氟康唑治疗恶性血液病的真菌感染

研究了采用氟康唑治疗联合化疗后ＡＬ，ＮＨＬ共３１例真菌感染患者的效果，以制霉菌素，咪康唑和酮康唑等治疗的２４例作为对照组。观察结果表明：大肤康治疗组的有效率明显高于对照组和制霉菌素治疗组。     

氟康唑治疗恶性血液病的真菌感染

研究了采用氟康唑（大扶康Ｄｉｆｌｕｃａｎ）治疗联合化疗后ＡＬ、ＮＨＬ共３１例真菌感染患者的效果，以制霉菌素、咪康唑和酮康唑等治疗的２４例作为对照组。观察结果表明：大扶康治疗组的有效率明显高于对黑组和制霉菌素治疗组。本组中白色念珠菌感染的病例经氟康唑治疗全部有效。大扶康治疗无效的４例中有２例不能排除疗程不足因素的影响，有１例经尸捡证实为严重的全身性多脏器曲霉菌感染。结合文献，作者认为氟度唑与其它唑类药物有共同的缺陷，即治疗曲、毛霉菌效果差。本组观察还提示，大扶康毒副作用小，患者易耐受。     

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。     

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。     

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     

血清半乳甘露聚糖检测诊断恶性血液病患者侵袭性真菌感染的临床意义

 目的　探讨血清半乳甘露聚糖（GM）检测作为侵袭性真菌感染（IFI）快速检测方法的可行性及其对恶性血液病患者早期诊断的意义。方法　选取体温≥38 ℃持续96 h以上,经合理广谱抗生素治疗无效或起初治疗有效但随后体温再次升高,1周内未用过抗真菌药物的恶性血液肿瘤患者39例为研究对象。每周进行2次血清GM检测,连续监测3周。用统计学方法计算GM在IFI早期诊断中的敏感度、特异度等指标,与传统的诊断方法进行比较,并观察其与IFI预后间的关系。结果　39例入组患者中,31例临床诊断IFI,GM实验的阳性率为80.6 %（界值为0.5）,敏感度为87.1 %,特异度62.5 %,阳性预测值（PV+）90 %,阴性预测值（PV-）55.6 %（κ＝0.474）。8例排除IFI诊断中,GM阳性3例。首次血清GM阳性结果出现于临床诊断前24 d至临床诊断后3 d,平均出现于临床诊断前（2.8±4.8）d;抗真菌治疗过程中,感染恶化患者血清GM水平持续升高,治疗好转患者明显下降。结论　作为IFI诊断方法,GM实验结果与临床IFI诊断具有很好的一致性;与传统培养方法相比,具有早期、快速、敏感性和特异性较高的优点。     

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。     

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。     

恶性血液病合并粒细胞缺乏患者并发深部真菌感染的研究

目的：研究恶性血液病合并粒细胞缺乏患者并发深部真菌感染的临床特点。方法：回顾性分析30例粒细胞缺乏合并DFI患者的资料。结果：接受骨髓移植、多次化疗、反复应用激素及免疫抑制剂等治疗的粒细胞缺乏患者,细胞及体液免疫功能明显降低,同时长期应用广谱抗生素破坏了宿主正常菌群生态平衡,成为真菌感染的高危人群。医院内DFI的病原菌主要为白色念珠菌,占61.8%;应用rhG-CSF等药物能缩短粒缺的时间,有利于DFI的治疗。结论：粒细胞缺乏的血液病患者极易并发深部真菌感染,应尽早行保护性隔离。应及时应用rhG-CSF,缩短白细胞减少持续时间,合理使用抗生素,对高度怀疑真菌感染病灶存在时应预防性应用抗真菌治疗,适时据培养结果选用有效抗菌药物。     

Our 2014 approach to breakthrough invasive fungal infections

Evidence‐based clinical pathways to direct antifungal treatment options in patients with breakthrough fungal infections during current systemic antifungal therapy are not available. Nonetheless, for defined settings of such breakthrough infections approaches to management can be recommended based on clinical, epidemiological, pharmacological and in vitro susceptibility data.     

恶性肿瘤患者侵袭性真菌感染危险因素分析

目的:研究肿瘤患者侵袭性真菌感染的危险因素和菌株分布等,为预防与治疗肿瘤患者侵袭性真菌感染提供参考依据。方法:回顾性分析2012年3月-2014年3月96例侵袭性真菌感染的肿瘤患者。96例侵袭性真菌感染的患者主要类型为肺癌32例,肝癌12例,胃癌18例,食道癌7例,胰腺癌9例,肠癌4例,白血病8例,卵巢癌3例,鼻咽癌1例,前列腺癌2例。分析研究侵袭性真菌感染的病原菌分布、高危影响因素以及与肿瘤转移的关系等。结果:住院时间长短、肿瘤早晚期、抗肿瘤药物的使用和侵袭性操作等与肿瘤患者侵袭性真菌感染有明显相关性,差异有统计学意义。侵袭性真菌感染的标本分别为痰、尿、血液、腹水、胸水,胆汁和脑脊液,各部位主要感染的侵袭性真菌为白色念珠菌,占54.8%。96例患者共20例死亡,侵袭性真菌感染的相关死亡率为20.8%,其中有45例患者发生了远处肿瘤转移,肿瘤转移患者侵袭性真菌感染在血标本中更易检出。结论:肿瘤患者放化疗后, 具有较高的侵袭性真菌感染率,并且真菌感染多发生于肿瘤转移患者。     

Posaconazole in intensive care patients I: invasive fungal infections in surgical intensive care and case presentation

Critically ill patients after extended surgical procedures are at high risk for postoperative infections. Fungal infections play a substantial role for immunocompromised patients, e.g. after solid organ transplantation or under chronic corticoid therapy. Posaconazole, a new broad-spectrum triazole effective against Aspergillus and Candida species as well as many fungi that are resistant to other antifungals, is well tolerated and can be used as an alternative in salvage therapy. Posaconazole can be administered via gavage so that antifungal therapy can be switched from an expensive intravenously applied antifungal to oral posaconazole at an early stage. Two case reports are presented, which show that posaconazole was efficacious and well tolerated following antifungal therapy with another azole. It was administered without difficulty via gavage to a patient receiving artificial respiration and dialysis.     

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI‐associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost‐effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision‐analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost‐effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost‐effective than posaconazole regarding cost per additional IFI and additional death avoided.     

Diagnosis of invasive fungal infections using real-time PCR assay in paediatric acute leukaemia induction

Invasive fungal infections (IFI) lead to morbidity and mortality in neutropenic patients and in allogenic stem cell transplantation. Serum-based fungal detection assays have limitation of specificity or sensitivity. Studies on fungal DNA detection using real-time PCR in childhood leukaemia are lacking. The aim of this study was to develop sensitive and specific diagnostic tools for IFI in paediatric acute leukaemia patients using real-time PCR. Of 100 randomised paediatric acute leukaemia patients receiving antifungal prophylaxis with voriconazole/amphotericin B, single peripheral whole blood sample in EDTA was used for Pan-AC real-time PCR assay (detects nine Candida and six Aspergillus species) in patients who failed prophylaxis due to proven, probable, possible or suspected fungal infections. PCR results were retrospectively correlated with clinical profile. Real-time PCR test was positive in 18/29 (62%) patients who failed prophylaxis. The only patient with proven IFI (mucormycosis), real-time PCR assay was negative. Real-time PCR was positive in 2/4 (50%) patients with possible and 16/24 (66.6%) suspected IFI and 5/10 (50%) patients with pneumonia. By applying method A/B, sensitivity and positive predictive value could not be commented due to unproven Aspergillus or Candida infections; specificity and negative predictive values (NPV) were 41% and 100% respectively; by method C (included episodes of possible IFI as true positive), sensitivity, specificity, PPV and NPV were 50%, 36%, 11% and 81% respectively. In those with suspected IFI, 8/24 (33.3%) were PCR negative and unnecessarily received empirical antifungal therapy (EAFT). Real-time PCR is a practical, rapid, non-invasive screening test for excluding IFI in paediatric leukaemia. The high NPV makes real-time PCR a promising tool to use this prior to initiating EAFT in antibiotic-resistant febrile neutropenic patients; this would avoid toxicity, cost and hospitalisation for EAFT (ClinicalTrials.gov identifier:NCT00624143).     

Haemopoietic progenitor cell transplantation in patients with previous history of invasive fungal infection

The aim of this retrospective study conducted between H.U.Marques de Valdecilla (Spain) and the Royal Marsden NHS Trust (UK) was to analyse the outcome of patients who underwent haemopoietic progenitor cell transplantation (HPCT) after a previous history of Invasive fungal infections (IFI). This study includes 27 patients (15 autologous, 12 allogeneic). The diagnosis of IFI was microbiologically proven in 21 cases and only radiologically in six. Pre-HPCT treatment included intravenous antifungals in all and surgical excision in eight cases. All patients received post-HPCT antifungal prophylaxis. Median time from diagnosis of IFI to HPCT was 131 days. At median follow-up of 193 days, three patients (two allogeneic, one autologous) had relapse of IFI resulting in death in all cases. One of them had received TBI and two were receiving treatment for graft versus host disease. Each patient was receiving a different form of prophylaxis. Overall, seven patients are alive and disease-free. Ten patients died from disease progression and 10 from transplant-related toxicity, including IFI. In our experience, the risk of post-HPCT reactivation of a previous IFI is low (11%), so IFI should not be an absolute contraindication for HPCT. The combination of aggressive antifungal treatment for IFI and antifungal prophylaxis throughout HPCT reduces the probability of reactivation.     

米卡芬净治疗小儿白血病粒缺期肺侵袭性真菌感染的临床观察

目的:分析、评价米卡芬净治疗小儿白血病粒缺期肺侵袭性真菌感染的临床疗效及安全性。方法:选择2007年1月-2010年7月本院儿科血液病房诊治的小儿白血病并发肺侵袭性真菌感染患儿34例,应用米卡芬净进行治疗,剂量为3-5mg/(kg.d),一次静脉输注,7天为1个疗程,治疗1-4疗程,同时动态监测G试验、肺高分辨CT及各脏器功能指标。结果:痊愈16例,显效6例,进步5例,无效7例,总有效率为64.7%。死亡8例,病死率为23.5%。本组患儿未发现不良反应。结论:加强早期诊断,尤其动态监测G试验及高分辨肺CT及早进行拟诊肺侵袭性真菌感染是治疗成功的关键,米卡芬净在小儿白血病粒缺期肺侵袭性真菌感染治疗中显示了安全、有效的抗真菌作用。     

米卡芬净治疗小儿白血病粒缺期肺侵袭性真菌感染的临床观察

目的：分析、评价米卡芬净治疗小儿白血病粒缺期肺侵袭性真菌感染的临床疗效及安全性。方法：选择2007年1月-2010年7月本院儿科血液病房诊治的小儿白血病并发肺侵袭性真菌感染患儿34例,应用米卡芬净进行治疗,剂量为3-5mg/（kg.d）,一次静脉输注,7天为1个疗程,治疗1-4疗程,同时动态监测G试验、肺高分辨CT及各脏器功能指标。结果：痊愈16例,显效6例,进步5例,无效7例,总有效率为64.7%。死亡8例,病死率为23.5%。本组患儿未发现不良反应。结论：加强早期诊断,尤其动态监测G试验及高分辨肺CT及早进行拟诊肺侵袭性真菌感染是治疗成功的关键,米卡芬净在小儿白血病粒缺期肺侵袭性真菌感染治疗中显示了安全、有效的抗真菌作用。