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。     

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。     

伊曲康唑注射液治疗血液病合并侵袭性真菌病临床分析

目的：探讨伊曲康唑注射液对血液病患者合并侵袭性真菌病分层治疗的疗效及安全性。方法回顾性分析160例血液病合并侵袭性真菌病患者接受伊曲康唑注射液分层治疗的疗效和安全性,并对相关影响因素进行回顾性分析。结果伊曲康唑对全部患者的总有效率为58.12%（93／160）,其中经验治疗、诊断驱动治疗和目标治疗的有效率分别为65.82%（52／160）、53.57%（30／160）、44.00%（11／160）,三组间的疗效差异无统计学意义（P＝0.054）。相关不良事件发生率为8.13%（13／160）,主要为肝功能损害。多因素分析显示伊曲康唑注射液治疗侵袭性真菌病的疗效不受年龄、真菌感染病史、是否存在粒细胞缺乏、是否初治等因素的影响。结论伊曲康唑注射液对血液病患者合并侵袭性真菌病的各个分层治疗均有良好的疗效,且安全可靠。     

伊曲康唑与两性霉素B治疗恶性实体瘤化疗后真菌感染的临床对照研究

目的:比较伊曲康唑与两性霉素B治疗恶性实体瘤化疗后真菌感染的疗效和毒副作用。方法:30例恶性实体瘤化疗后真菌感染患者,包括自体造血干细胞移植13例,常规强化治疗17例。按时间先后分为两组,1996年6月~2003年11月真菌感染15例患者均用两性霉素B治疗,2003年12月~2005年10月真菌感染15例患者均用伊曲康唑治疗。观察并评价两药疗效和毒副作用。结果:伊曲康唑和两性霉素B治疗恶性实体瘤中性粒细胞减少真菌感染疗效分别为86.8%和93.4%,两组比较无统计学意义(P=0.482);两性霉素B组出现发热、寒战33.3%、低血钾39.6%,伊曲康唑组均未出现以上不良反应,两组对比有统计学意义(P<0.05)。结论:两药治疗真菌感染疗效相似,但伊曲康唑的毒副作用轻。     

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。     

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。     

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。     

恶性血液病并发呼吸道真菌感染68例诊治分析

目的 探讨恶性血液病化疗后并发呼吸道真菌感染的原因、诊治及预防。方法 对６８例合并呼吸道真菌感洒患者观察临床症状、体征、通过痰培养确诊，分析其原因。并以酮康唑、伊曲康唑、氟康唑治疗，比较疗效。结果 ６８例患者中合并念珠菌感染５８例，曲菌２例，毛霉菌８例，经用抗真菌药物治疗后，酮康唑组治愈率３８．５％，伊曲康唑组８８．９％，氟康唑组９７．３％。结论对呼吸道真菌染应注意早期预防、早期诊断、选用高效低毒     

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。     

氟康唑治疗恶性血液病化疗后真菌感染21例

目的观察氟康唑治疗恶性血液病化疗后合并真菌感染的疗效。方法对1998年7月至2006年6月收治的21例恶性血液病化疗后合并真菌感染的患者作回顾性分析。结果总有效率为76．19％（16／21）,确诊病例为71．43％（5／7）,临床诊断病例为90．91％（10／11）,拟诊病例66．66％（2／3）。结论氟康唑对恶性血液病化疗后合并真菌感染的患者疗效确切,价格较低,可作为一线治疗推荐药物。     

G试验联合GM试验在恶性血液病侵袭性真菌感染的诊断价值

目的：探讨血浆1,3-β-D葡聚糖检测（G实验）联合曲霉半乳甘露聚糖检测（GM试验）对恶性血液病侵袭性真菌感染（IFI）的诊断价值。方法：应用MB-80微生物动态快速检测系统和酶联免疫吸附法定量检测血浆1,3-β-D葡聚糖及半乳甘露聚糖的含量,将检测结果及临床特征进行分析。按照欧洲癌症研究治疗组织及真菌研究组（EORTC/MSG）诊断标准,在349例患者中,确定诊断2例,临床诊断23例,临床拟诊175例,排除诊断149例。结果：G、GM试验分别以20ng/ml、0.5为诊断界值,G试验的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）分别为77%、89.9%、91.1%、74.4%。G/GM试验的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）分别为100%、90.4%、85.9%、100%。结论：G试验联合GM试验是诊断恶性血液病患者IFI的早期、快速的方法。     

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。     

Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic‐driven approach and itraconazole oral solution

Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic‐driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non‐significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic‐driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non‐statistically significant, number of IFI in our medical centre.     

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.     

Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole.

This study analyses invasive fungal infections in neutropenic patients with haematological malignancies during antifungal prophylaxis with itraconazole. From September 1994 to December 1998 20 patients developed fungal infections. Two patients suffered from disseminated infections by yeasts and 18 patients suffered from pulmonary infections by moulds (eight proven, 10 highly probable in high-resolution CT scans). In these patients the itraconazole trough concentrations exceeded 500 ng ml-1 (measured by high performance liquid chromatography) significantly less often (median 48%, interquartile range 0-100%) than in another group of 150 leukaemia patients without invasive fungal infections who received 287 courses of prophylaxis with itraconazole at our institution (median 100%, interquartile range 38-100%, P = 0.039). Twelve patients died, six of these had refractory disease. Patients with fatal invasive fungal infections had lower median itraconazole concentrations immediately before occurrence of the infection than patients with non-fatal infections: 120 (0-478) ng ml-1 versus 690 (305-1908) ng ml-1 (P = 0.039). In conclusion, this analysis of breakthrough invasive fungal infections during prophylaxis with itraconazole demonstrates that patients with itraconazole trough concentrations below 500 ng ml-1 were significantly more likely to develop fungal infections and that the last itraconazole trough concentration before occurrence of the infection was significantly lower in patients with fatal invasive fungal infections.     

Invasive fungal infections are responsible for one-fifth of the infectious deaths in children with ALL

The following report will discuss in detail all lethal invasive fungal infections (IFI) that occurred in a group of 2021 children with acute lymphoblasic leukaemia (ALL). The German ALL-Berlin-Frankfurt-Muenster (BFM) study group is one of the largest cooperation for the treatment of childhood ALL. Between 1995 and 2000, 2021 children with ALL received chemotherapy according to the German BFM 95 protocols (ALL-BFM 95). This population was retrospectively screened, whether a lethal fungal infection occurred: totally, in this group, 43 of 2021 (2.1%) children died because of infections. Nine of 43 (21%) patients died in the context of an IFI: six fatal Aspergillus infections and three fatal yeast infections were reported. The following report will focus on the nine children with ALL who died from IFI. The underlying risk factors (RF) included neutropenia (seven of nine patients) and steroid medication (nine of nine patients). Seven of nine children had additional medical complications (e.g. liver failure, haemolytic uraemic syndrome and acute renal failure). In six of nine children the fungal infection was progressive despite intravenous antimycotic therapy, three patients received no antifungal therapy, as IFI was not considered. The progression of IFI despite antimycotic therapy illustrates the inherent problems of diagnosis and the need for innovative therapeutic modalities. The high percentage (21%) of death from IFI among lethal infections in paediatric ALL patients illustrates the relevance of fungi in this group of patients. On the contrary, the total number of IFI in paediatric ALL patients remains to be determined, as only lethal infections were included in this report.     

Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial.

BACKGROUND: We performed a prospective, randomized, open-label trial to evaluate the efficacy of low-dose liposomal amphotericin B (L-AmB) to reduce the incidence of invasive fungal infections (IFI) in patients with hematological malignancies and prolonged neutropenia (>10 days) following intensive chemotherapy. PATIENTS AND METHODS: In 219 neutropenic episodes (NE) of 132 patients randomization was performed. Patients received either 50 mg L-AmB every other day (arm A) or no systemic antifungal prophylaxis (arm B). RESULTS: In the first NE of each patient the incidence of proven or probable IFI (primary end point) was five of 75 patients (6.7%) in arm A and 20 of 57 patients (35%) in arm B (P=0.001). Invasive aspergillosis occurred less frequently in patients receiving L-AmB-prophylaxis (P=0.0057), whereas the reduction of invasive candidiasis did not reach statistical significance (P=0.0655). In all NE the incidence of IFI was five of 110 NE (4.6%) in arm A versus 22 of 109 NE (20.2%) in arm B (P<0.01). Adverse events, possibly related to L-AmB, were observed in five NE (4.6%) and L-AmB was discontinued in three NE (2.8%). No grade 3 or 4 toxicities were observed. CONCLUSIONS: Antifungal prophylaxis with low-dose L-AmB proved to be feasible and effective in our trial.     

Prophylaxis of Fungal Infections with Itraconazole during Remission-Induction Therapy

Summary: Deep fungal infections are an increasing problem in the treatment of acute leukemias and malignant lympho-mas. Risk factors are known but unavoidable. Because of diagnostic difficulties most patients are treated empirically with intravenous amphotericin B. This drug's toxicity increases morbidity and mortality. An orally absorbable triazole derivative, itraconazole, may offer effective and safe prophylaxis against deep candidosis and aspergillosis in these patients.
Such infections have been treated successfully with oral itraconazole even when resistant to intravenous amphotericin B. In retrospective comparative studies there are significantly less deep fungal infections in patients given itraconazole. The significance of the difference varies between studies. Pharmaco-kinetic data confirm therapeutic plasma levels of itraconazole but with wide variation within and between patients.
The current large, multi-centre, randomised, double-blind, prospective trial of oral itraconazole versus placebo in the U.K. will test its prophylactic efficacy against deep fungal infections during treatment of haematological malignancies.     

Prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in neutropenic patients with hematological malignancies: a meta-analysis of randomized-controlled trials

Antifungal prophylaxis using fluconazole or itraconazole has been studied for many years but still no consensus has been reached regarding their safety and effectiveness. We performed a systematic meta-analysis to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematological malignancies. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane-controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 1/2009) searches. Risk ratio (RR) and 95% confidence intervals (CIs) were calculated using the random effect model. Nine RCTs were identified that were published in full text. Significantly, fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (RR 0.45, 95% CI 0.27–0.75, P = 0.002). There were statistically significant differences regarding fungal infections (RR 1.34, 95% CI 1.08–1.67, P = 0.009) and invasive fungal infections (RR 1.33, 95% CI 1.02–1.73, P = 0.03) between the two educations. There were no statistically significant differences regarding overall mortality (RR 0.95, 95% CI 0.77–1.17, P = 0.64), fungal-related mortality (RR 1.28, 95% CI 0.80–2.07, P = 0.31), and proven fungal infections (RR 1.38, 95% CI 0.75–2.53, P = 0.30). The analysis of published evidence reveals that itraconazole administration resulted in significantly fewer episodes of fungal infections and invasive fungal infections compared with fluconazole.