儿童白血病化疗后合并全身性真菌感染诊断及治疗体会

目的 积累和交流白血病化疗病人合并深部真菌感染时临床经验.方法 总结2年中明确诊断深部霉菌感染病人的诊断过程、方法、临床特征、治疗反应和转归.结果确诊深部真菌感染者共5例,均为白血病患儿,感染前或感染中白血病达完全缓解,特征性表现为发热,抗菌素治疗＞5天无效,轻中度压痛的多发性硬性皮下小结（2/5例）和肝脾肾散布性低密度病灶（3/5例）,需四周以上二性霉素治疗,有明显但可以处理的毒性反应.结论 发热、抗菌素治疗无效、硬性皮下小结和肝脾肾散布性低密度病灶时应考虑深部真菌感染,并给予4周以上二性霉素治疗.     

恶性血液病患儿合并深部真菌感染的临床分析

目的 探讨恶性血液病患儿骨髓抑制期发生深部真菌感染的诊断和治疗。方法 近10年来诊断为恶性血液病合并深部真菌感染的患儿15例，行血培养，骨髓培养，局部组织检查以了解病原菌，并予以抗真菌治疗。结果 从发热到确诊的时间平均为9.7d;15例中13例口腔见特异性真菌感染病灶。10例真菌病原学检查阳性，9例为念珠菌，1例为曲霉素感染；9例氟康唑治疗无效者改用脂质体二性霉素B（L-AMB）后5例治愈；死于真菌感染的患儿共5例。结论 深部真菌感染的早期诊断及治疗困难。死亡率高，口腔特异性病灶是真菌感染的早期临床表现；L-AMB是治疗深部真菌感染的首选药物，临床使用安全有效。     

国产两性霉素B在血液肿瘤儿童合并真菌感染中的应用

目的通过分析合并侵袭性真菌感染的儿童血液肿瘤患者使用国产性霉素B的治疗效果,评价其临床特征和安全性。方法对19例真菌感染儿童患者进行回顾性分析,对感染部位、实验室检查结果及两性霉素B使用方法进行汇总分析。结果19例患者中确诊4例、临床诊断10例、拟诊5例;感染部位呼吸道8例、皮下结节及鼻甲眶周炎各1例、败血症2例、咽壁脓肿及肝脾各1例。3例经治疗后痊愈,9例治疗后病情明显好转,国产两性霉素B临床总有效率为66.67%,不良反应主要是肝功能损害和低血钾。结论只要使用方法正确,国产两性霉素B的不良反应可以被大多数儿童血液肿瘤患者耐受。     

恶性血液病患儿肺部真菌感染的诊疗体会

儿童急性白血病患儿在强化疗后中性粒细胞减少或缺乏阶段出现真菌感染的病例逐年增多,近年来侵袭性真菌感染(IFI)在发热患儿中的构成比例逐渐加大。据部分资料统计化疗间歇期因真菌感染所致发热患儿占到20%以上[1]。由于临床表现不典型、缺乏特异性的早期诊断指标,使临床确诊及选药极其困难、尤其是严重的播散性深部真菌感染治疗难度大、治疗费用高昂,这不仅延误儿童急性白血病的预期化疗疗程,而且严重威胁患儿生命。目前侵入性深部真菌感染已成为儿童白血病诊疗过程中非常棘手的临床问题,在此我们选取今年在我科血液诊疗中心遇到的部分相…     

儿童急性白血病合并中枢神经系统真菌感染5例并文献复习

目的通过5例儿童急性白血病合并中枢神经系统(CNS)真菌感染的临床总结及相关文献复习,提高对本病的认识。方法回顾性分析北京儿童医院收治的5例急性白血病合并CNS真菌感染患儿的临床特点及诊治经过并文献复习。结果(1)4例急性淋巴细胞白血病(ALL)患儿均接受强化疗,1例为急性非淋巴细胞白血病(AML-M2)半相合造血干细胞移植术后,发生CNS真菌感染前均有肺部真菌感染病史,其中2例合并肝、脾、肾真菌感染,1例合并下肢皮肤真菌感染(2)实验室检查3例有病原学依据,1例烟曲霉菌,2例念珠菌,2例无病原学依据。(3)影像学5例患儿均作头颅CTMRI,表现脓肿、梗塞、颅内出血。(4)治疗及预后1例患儿伊曲康唑+脂溶性两性霉素B治疗,2例患儿伏立康唑治疗,2例患儿伏立康唑和两性霉素B联合抗真菌治疗,抗真菌治疗均有效,4例存活,1例死于严重移植物抗宿主病(GVHD)。结论儿童急性白血病合并CNS真菌感染为侵袭性真菌感染的表现形式之一,多半有其他脏器感染,临床表现不典型,可有脑膜炎或脑脓肿症状和体征,诊断困难,CT、MRI影像学检查重要,伏立康唑、两性霉素B抗真菌治疗有效。     

童急性白血病合并中枢神经系统真菌感染5例并文献复习

目的 通过5例儿童急性白血病合并中枢神经系统(CNS)真菌感染的临床总结及相关文献复习,提高对本病的认识.方法 回顾性分析北京儿童医院收治的5例急性白血病合并CNS真菌感染患儿的临床特点及诊治经过并文献复习.结果 (1)4例急性淋巴细胞白血病(ALL)患儿均接受强化疗,1例为急性非淋巴细胞白血病(AML-M2)半相合造血干细胞移植术后,发生CNS真菌感染前均有肺部真菌感染病史,其中2例合并肝、脾、肾真菌感染,1例合并下肢皮肤真菌感染(2)实验室检查3例有病原学依据,1例烟曲霉菌,2例念珠菌,2例无病原学依据.(3)影像学5例患儿均作头颅CT MRI,表现脓肿、梗塞、颅内出血.(4)治疗及预后1例患儿伊曲康唑+脂溶性两性霉素B治疗,2例患儿伏立康唑治疗,2例患儿伏立康唑和两性霉素B联合抗真菌治疗,抗真菌治疗均有效,4例存活,1例死于严重移植物抗宿主病(GVHD).结论 儿童急性白血病合并CNS真菌感染为侵袭性真菌感染的表现形式之一,多半有其他脏器感染,临床表现不典型,可有脑膜炎或脑脓肿症状和体征,诊断困难,CT、MRI影像学检查重要,伏立康唑、两性霉素B抗真菌治疗有效.     

儿童侵袭性真菌感染临床分析

目的 分析、总结儿童侵袭性真菌感染的临床特点,以利早期诊断,改善预后.方法 回顾分析2001年至2007年住院确诊侵袭性真菌感染的6例患儿临床资料.结果 全部患儿伴有基础疾病,并且都有发热.肺部感染4例,CT扫描出现新月征或气环征2例.肺外感染2例.半乳甘露聚糖试验1/5患儿阳性.4/6患儿为曲霉菌感染.主要以二性霉素B或二性霉素B脂质体治疗,4/6患儿治愈,1例死亡.结论 恶性血液系统疾病和严重免疫抑制是儿童侵袭性真菌感染发病的重要因素.患儿临床表现缺乏特异性,应结合影像学及实验室检查全面考虑进行诊断,曲霉菌感染常见.二性霉素B治疗儿童侵袭性真菌感染有效.     

儿童白血病并肝脾脓肿19例

目的提高儿童白血病并肝脾脓肿的早期诊断率、治愈率,降低白血病患儿感染相关病死率。方法选择2000年1月-2007年12月在北京儿童医院血液病中心治疗的白血病并肝脾脓肿患儿19例,对其临床资料进行回顾性分析。分析内容包括白血病并肝脾脓肿患儿的临床表现、诊断依据、病原学数据、抗感染治疗方案、脓肿转归、恢复化疗时机等。结果所有患儿影像学均发现肝脾脓肿时中性粒细胞>1.0×109L-1。7例血培养阳性,8例咽、大便等标本培养阳性,3例行肝脓肿穿刺活检,病原学阴性。综合阳性病原学结果及抗感染疗效,得出真菌性肝脾脓肿7例,细菌性7例,细菌或厌氧菌性5例。随访10 d~2 a 11个月(中位时间9个月),17例患儿临床及影像学显示脓肿好转,其中10例患儿脓肿最终完全吸收。84%的患儿恢复了化疗。结论化疗后中性粒细胞缺乏伴持续发热的白血病患儿,在粒细胞缺乏恢复后应及时进行影像学筛查肝脾脓肿。脓肿病原学诊断提倡早期进行肝脾组织活检,血培养的阳性率不高,要重视其他部位阳性培养结果。细菌或厌氧菌性脓肿经广谱抗生素抗感染治疗预后好,真菌性肝脾脓肿需长期抗真菌治疗。在肝脾脓肿临床好转、中性粒细胞恢复及影像学脓肿好转或无进展情况下尽早恢...     

小儿化脓性肝脓肿45例临床观察

本文报告45例小儿化脓性肝脓肿,以学龄儿童占多数。其感染来源以胆道及呼吸道感染多见。临床表现以发热、右上腹痛、肝肿大、肝区压痛、肝区包块多见,肝脓液培养以葡萄球菌最多。本组内科治疗36例,手术治疗9例,两组均采用两种或三种有效抗菌素联合治疗。对严重中毒症状辅以激素治疗,同时肝穿排脓,输血,维持水电介质平衡等支持疗法。对抗菌素治疗无效者转外科手术治疗。两组总治愈率为73.3%,好转为22.3%,无效为4.4%,多数经内科综合治疗,预后较好。     

儿童真菌感染继发噬血细胞性淋巴组织细胞增生症 3 例分析

目的提高对儿童真菌感染继发噬血细胞综合征的临床认识。方法总结3例确诊为真菌感染继发噬血细胞综合征患儿的相关资料。结果 3例患儿,男2例,女1例,年龄1岁7个月到3岁1个月,均以反复发热为主诉,2例伴咳嗽,1例伴呕吐,体检发现有肝脾及浅表淋巴结肿大。通过病原学检查确诊为真菌感染的时间均是入院后5天,在有效抗真菌治疗无效后进一步诊断为噬血细胞性淋巴组织细胞增生症。患儿血常规检查早期表现为白细胞计数升高,而血小板及血红蛋白不同程度降低。在抗真菌治疗基础上,2例按照HLH-2004方案进行化疗,1例仅增加地塞米松治疗,3例在治疗过程中均使用丙种球蛋白。最终3例患儿均好转出院。结论儿童真菌感染继发噬血细胞综合征临床少见,在抗真菌治疗基础上增加免疫抑制能改善患儿预后。     

Hepatosplenic Candidiasis in Children with Cancer. Three Cases in Leukemic Children and a Literature Review

Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocylosine was successful in two children. At autopsy, one child had signs of active infection. Hi reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up.     

Double invasive fungal infection and typhlitis in children with acute lymphoblastic leukemia

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.     

DOUBLE INVASIVE FUNGAL INFECTION AND TYPHLITIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.     

Toxicity of amphotericin b in children with cancer.

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.     

实体瘤患儿行自体外周血干细胞移植治疗中真菌感染情况

目的通过对31例实体瘤患儿行自体外周血干细胞移植(auto-PBSCT)治疗中真菌感染的情况进行分析,总结其临床特点、诊断与治疗经验。方法回顾性分析2006年5月-2009年12月本院儿科收治的31例实体瘤患儿行auto-PBSCT治疗过程中防治真菌感染的过程。结果 1.Ⅳ期进展期神经母细胞瘤患儿2例行自体外周血干细胞移植过程中经微生物学检查明确并肺部真菌感染,其中1例并脑、肝真菌感染;2例患儿血培养均为近平滑假丝酵母菌;4例患儿行肺部CT检查,表现为密度增高、渗出炎症阴影;1例进展期神经母细胞瘤患儿明确真菌感染后应用氟康唑、两性霉素B脂质体、伏立康唑静脉滴注抗真菌治疗有效,体温正常,度过骨髓抑制期,原发病获得部分缓解;1例进展期神经母细胞瘤患儿因存在颅内、骨骼、脊髓、肺、肝多发转移肿瘤,于自体外周血造血干细胞移植9 d后骨髓抑制期死亡。2.部分缓解期Ⅳ期神经母细胞瘤1例及进展期肝母细胞瘤1例患儿表现为发热、咳嗽、抽搐,怀疑侵袭性真菌感染,给予氟康唑、两性霉素B、伏立康唑治疗后好转度过骨髓抑制期,原发病获得部分缓解。3.余27例实体瘤患儿auto-PBSCT治疗中应用氟康唑预防真菌感染,临床未发生侵袭性真菌感染,1例进展期Ⅳ期神经母细胞瘤患儿因有多脏器转移,且有原发心脏损害,大剂量化疗后骨髓抑制期免疫耐受差,导致多脏器衰竭死亡。余26例实体瘤患儿顺利度过骨髓抑制期,病情获得缓解。结论实体瘤患儿auto-PBSCT治疗中易并真菌感染,需结合病史、血培养、G试验及CT、MRI等影像学检查做出诊断,经验性应用氟康唑、伏立康唑、两性霉素B等可防治真菌感染,原发病严重未缓解者预后差。     

Successful treatment of disseminated Fusarium infection in an immunocompromised child

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.     

Lethal double infection with Acremonium strictum and Aspergillus fumigatus during induction chemotherapy in a child with ALL

Fungal infections are a major cause of morbidity and mortality in patients during chemotherapeutic treatments and malignant hematologic disease. We present a case of a double fungal infection with disseminated Acremonium strictum (A. strictum) and pulmonary Aspergillus fumigatus (A. fumigatus) and its rapid clinical course. A 17-year-old boy with prolonged neutropenia developed a disseminated fungal infection during induction chemotherapy of his acute lymphoblastic leukemia. The infection was rapidly lethal despite neutrophil recovery and early antifungal combination therapy with amphotericin B and caspofungin. Since there are only a few reports about invasive Acremonium infections, we present this case with regard to differences in the clinic pathologic features of Aspergillosis and other opportunistic fungal infections due to Fusarium or Acremonium species.     

Visceral candidiasis in 2 children treated for acute leukemia

The authors report two cases of splenic and hepatosplenic candidiasis occurring during a protracted neutropenia induced by chemotherapy for acute leukemia (lymphoblastic and myeloblastic respectively). Fungal infection was revealed by persistent or recurrent fever after correction of neutropenia. Diagnosis was suggested by findings at abdominal ultrasonography. It was confirmed by histological analysis which, in the first case, required open liver biopsy. In both cases, lack of improvement of splenic lesions despite treatment with Amphotericin B followed by fluconazole led to splenectomy. Both patients received postoperative anti fungal therapy with Ampho B and at one year's follow up, the patient who had the hepatosplenic candidiasis seems to have recovered.     

Disseminated fusarium infection in two neutropenic children]

Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients.Case report 1. – A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment.Case report 2. – A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence.Conclusion. – Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.