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。     

卡泊芬净治疗47例恶性血液病患者侵袭性真菌感染

 目的　评价卡泊芬净治疗恶性血液病合并侵袭性真菌感染（IFI）的疗效与安全性。方法　采用回顾性分析法统计山西医科大学第二医院2007年8月至2009年9月47例恶性血液病住院患者的临床资料,其中男28例,女19例,中位年龄42（17～76）岁。47例患者中急性髓细胞白血病（AML）28例、急性淋巴细胞白血病（ALL）11例、重型再生障碍性贫血（SAA）2例、骨髓增生异常综合征（MDS）3例、非霍奇金淋巴瘤（NHL）自体造血干细胞移植术后1例、慢性粒细胞白血病（CML）异基因造血干细胞移植术后2例,所有恶性血液病患者处于化疗后骨髓抑制期或造血干细胞移植术后,使用卡泊芬净的疗效和不良事件（卡泊芬净首日70 mg／d,之后50 mg／d静脉输注,输注时间不得少于1 h,疗程依患者病情而定）。结果　47例病例分析中显示卡泊芬净总有效例数为25例（58.1 %）,药物相关的不良反应发生率低且较轻。结论　卡泊芬净抗菌谱广,疗效确切,安全性好,是血液病患者抗真菌经验治疗的较为理想的药物。     

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。     

恶性血液病合并带状疱疹的临床分析

目的探讨恶性血液病患者治疗过程中合并带状疱疹的发病情况、危险因素、治疗及预后。方法回顾性分析21例合并带状疱疹的恶性血液病患者的临床资料。结果 741例恶性血液病患者中有21例合并带状疱疹,发生率为2.8%。感染发生部位多位于胸、腰部皮肤。中位发病时间为化疗开始后4.5个月。年龄≥45岁的患者带状疱疹发生率明显高于<45岁患者(3.9%vs 0.8%,P=0.01)。采用含利妥昔单抗化疗方案的患者带状疱疹发生率显著高于不含利妥昔单抗化疗方案的患者(7.0%vs 2.3%,P=0.026)。治疗以静脉滴注阿昔洛韦或阿糖腺苷为主要方案,平均病程为12 d,2例高龄患者同时合并真菌感染死亡,其余患者均治愈。结论恶性血液病患者合并带状疱疹的发生率较正常人群明显增高;年龄≥45岁、应用利妥昔单抗可能是其发生的危险因素;通过有效抗病毒治疗,可使大部分患者获得痊愈;对于免疫力异常低下患者,合并带状疱疹提示预后不良。     

恶性血液病患者医院感染135例临床分析

目的探讨恶性血液病患者医院感染的发病率、易感因素、感染的好发部位、病原微生物分布及药敏情况.方法对我科2003年1月至2004年12月间住院的恶性血液病患者发生院内感染135例次进行统计分析.结果 356例次恶性血液病患者住院过程中各种医院感染发生率37.9%;易感因素与年龄、原发疾病类型、粒细胞缺乏、化疗药物及免疫抑制剂的使用等因素有关;感染的好发部位以呼吸道感染最为常见,其次为血液、胃肠道;病原菌以革兰氏阴性杆菌和念珠菌为主;药敏试验表明所有革兰氏阴性杆菌均对多种抗生素均有不同程度的耐药,而对亚胺培南及头孢他啶耐药率相对较少,未检出耐舒谱深的菌株.结论恶性血液病患者免疫力低下,医院感染的发生率较高,尤其对老年人和粒细胞缺乏者,应加强治疗过程的环境保护,及时使用恰当的支持治疗,对重度感染者应尽早使用广谱高效抗生素治疗.     

恶性血液病医院相关感染及病原菌分析

 目的　了解恶性血液病院内相关感染的高发因素及病原菌分布。方法　对山西省肿瘤医院血液科2006年1月至2008年12月住院患者中发生院内感染的499例恶性血液病患者进行回顾性调查,并对感染部位、药敏菌株进行分析。结果　恶性血液病患者3年的院内感染发生率为11.83 %。感染部位前3位的是上呼吸道、下呼吸道、其他（以口腔、生殖道为主）,部位构成比分别为45.29 %、25.05 %、8.22 %。病原菌前5位依次为白色念珠菌、肺炎克雷伯菌、阴沟肠杆菌、大肠埃希菌、D群链球菌。结论　恶性血液病患者免疫功能低下,放、化疗导致患者中性粒细胞减少或缺乏、细胞免疫功能受损是院内感染的主要原因。要重视院内感染的细菌检测及药敏试验,从而及时、准确应用敏感的抗菌药物,减少耐药菌的产生。     

伏立康唑治疗血液病患者侵袭性真菌感染26例疗效观察

侵袭性真菌感染(IFI)是血液系统疾病尤其是恶性血液病治疗过程中常见的并发症。近年来,由于大剂量化疗药物以及免疫抑制广泛应用,血液病患者侵袭性真菌感染(inva-sivefungal infection,IFI)罹患率逐渐增高。而IFI目前诊断手段匮乏,病情进展迅速,病死率高,且传统抗真菌药物不良反     

异基因造血干细胞移植治疗恶性血液病的预后分析

 目的　探讨异基因造血干细胞移植（allo-HSCT）治疗恶性血液病的预后相关因素。方法　1997年7月至2008年8月,对26例血液病患者行allo-HSCT,其中急性白血病（AL）14例,慢性髓系白血病（CML）10例,骨髓增生异常综合征（MDS）2例;移植供受体22例为同胞HLA全相合,4例为同胞HLA不全相合。结果　所有患者达到稳定的供者植入,随访至今,累积总生存（OS）率为63.9 %,累积无病生存（DFS）率为62.6 %;15例（57.7 %）发生移植物抗宿主病（GVHD）,其中急性GVHD 8例（30.8 %）[Ⅲ～Ⅳ度4例（15.4 %）],慢性GVHD 7例;HLA全相合与 HLA不全相合移植间GVHD发生率差异有统计学意义（P＝0.014）;复发4例;死亡7例。单因素分析结果显示,发生Ⅳ度GVHD、巨细胞病毒（CMV）感染是影响患者生存的高危因素,组间比较差异有统计学意义（P＝0.05和P＝0.027）。结论　allo-HSCT是目前治疗恶性血液病的有效方法,提高allo-HSCT疗效的关键是控制移植相关并发症,特别是GVHD和感染。     

伏立康唑治疗血液病患者侵袭性真菌感染26例疗效观察

侵袭性真菌感染（IFI）是血液系统疾病尤其是恶性血液病治疗过程中常见的并发症。近年来,由于大剂量化疗药物以及免疫抑制广泛应用,血液病患者侵袭性真菌感染（inva-sivefungal infection,IFI）罹患率逐渐增高。而IFI目前诊断手段匮乏,病情进展迅速,病死率高,     

血液肿瘤并发真菌血症23例

 目的　对恶性血液肿瘤并发真菌血症的临床及微生物学特征进行分析,为临床诊治提供参考。方法　对23例恶性血液肿瘤并发真菌血症的临床资料、危险因素、真菌菌群分类以及治疗及预后进行回顾性分析。结果　真菌血症患者病情危重,大多有2种或2种以上的危险因素;菌种分布显示白假丝酵母菌占47 ％;近平滑假丝酵母菌占17 ％;光滑假丝酵母菌占12 ％。23例患者中,13例治愈（56.5％）、8例死亡（34.7 %）;2例放弃（8.6 %）。结论　对有高危因素的恶性血液肿瘤患者应重视真菌血症的发生,积极治疗原发病,加强病原学检测和药敏试验,及时早期诊断并合理选用抗真菌药物可改善预后。     

Efficacy and toxicity of intermediate-dose amphotericin B lipid complex as a primary or salvage treatment of fungal infections in patients with hematological malignancies

We treated 74 adults with a hematological malignancy and documented or suspected invasive fungal infection (IFI) with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Forty-five patients (61%) received upfront therapy and 29 patients (39%) received salvage therapy for their IFI. Forty-eight of 71 evaluable patients responded [complete responses in 40 (56%) and partial responses in 8 (11%)] and 15 (21%) died as a consequence of the IFI. Response rates in invasive aspergillosis were 33 out of 49 (67%) for probable/definite cases and 6 out of 11 (55%) for invasive candidiasis. In 40 patients with neutropenia-associated IFI, rapid neutropenic recovery ( < 10 days from study entry) was essential for response to therapy (90% vs. 32%, P < 0.01). Treatment was well tolerated, with 15% infusions followed by infusion-related adverse events, nephrotoxicity in 7% of patients and 11% of withdrawals due to toxicity. These data suggest that intermediate-doses of ABLC may be of similar efficacy than higher doses with less toxicity, making it a cost-effective alternative worthy of study in future trials.     

侵袭性肺部真菌感染在实体恶性肿瘤与血液肿瘤中发病及抗菌治疗疗效的临床对比分析

目的:对比分析侵袭性肺部真菌感染（IPFI）在实体恶性肿瘤与血液肿瘤患者中的发病率、危险因素、临床特征及抗真菌治疗结果,从而提高对侵袭性肺部真菌感染诊治的认识。方法:回顾性分析2017年6月至2019年6月中国医学科学院肿瘤医院深圳医院实体恶性肿瘤或血液肿瘤合并侵袭性肺部真菌感染并进行抗真菌治疗的患者临床资料,对比两组间的危险因素、临床特征、抗真菌治疗缓解率、用药中位时间差异。结果:实体恶性肿瘤患者合并IPFI 30例,发病率0.42%;血液肿瘤患者合并IPFI 228例,发病率10.6%,差异有统计学意义（P<0.05）。实体恶性肿瘤组和血液肿瘤组男性比例分别为33.3%（10/30）和61.4%（140/228）,多因素分析粒缺状态、有类固醇激素治疗、糖尿病史、慢性肺部疾病史、有咳嗽咳痰症状、G/GM试验阳性率、微生物培养阳性率差异有统计学意义,两组在年龄≥65岁、发热、呼吸困难、肺部特征性影像学表现方面无明显差异。血液肿瘤组中联合抗真菌治疗比例为35.1%（80/228）,实体恶性肿瘤组无,两组患者治疗中位时间为(17.89±7.738)天和(13.55±5.176)天,总有效率为61.5%（91/148）和75%（60/80）,差异有统计学意义(P<0.05)。结论:侵袭性肺部真菌感染在血液肿瘤患者中发病率更高,血液肿瘤联合抗真菌治疗疗效确切且安全,值得在实体恶性肿瘤临床进一步应用。     

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。     

Invasive fungal infection in patients with myelodysplastic syndrome: a report of twelve cases

In this report we analyse the risk factors, clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed a invasive fungal infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year-period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IF, 12 of which (3%) occurred in MDS patients from five of the participating centres. The primary localisation of infection was the lung in 10 cases and skin and paranasal sinus in one case each. Ten patients died at the end of the follow up. The death was mainly attributable to IFI progression in nine of them. The factors which appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localisation at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.     

Neutropenia and invasive fungal infection in patients with hematological malignancies treated with chemotherapy: a multicenter,prospective, non-interventional study in China

In this study, we explored the relationship between neutropenia (absolute neutrophil count (ANC) <1,500/mm³) and invasive fungal infection (IFI) in Chinese patients who had hematological malignancies treated with chemotherapy. We conducted a multicenter, prospective, non-interventional study of consecutive patients with hematological malignancies undergoing chemotherapy in China and determined clinical characteristics of patients who developed neutropenia and IFI. The results indicated that for the 2,177 neutropenic patients, 88 (4.0 %) were diagnosed with IFI. We found that a high risk of IFI (P?<?0.05) is associated with male gender, non-remission of the primary disease, use of two or more broad-spectrum antibiotics, treatment with parenteral nutrition, presence of cardiovascular disease, history of IFI, and neutropenia. When the ANC was less than 1,000, 1,000～500, 500～100, and <100/mm³, the incidence of IFI was 0.5, 5.2, 3.9, and 4.7 %, respectively (ANC?>?1,000/mm³ versus other groups, P?<?0.001). When the ANC was less than 1,000, 500, or 100/mm³ for 10 days or more, the incidence of IFI was 3.2 versus 6.1 % (P?=?0.0052), 3.5 versus 7.1 % (P?=?0.0021), and 3.1 versus 10.0 % (P?<?0.001). When the ANC was less than 100/mm³, taking antifungal prophylaxis reduced the incidence of IFI (P?<?0.05). The IFI-attributable mortality rate was 11.7 %. In conclusion, Chinese patients with IFI, severe and prolonged neutropenia increases the incidence of IFI. The incidence of IFI associated with neutropenia was reduced when antifungal prophylaxis was given. IFI was associated with a significantly increased high mortality rate in hematological malignancy patients with neutropenia.     

Fungal infections of the central nervous system and paranasal sinuses in onco‐haematologic patients. Epidemiological study reporting the diagnostic‐therapeutic approach and outcome in 89 cases

Invasive fungal infections (IFI) of the Central Nervous System (IFI‐CNS) and Paranasal Sinuses (IFI‐PS) are rare, life‐threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI‐CNS (71/89) and IFI‐PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5‐79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI‐CNS, and a sinus biopsy was performed in 56% of IFI‐PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI‐CNS (30/71), and it was positive in 67%. Eighty‐four pts received a first‐line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5‐835). A surgical intervention was performed in 26% of cases but only 10% of IFI‐CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1‐year overall survival was 32% without significant differences between IFI‐CNS and IFI‐PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI‐CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.     

The role of surgery in the treatment of invasive fungal infection in paediatric haematology patients: a retrospective single‐centre survey

Surgery may improve the control of fungal disease and patient survival. The aim of this study was to report a single‐centre experience in using surgery for the treatment of paediatric invasive fungal infection (IFI). From 2001 to 2009, 18 paediatric onco‐haematology patients underwent 24 surgical procedures as treatment of IFI. At surgery, severe thrombocytopenia and neutropenia were present in four and one episodes respectively. Complications were one pleural effusion, one pleural effusion and surgical wound infection, one pneumothorax with wound dehiscence and one wound dehiscence. None of them required repeat surgery. The median duration of hospitalisation for four complicated procedures was 11 days, range 3–16, and 7 days, range 2–13, for the 20 uncomplicated procedures. No surgery‐related deaths occurred. Fourteen patients resumed chemotherapy after a median of 26 days, range 9–77, whereas nine patients underwent hematopoietic stem cell transplantation after a median of 42 days, range 27–110. At 3 months from IFI, 17 patients were alive (94%) and one patient (6%) died from mycosis; the 3‐month overall survival (OS) being 94.4%, CI 66.6–99.2. After a median follow‐up of 7.1 years (CI 2.8–7.5), the OS was 54.5%, CI 29.2–74.2. Surgery is a feasible and valuable option in paediatric patients because it is associated with a low incidence of complications and an acceptable delay in resuming the chemotherapeutic plan.     

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.     

Filamentous fungi infection in patients with myelodysplastic syndrome. A report of twelve cases

In this report we analyse the risk factors, the clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed an Invasive Fungi Infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients, from 5 of the participating centres. The primary localization of infection was lung in 10 cases and skin and paranasal sinus in 1 case each. Ten patients died at the end of follow up. The death was mainly attributable to IFI progression in nine of them. The factors that appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localization at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.