵袭性真菌感染较两性霉素B疗效好,不良反应少.     

成纤维细胞因子 23对急性肾损伤的诊断价值研究

目的探究成纤维细胞因子 23(FGF23)对急性肾损伤( AKI)的诊断价值。方法选取 2022年 2—7月山西医科大学第一医院重症医学科收治的 105例 AKI病人( AKI组)和 203例非 AKI病人(非 AKI组)为研究对象,检测两组病人的血浆 FGF23水平,并将 AKI组病人根据改善全球肾脏病预后组织( KDIGO)标准分期进行亚组分析;采用 Spearman相关性分析法分析 FGF23浓度与各指标间的相关性;采用多因素 logistic回归分析法分析 AKI的危险因素;绘制受试者操作特征曲线(ROC曲线),计算曲线下面积( AUC),探究血浆 FGF23水平对 AKI的诊断效能。结果两组病人在年龄、身体质量指数( BMI)方面均差异无统计学意义( P>0.05);与非 AKI组病人相比, AKI组的 ICU住院时间、总住院时间较高( P<0.001); AKI组病人在急性生理学和慢性健康状况评价 Ⅱ(APACHEⅡ)、血清肌酐、尿素、血浆 FGF23水平［27(20,32)分、 179(108.10,293.90)μmol/L、14.70(9.54,21.22)mmol/L、169.83(164.83,174.83)ng/L］等方面均高于非 AKI组［16(12,21)分、 61(48.10,77.80)μmol/L、5.53(4.03,8.05)mmol/L、139.83(124.83,156.50)ng/L］(P<0.001); AKI组的肾小球滤过率、尿量均低于非 AKI组( P<0.001); AKI不同分期血浆 FGF23水平随分期的递增而逐渐升高( P<0.05),且 1和 3期、 2和 3期组间比较差异有统计学意义( P<0.05); Scr浓度、 FGF23水平是 AKI的独立危险因素; FGF23用于诊断 AKI的灵敏度( 87.6%)高于 Scr,其特异度( 90.6%)与 Scr相差不大。结论 FGF23是 AKI的独立危险因素,对 AKI有较高的诊断价值。     

重症感染患者多黏菌素B相关急性肾损伤的发生情况及危险因素分析

目的探讨重症感染患者静脉使用多黏菌素B相关急性肾损伤(AKI)的发生情况和危险因素。方法收集2017年10月至2020年10月在中山大学附属第一医院住院期间静脉使用多黏菌素B治疗重症感染患者的电子病历进行回顾性分析, 筛选发生多黏菌素B相关AKI的患者, 统计分析AKI的发生时间、临床分期和转归, 计算多黏菌素B相关AKI发生率以及多黏菌素B用药第3、6、12和15天AKI的累积发生率。根据患者是否发生多黏菌素B相关AKI分为AKI组和非AKI组, 比较2组患者的临床特征, 应用多因素logistic回归方法分析AKI的危险因素, 计算比值比(OR)及其95%置信区间(CI)。结果纳入分析的患者共311例, 男性237例(76.2%), 女性74例(23.8%);中位年龄58(46, 70)岁;52例(16.7%)发生多黏菌素B相关AKI, AKI的发生时间为(4±2)d, 范围2～13 d;多黏菌素B用药第3、6、12和15天AKI的累积发生率(%)及其95%CI分别为9.1(3.0～19.4)、15.4(7.9～25.2)、21.5(12.8～31.6)和21.5(12.8～31....     

Nebulization of four commercially available amphotericin B formulations in persistently granulocytopenic rats with invasive pulmonary aspergillosis: evidence for long-term biological activity

The nebulization of amphotericin B desoxycholate (AMB-DOC), liposomal amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated aerosol droplets were measured. Pulmonary amphotericin B deposition and amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized amphotericin B formulations was evaluated in persistently granulocytopenic rats with invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals. Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC, L-AMB, ABLC and ABCD, respectively. Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations. Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for L-AMB only. All commercially available amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of invasive pulmonary aspergillosis.     

Retrospective investigation on the cases treated with liposomal amphotericin B

We have retrospectively investigated clinical profile, efficacy, and safety in 41 patients who were treated with liposomal amphotericin B (L-AMB) in Aichi Medical University Hospital between January 2008 and June 2009. It turned out that L-AMB was used for severe infectious diseases and 31.7% cases discontinued L-AMB therapy because of death. L-AMB was administered as the second-line therapy in 56.1% (23/41), and was not effective in 48.8% (20/41). L-AMB was administered as the first-line therapy in 43.9% (18/41); (1) 1 for cryptotoccal infection, (2) 7 for severe sepsis or septic shock, (3) 2 for the case which cannot remove medical device and might have biofilm formation, (4) 6 for the induction of step-down therapy concept, (5) 2 for febrile neutropenic patients who have needed aggressive empiric therapy. There was no significant difference in serum potassium level (p = 0.10) and serum creatinine level (p = 0.05) between pretreatment and posttreatment with L-AMB. The serum creatinine level before initial treatment with L-AMB was 1.31 +/- 1.30 mg/dL. The patients for 7.3% (3 cases) had dialyzed before initial treatment with L-AMB, however, there was no case who need dialysis after administration of L-AMB. As for the highest creatinine level in L-AMB administered cases, 29.3% (12/41) and 24.4% (10/41) were normal to abnormal, and abnormal to abnormal, respectively. This is the first investigational report when the serum creatinine level before initial administration of LAMB had been abnormal. The other antimicrobial agents, which might have influenced renal function, were administered to 51.2% cases (21/41). That means the cases administered L-AMB might have other bacterial infections. As for the serum creatinine level, we observed the changing cases and the cases which did not cause the change at all regardless of the administering period of LAMB. The serum potassium level before initial administration of L-AMB was 4.1 +/- 0.8 mEq/L, concomitant use of furosemide etc. was 31.7% (13/41), the lowest serum potassium level was 3.4 +/- 0.9 (1.9-6.2)mEq/L in during using L-AMB, the serum potassium was 34.1% (14/41) in replenish potassium during administration of L-AMB, and the total replenished potassium was 131.25 mEq. We did not observe the case who had died because of the low potassium. Since L-AMB was the only fungicidal drug, when we use L-AMB for the serious infectious diseases to make the best use of the characteristic, we have to pay attention to the concomitant medication, renal function and the serum potassium level.     

An Evaluation of Hepatotoxicity and Nephrotoxicity of Liposomal Amphotericin B (L-AMB)

Hepatic and renal functions are important considerations when selecting antifungal therapy. This investigation of liposomal amphotericin B (L-AMB) was conducted to determine the incidence and factors associated with the development of hepatotoxicity and nephrotoxicity. A retrospective chart review was conducted of 100 consecutive patients receiving L-AMB at doses of 1, 3, and 5 mg/kg. Hepatotoxicity was defined as an increase of bilirubin greater than 1.5 mg/dl or AST and ALT greater than three times the normal range. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or an increase of 50% from baseline. Patients were included if they were 18 years of age or older. Patients were excluded if they had developed hepatic or renal dysfunction prior to L-AMB administration. Seventy-five patients were included based upon the predefined inclusion/exclusion criteria. Twenty-one percent (16/75) developed hepatotoxicity based upon the predefined criteria. There were no additive correlates for this adverse effect. Overall, 56% (42/75) of patients developed nephrotoxicity. Seventy-four percent (31/42) were exposed to IV contrast, and 90% (38/42) were receiving nephrotoxins concurrently. Age, cumulative dose, concomitant nephrotoxins, and IV contrast exposure were associated with increased nephrotoxicity (p < 0.001). The development of hepatotoxicity was observed; however, no correlates (age, dose escalation, or cumulative dose) were significantly associated with its occurrence. Overall nephrotoxicity with L-AMB was common and often multifactorial. Lipid amphotericin B products are associated with lower rates of nephrotoxicity than conventional amphotericin; however, in this analysis, L-AMB was associated with a high incidence of nephrotoxicity.     

Retrospective analysis of the safety of four hours administration of liposomal amphotericin B in patients with chronic necrotizing pulmonary aspergillosis

We have retrospectively analyzed the safety of 4 hours administration of liposomal amphotericin B (L-AMB) compared to less than or equal to 3 hours administration in patients with chronic necrotizing pulmonary aspergillosis (CNPA). The elevation of serum creatinine in the group with 4 hours administration of L-AMB in patients with CNPA was equal to the group with shorter administration time (less than or equal to three hours). During the administration of L-AMB, the group with 4 hours administration of LAMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment than the group with shorter administration time. Additionally, white cell counts, platelet counts, serum creatinine, AST, ALT were not significantly different between L-AMB 4 hours administration group and less than or equal to 3 hours administration group. As the group with 4 hours administration of L-AMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment, this modality can be one of the safer ways in the treatment of CNPA. As L-AMB is one of the fungicidal agents, 4 hours administration of L-AMB can be an optimal way of treating CNPA.     

口服伏立康唑治疗的侵袭性肺部真菌感染高龄患者短期预后及影响因素分析

目的探讨口服伏立康唑治疗的侵袭性肺部真菌感染(IPFI)高龄患者短期预后状况及其影响因素。方法检索首都医科大学附属北京友谊医院信息系统,收集2016年1月至2017年12月在老年科住院、临床诊断为IPFI并口服伏立康唑治疗的高龄(≥80周岁)患者的电子病历,记录患者基本信息、基础疾病、合并用药、肝肾功能水平基线值、口服伏立康唑疗程以及用药后30 d内肝肾功能和生存状况,采用多因素Logistic回归方法分析患者口服伏立康唑后30 d内发生全因肝损伤、急性肾损伤(AKI)和死亡的影响因素,计算比值比(OR)及其95%置信区间(CI)。结果纳入分析的患者共34例,男性20例,女性14例;年龄(91±5)岁;口服伏立康唑后30 d内,发生肝损伤者6例(17.6%),发生AKI者7例(20.5%),死亡9例(26.5%)。多因素Logistic回归分析结果显示,年龄是口服伏立康唑后30 d内发生肝损伤的独立危险因素(OR=1.33,95%CI:1.03~1.73,P=0.03),基线估算肾小球滤过率(eGFR)<60ml/(min·1.73 m^2)是发生AKI的独立危险因素(OR=13.00,95%CI:1.27~133.29,P=0.03),AKI是30 d内死亡的独立危险因素(OR=48.00,95%CI:4.21~547.18,P<0.01)。结论高龄IPFI患者口服伏立康唑后30 d内发生肝损伤、AKI和死亡的风险较高,年龄、基线eGFR<60ml/(min·1.73 m^2)分别是发生肝损伤和AKI的独立危险因素,AKI是死亡的独立危险因素。     

Parenteral polymyxins: Assessing efficacy and safety in critically ill patients with renal dysfunction

Objectives:

Studies have established the effectiveness and safety of polymyxins in treating multidrug resistant (MDR) pathogens. However, the challenge is whether these nephrotoxic drugs can be administered in compromised renal states. The present study was undertaken to establish their role in such patients. The effectiveness and nephrotoxicity of polymyxins in critically ill-patients harboring MDR Gram-negative bacteria with already compromised renal functions was compared with those with normal renal functions.

Materials and Methods:

This retrospective cohort study (March 2008-March 2010) was conducted in the intensive care unit of a tertiary care hospital. A total of 48 eligible critically ill-patients receiving polymyxins were enrolled. A comparison was carried out (length of stay in hospital, mortality, renal function) between patients with acute kidney injury (AKI, n = 18; defined by the RIFLE classification) and patients with normal renal function (non-AKI, n = 30).

Results:

Patients with baseline AKI had a significantly higher adjusted mortality rate at admission when compared with the non-AKI group. At the end of therapy with polymyxins, 26.66% non-AKI patients developed renal dysfunction while 38.88% of patients in the AKI group had worsening of renal function (P = 0.006). However, there was no significant difference in the length of hospital stay (23.9 ± 13.24 vs. 30.5 ± 22.50; P = 0.406) and overall mortality (44.4% vs. 36.7%; P = 0.76) between two groups.

Conclusion:

Polymyxins can be administered in AKI patients with favorable results provided used judiciously with strict monitoring of renal functions, dose modification according to creatinine clearance and aggressive fluid management.KEY WORDS: Multidrug resistant Gram-negative septicemia, nephrotoxicity, polymyxin B, polymyxin E, renal dysfunction     

In vivo activity of liposomal amphotericin B against Exophiala dermatitidis in a murine lethal infection model

This study evaluated the in vivo activity of liposomal amphotericin B (L-AMB) and deoxycholate amphotericin B (D-AMB) in a murine model of disseminated infection caused by Exophiala dermatitidis. Cyclophosphamide-treated neutropenic ddY mice were inoculated intravenously with conidial suspensions of E. dermatitidis IFM 4827 or IFM 53409. The maximum tolerated doses of L-AMB and D-AMB were set at 10 mg/kg and 1 mg/kg, respectively. Four hours after infection, a single dose of L-AMB (0.3 to 10 mg/kg) or D-AMB (0.1 to 1 mg/kg) was administered intravenously. The efficacy of the antifungal treatment was assessed by the survival time over two weeks and the tissue fungal burdens 4 days after infection. L-AMB at a dose of > or =1 mg/kg significantly prolonged the survival time of mice infected with either strain compared with that of the control group. Percent survivals in the 10 mg/kg L-AMB-treated group (100% and 75%) were higher than those in the 1 mg/kg D-AMB-treated group (20% and 37.5%) in the IFM 4827 and IFM 53409 models, respectively. In the IFM 4827 model, 10 mg/kg L-AMB exhibited greater efficacy than 1 mg/kg D-AMB in terms of reducing the tissue fungal burdens (blood, lung, liver, spleen, and kidneys). These findings suggest that L-AMB was effective in the treatment of experimental disseminated E. dermatitidis infection, and the efficacy of L-AMB was superior to that of D-AMB.     

Natural products: potential treatments for cisplatin-induced nephrotoxicity

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%–35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.