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。     

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…     

儿童急性白血病化疗合并真菌感染探讨

目的探讨儿童急性白血病化疗合并真菌感染的因素及其感染病原学特点。方法白血病并发真菌感染按EORTC诊断标准。分析真菌感染率、感染部位、感染相关危险因素、病原菌特点。结果共17例白血病患儿21次并发真菌感染,急性淋巴细胞性白血病(ALL)13例,急性非淋巴细胞性白血病(AML)4例;合并真菌感染率为27.6%。感染部位主要位于上呼吸道(61.9%)。病原菌培养均示浅表真菌,如白色念珠菌、酵母样菌。化疗阶段是白血病患儿合并真菌感染的重要因素(P<0.05),免疫功能和中性粒细胞绝对值在临床上亦是主要的影响因素。结论白血病患儿合并真菌感染与疾病本身、机体免疫功能低下、中性粒细胞绝对值和化疗阶段相关。因此,免疫支持、早期诊断、及时治疗颇为重要。     

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.     

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。     

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。     

白血病患儿并侵袭性真菌感染25例

目的探讨白血病患儿并侵袭性真菌感染的易感因素、菌种、临床特点及治疗。方法对2002-2006年治疗的25例白血病并侵袭性真菌感染患儿的病前相关诱因、真菌种类、临床特点、治疗方案进行回顾性分析,并进行统计学处理。结果真菌种类包括念珠菌13例,其中白色念珠菌5例,热带念珠菌4例,近平滑念珠菌2例,光滑念珠菌、丝状真菌各1例;曲霉菌6例,其中烟曲霉菌3例,其他3例未能鉴定;镰刀菌1例。影像学诊断5例。感染部位以肺部为主17例（占68%）;其次为真菌血症、皮肤、胸腹联合感染、口鼻腔、颅内。对其易感因素包括化疗药物使用时间、患者中性粒细胞绝对值、抗生素使用时间及种类、免疫功能进行统计学分析,均是引起真菌感染的易感因素。静脉滴注氟康唑治疗5例,死亡5例。静脉滴注两性霉素B治疗8例,死亡5例。单独应用伊曲康唑静脉滴注7例,死亡1例。伊曲康唑联合用药4例,死亡1例。脂质体两性霉素B治疗1例。总病死率48%。结论急性白血病患儿真菌感染的易感因素与化疗药物使用的累计时间、中性粒细胞绝对值、广谱抗生素联合使用时间和种类、免疫功能相关,菌种以念珠菌和曲霉菌最常见,感染部位以肺部最常见。早期经验性治疗可提高患者存活率,伊曲康唑有良好疗效。     

重症监护病房新生儿深部真菌感染临床特点分析

目的 提高新生儿深部真菌感染的临床诊断及经验性治疗水平.方法 选取2008年1月 - 2010年12月期间NICU住院确诊深部真菌感染的21例新生儿为研究对象,分析患儿的临床表现、实验室结果、基础疾病、真菌类别,以及抗真菌治疗效果.结果 患儿基础疾病以肺部疾病最多见,占47.6%;外科手术治疗5例,占23.8%,其中腹部手术者4例.临床表现以喂养不耐受、呼吸暂停、发热和反应差最多见,有19例(90.5%)出现血小板减低,19例(90.5%)超敏CRP增高,白细胞正常13例(61.9%).其中确诊真菌败血症18例(85.7%),真菌脑炎1例(4.8%),尿路感染2例(9.5%).病原菌均为假丝酵母菌.用氟康唑及两性霉素B脂质体治疗,总治愈率71.4%,好转19.1%,死亡9.5%.结论 喂养不耐受、发热、呼吸暂停和反应差是深部真菌感染患儿最多见的临床表现;患儿多数表现有血小板减低及超敏CRP增高,白细胞正常不能排除该病;近平滑假丝酵母菌感染最多见,白假丝酵母菌次之.     

儿童恶性血液病化疗后继发肝、脾霉菌感染超声检查价值

目的了解儿童恶性血液病化疗后继发肝、脾霉菌感染的发生率,提高对化疗后继发肝、脾霉菌感染的超声表现与临床症状的认识。方法复习经活检病理证实的115例非霍奇金氏淋巴瘤(nonHodgkin’slymphoma,NHL)或白血病的临床资料,所有病例均行肝脾超声检查,选出其中10例化疗后继发肝、脾霉菌感染者,分析其化疗前后的超声表现。结果10例中累及肝脏7例,累及脾脏7例。霉菌感染的超声表现为受累脏器内部边界清晰的单发或多发病灶,直径<2cm,10例中呈均匀低回声灶6例(其中1例伴有声影的强回声灶),4例呈牛眼征。抗霉菌治疗后复查,病灶数量减少或消失。结论儿童化疗后继发肝、脾霉菌感染发生率较高,超声能很好显示肝、脾霉菌感染,正确及时地诊断肝、脾霉菌感染有助于化疗的正常进行。     

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.     

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.     

Factitious fungus in two children with cancer receiving liposomal amphotericin

Amphotericin B deoxycholate and liposomal formulations of amphotericin are often started and continued empirically, in immunocompromised hosts, based on the computed tomography findings and the patient's clinical picture. The authors describe two patients with presumed fungal pulmonary nodules, which were progressive despite prolonged treatment with liposomal amphotericin B. At subsequent biopsy, neither had evidence of active fungal disease; rather, the nodules revealed reactive changes and lipid-laden macrophages. These cases underscore the importance of establishing a microbiologic diagnosis in cases of presumed fungal infection.     

Post-traumatic cutaneous mucormycosis in diabetes mellitus. Short-term antifungal therapy

Mucormycosis is infrequently encountered in the pediatric population in any of its forms (nasopharyngeal, disseminated, pulmonary, or cutaneous) and generally is associated with the immunocompromised host. We present an adolescent with poorly controlled diabetes mellitus who developed a progressive skin lesion 3 weeks after a motor vehicle accident. Rhizopus species was isolated from the lesion, and the biopsy revealed a fungal vasculopathy. Control of her diabetes, aggressive surgical intervention and a 10-day course of antifungal therapy (amphotericin B) resulted in a favorable outcome. This article illustrates the importance of considering cutaneous fungal infections, especially those in the class zygomycetes, in the diabetic patient with unusual, severe or persistent skin lesions. Early recognition is essential in order to avoid morbidity and mortality from this unusual opportunistic infection.     

急性白血病合并侵袭性曲霉病的临床治疗

目的探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果3例急性淋巴细胞白血病(ALL)诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2～5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35d,无霉菌复发。结论CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。