伊曲康唑序贯治疗恶性血液病合并侵袭性真菌感染的疗效分析

目的分析伊曲康唑序贯治疗恶性血液病合并侵袭性真菌感染(IFI)的疗效及安全性。方法应用伊曲康唑序贯治疗47例恶性血液病合并IFI患者,观察其有效率、退热率、肺部影像学表现及毒副反应。结果伊曲康唑序贯治疗恶性血液病合并IFI的总有效率为61.7%,临床诊断、拟诊病例的有效率分别为64.3%、62.5%;其中发热患者35例,退热率77.1%;肺部CT表现阳性者43例,炎症较前吸收者占67.4%。毒副反应主要为低钾血症、肝损伤、黄疸、恶心、味觉异常、寒战。结论伊曲康唑序贯治疗恶性血液病合并IFI疗效确切,安全性好,可作为抢先治疗和经验治疗的选择。     

伊曲康唑注射液治疗恶性血液病侵袭性真菌感染的临床研究

目的研究伊曲康唑注射液治疗血液恶性病患者合并侵润性真菌感染的疗效。方法对30例按标准诊断患者应用伊曲康唑注射液,剂量200~400mg/d第1天,以后200mg/d用药14天。结果临床总有效率为66.7%,确诊病例、临床诊断病例与拟诊病例有效率分别为71.3%、86.3%、25.0%。确诊病例、临床诊断病例与拟诊病例有效率之间相比,有统计学差异(P<0.05);粒细胞减少,应用广谱抗生素及糖皮质激素是发病的主要危险因素;伊曲康唑注射液起效时间3天~7天,中位时间4天。结论伊曲康唑注射液对恶性血液病合并侵袭性真菌感染疗效显著,对存在危险因素的患者早期诊断,积极治疗,可取得良好效果。     

伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的疗效观察

目的评价伏立康唑和伊曲康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效和安全性。方法回顾性分析60例老年恶性肿瘤合并肺部真菌感染患者的临床资料,其中29例患者采用伏立康唑注射液治疗(伏立康唑组),31例患者采用伊曲康唑注射液治疗(伊曲康唑组),比较两种治疗方式的临床有效率和不良反应。结果伏立康唑组患者的有效率和不良反应率发生率分别为82.8%和13.8%,伊曲康唑组患者的有效率和不良反应发生率分别为70.9%和25.8%,两组患者比较,差异有统计学意义(P<0.05)。结论伏立康唑治疗老年恶性肿瘤合并肺部真菌感染的临床疗效优于伊曲康唑,安全性好,值得临床进一步推广。     

两种药物对儿童急性白血病合并真菌感染的临床疗效观察

目的探讨泊沙康唑和伊曲康唑预防及治疗儿童急性白血病合并侵袭性真菌感染的疗效。方法回顾性分析接受常规化疗的57例白血病患儿,分别应用口服伊曲康唑及泊沙康唑预防及治疗侵袭性真菌感染,分别对两组的不良反应及临床疗效进行比较。结果泊沙康唑组CR率和总有效率均高于伊曲康唑组,但差异无统计学意义(P>0.05);泊沙康唑组不良反应发生率较伊曲康唑组增高,差异无统计学意义(P>0.05),具体不良反应方面,泊沙康唑组肝功能损害发生率明显高于伊曲康唑组,差异有统计学意义(P<0.05),而在神经毒性、视觉障碍、肾功能损害及消化道反应方面,两组间差异无统计学意义(P>0.05)。结论泊沙康唑预防及治疗侵袭性真菌感染有效率高于伊曲康唑,其肝功能损害的不良反应同时也高于伊曲康唑。     

二性霉素B联用伊曲康唑经验性治疗血液病患儿并发肺部真菌感染22例

目的探讨血液病患儿并发肺部真菌感染的诊断和治疗。方法对22例采用二性霉素B和伊曲康唑治疗的血液病患儿的临床资料进行回顾性分析。结果22例中10例有呼吸道症状,17例胸部X线片检查可见大小不等的点片状阴影,3例胸部CT检查可见云絮状影;10例白色念珠菌感染,1例曲霉菌感染;6例（27．3％）中性粒细胞〈0．5×10^9／L,9例（40．9％）〈0．1×10^9／L;18例使用糖皮质激素（除外输注血液制品偶尔使用者）;所有真菌感染病例均采用广谱抗生素联合二性霉素B雾化吸人治疗5d以上;5d后症状无改善者加用伊曲康唑治疗2周以上;有效率为59．1％（13／22）,仅1例死亡。结论血液病患儿并发肺部真菌感染与强烈化疗、中性粒细胞减少、广谱抗生素的应用有关,早期诊断较困难。经验性二性霉素B和伊曲康唑治疗疗效确切,值得推广。     

老年恶性血液病患者并发侵袭性真菌感染的临床分析

 目的　探讨老年恶性血液病患者侵袭性真菌感染（IFI）的临床特点。方法　对2000 年 1 月至2007 年10月老年恶性血液病患者IFI的临床和实验室资料进行回顾性分析。结果　7 年间共诊断老年恶性血液病患者并发IFI 38 例。IFI发病与中性粒细胞缺乏症持续时间>5 d、广谱抗生素使用时间>7 d、合并糖尿病、住院天数>20 d、使用含激素的化疗方案等因素相关。IFI临床表现随感染部位的不同和感染真菌菌种不同而异,肺部是最常见的感染部位（25例,65.8 %）。菌种主要为白色念珠菌（14株,38.9 %）、曲霉菌（7株,19.4 %）。虽经两性霉素B和伊曲康唑等抗真菌药治疗,但仍有10例患者因难以控制的呼吸衰竭死亡。结论　老年恶性血液病患者IFI发病率高、预后差,发病与多种因素有关,应及早进行预防性治疗或早期经验性抗真菌治疗。     

伏立康唑注射液治疗血液肿瘤化疗后合并侵袭性肺部真菌感染的临床疗效

目的:分析伏立康唑注射液在血液肿瘤化疗后合并侵袭性肺部真菌感染（IPFI）经验性抗感染治疗的有效性和安全性。方法:回顾性分析2017年7月至2019年7月中国医学科学院肿瘤医院深圳医院合并IPFI的55例血液肿瘤患者应用伏立康唑注射液治疗的临床经验,其中男34例,女21例,中位年龄43.5岁（16～75岁）,观察患者应用伏立康唑注射液治疗后的临床疗效和不良反应。结果:本组55例患者诊断为IPFI感染,其中确诊6例、临床诊断24例、拟诊25例,全部患者均有典型的CT影像学表现,使用伏立康唑注射液治疗的中位时间是18.5天（7～56天）,应用伏立康唑注射液过程中有12例患者出现一过性幻觉,没有其它药物不良反应。最终全组患者有48例治愈、7例死亡,总有效率为87.3%。结论:伏立康唑注射液治疗IPFI疗效好,不良反应轻微,值得临床进一步应用。     

泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病的临床研究

目的 探讨泊沙康唑预防或挽救性治疗血液病患者侵袭性真菌病(IFD)的疗效及安全性.方法 回顾性分析2014年2月至2015年2月接受泊沙康唑预防或挽救性治疗IFD的25例血液病患者临床资料,患者平均年龄32.6岁(16～64岁).其中18例接受了泊沙康唑预防性治疗,7例接受了泊沙康唑挽救性治疗.结果 18例接受预防性治疗的患者在治疗期间或治疗结束后12周内,均没有出现IFD的临床表现(即无突破性真菌感染的病例),预防性治疗的平均疗程为21 d(14～35 d).7例接受挽救性治疗的患者均为伏立康唑治疗无效或不耐受者,挽救性治疗的总有效率为6/7,其中4例治愈,2例有效.所有患者中没有发现与泊沙康唑相关的明显不良反应.结论 泊沙康唑用于预防或挽救性治疗血液病患者IFD,均能够获得较好的临床疗效.     

伊曲康唑注射液治疗血液恶性肿瘤继发真菌感染的近期疗效和安全性观察

目的观察伊曲康唑注射液治疗血液恶性肿瘤患者继发真菌感染的近期疗效和安全性。方法选择60例临床诊断的血液恶性肿瘤继发真菌感染患者作为研究对象,随机分为观察组和对照组,每组30例,观察组患者给予常规对症治疗加伊曲康唑注射液,对照组患者给予常规对症治疗加两性霉素B治疗,疗程14d。观察两组患者近期疗效和不良反应情况。结果观察组和对照组患者总有效率分别为80.0%和53.3%,两组比较差异有统计学意义(P<0.05)。两组患者各项不良反应差异均无统计学意义(P>0.05);对照组患者不良反应发生率(66.7%)高于观察组(43.3%),但差异无统计学意义(P>0.05)。结论相对两性霉素B,应用伊曲康唑治疗血液恶性肿瘤继发真菌感染的近期疗效更好,推荐在临床上应用。不良反应有待于进一步研究。     

国产两性霉素B单药治疗恶性血液病合并侵袭性真菌感染的疗效观察

目的:探讨国产两性霉素B治疗恶性血液病患者合并侵袭性真菌的临床疗效及不良反应。方法:回顾性分析我院2008年-2011年确诊为恶性血液病合并侵袭性真菌感染(IFI)33例的临床表现和诊疗过程。结果:两性霉素B治疗IFI有效率73%,不良反应主要是发热,低血钾和肾功受损。结论:国产两性霉素B治疗血液病患者合并IFI疗效肯定,不良反应可以耐受,值得临床应用推广。     

伏立康唑一级预防急性白血病患者化疗期间并发真菌感染的临床疗效北大核心

目的:探讨初诊急性白血病患者化疗期间应用伏立康唑进行预防侵袭性真菌病(IFD)的临床疗效及安全性。方法:回顾性分析2016年02月至2018年03月期间我院血液科收治的初诊急性白血病行化疗的患者166例,按照是否使用抗真菌药进行预防性治疗分为观察组(应用伏立康唑进行预防治疗,n=103)和对照组(未应用抗真菌药物,n=63),比较两组患者IFD发生率差异,并分析抗真菌药物应用的不良反应。结果:观察组IFD发生率为10.7%,对照组为33.3%,两组患者的IFD发生率有明显差异(P<0.05);所有应用伏立康唑进行预防治疗的患者均未出现严重的不良反应。结论:伏立康唑可以有效减低急性白血病患者化疗期间IFD发生率,并且有着较好的安全性,值得在临床推广应用。     

Isavuconazole for treatment of invasive fungal diseases caused by more than one fungal species

The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown. We documented the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species. VITAL was a single‐arm, international, open‐label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs. The primary outcome was the overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by multiple fungal species. Fifteen patients were included in this analysis (including Aspergillus spp., n = 11; without Aspergillus spp., n = 4); median treatment duration was 97 days [range, 6‐544] days). Overall treatment success was observed in 2/15 patients (13.3%) at Days 42 and 84, and 2/14 (14.3%) at EOT. All‐cause mortality was 2/15 (13.3%) at Day 42 and 4/15 (26.7%) at Day 84. All patients had ≥1 treatment‐emergent adverse event (TEAE); 12 patients (80.0%) had serious TEAEs; TEAEs led to discontinuation of isavuconazole in two patients (13.3%). Isavuconazole may be useful to treat some IFDs caused by multiple fungal species.     

Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients.

PURPOSE: Efficacy of antifungal prophylaxis has not yet been convincingly proven in numerous trials of various antifungals. New evidence and the anti-Aspergillus efficacy of itraconazole prompted a new look at the data for the prevention of invasive fungal infections. PATIENTS AND METHODS: Randomized, controlled studies with itraconazole for antifungal prophylaxis in neutropenic patients with hematologic malignancies were identified from electronic databases and hand searching. RESULTS: Thirteen randomized trials included 3,597 patients who were assessable for invasive fungal infections. Itraconazole reduced the incidence of invasive fungal infection (mean relative risk reduction, 40% +/- 13%; P =.002), the incidence of invasive yeast infections (mean, 53% +/- 19%; P =.004) and the mortality from invasive fungal infections (mean, 35% +/- 17%; P =.04) significantly. The incidence of invasive Aspergillus infections was only reduced in trials using the itraconazole cyclodextrine solution (mean, 48% +/- 21%; P =.02) and not itraconazole capsules (mean, 75% +/- 73% increase; P =.3). The overall mortality was not changed. Adverse effects were rare, hypokalemia was noted in three studies, and a higher rate of drug discontinuation was found in trials that compared itraconazole cyclodextrine solution to a control without cyclodextrine. The effect of prophylaxis was clearly associated with a higher bioavailable dose of itraconazole. CONCLUSION: Antifungal prophylaxis with itraconazole effectively prevents proven invasive fungal infections and-shown for the first time for antifungal prophylaxis-reduces mortality from these infections and the rate of invasive Aspergillus infections in neutropenic patients with hematologic malignancies. Adequate doses of the oral cyclodextrine solution (at least 400 mg/d) or i.v. formulations (200 mg/d) of itraconazole are necessary for these effects.     

血液系统恶性肿瘤患者侵袭性真菌感染的诊断与治疗进展

血液系统恶性肿瘤患者中侵袭性真菌病（invasive fungal disease,IFD）的发病率和死亡率均较高,早期诊断和治疗可以有效降低IFD的发生率。目前间接试验方法（包括放射方法）均无法明确诊断侵袭性真菌感染（invasive fungal infection,IFI）,需结合不同的诊断方法及患者的临床表现综合判断。但即使未得到明确的IFD诊断证据,对符合条件的患者仍需进行早期干预治疗。临床治疗方案的选择需综合考虑患者临床特征、实验室和放射学检查结果、药物药理学特性和患者经济负担等因素的影响。本文拟对血液系统恶性肿瘤患者IFI的诊断与治疗进展进行综述。      

Safety and efficacy of itraconazole compared to amphotericin B as empirical antifungal therapy for neutropenic fever in patients with haematological malignancy

BACKGROUND: Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients. PATIENTS AND METHODS: In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups. RESULTS: Significantly fewer itraconazole patients discontinued treatment due to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001). The main reason for discontinuation was a rise in serum creatinine (1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability. CONCLUSIONS: Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients.     

泊沙康唑预防性抗真菌治疗在血液系统恶性肿瘤患者中的应用

目的 研究血液系统恶性肿瘤患者中预防性使用泊沙康唑抗真菌治疗的有效性和安全性.方法 回顾性分析2014年2月至2017年4月上海瑞金医院102例血液系统恶性肿瘤患者化疗期间预防性使用泊沙康唑抗真菌治疗的效果,采用Spearman进行相关性分析.结果 102例血液系统恶性肿瘤患者化疗期间,给予泊沙康唑预防性治疗后,2例(1.96%)发生侵袭性真菌感染.2例患者治疗期间发生死亡,但与泊沙康唑治疗无关.11例患者因不良反应停用泊沙康唑,不良反应导致的停药率为10.8%;2例侵袭性真菌感染抗真菌治疗失败和1例未确诊侵袭性真菌病患者停用泊沙康唑,泊沙康唑整体停药率为13.7%(14/102).泊沙康唑使用时间与住院时间、中性粒细胞缺乏时间均无相关性(rs=-0.02,P=0.853;rs=0.167,P=0.113),住院时间与中性粒细胞缺乏时间呈正相关(rs=0.448,P=0.000).结论 泊沙康唑用于血液系统恶性肿瘤患者侵袭性真菌病的预防性治疗,有效性和安全性均较佳.     

Posaconazole prophylaxis – impact on incidence of invasive fungal disease and antifungal treatment in haematological patients

Since two large‐scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real‐life setting. We analysed retrospectively incidence and severity of IFD in high‐risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non‐prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high‐risk patients.