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。     

Fungal infections in children with human immunodeficiency virus infection

The increasing prevalence of fungal infections is caused in large part by the human immunodeficiency virus (HIV) epidemic. HIV-associated immunodeficiency is a major risk factor for invasive fungal disease. The prevalence of fungal infections in adults with HIV infection is markedly increased, and a large body of information about their incidence, course, and prognosis in adults exists. However, fungal infections, except candidiasis, are less common in children with HIV infection, and information about their pathogenesis is limited. The reason for this difference is unknown. This article reviews the occurrence of systemic fungal infections in children with HIV infection. Despite the relative rarity of infections with the ubiquitous and endemic fungi in the first 2 decades of the HIV epidemic, the increasing number of children with long-standing HIV infection in the era of highly active antiretroviral therapy warrants close surveillance for and aggressive treatment of fungal infections in children with HIV infection. Copyright © 2001 by W.B. Saunders Company     

Fungal colonization and infection in children with acute leukemia and lymphoma during induction therapy

BACKGROUND: Fungal infection represents a growing problem in children with hematologic malignancies. During chemotherapy induced neutropenia, colonization with fungi is considered a major risk factor for subsequent fungal infection. The rates and risk factors for mycotic infections in pediatric oncology patients is undetermined, particularly for centers in developing countries. The aim of this study was to evaluate the rates and risk factors of fungal colonization in children with acute leukemia and lymphoma at one of the major pediatric hematology/oncology centers in Turkey. PROCEDURE: Fifty-two consecutive children newly diagnosed with acute leukemia and lymphoma during intensive remission induction therapy were evaluated for the occurrence of fungal colonization (defined as at least one positive surveillance culture) and infection. RESULTS: Thirty-six of the 52 patients (69.2%) were colonized by Candida albicans which was the only fungus isolated from surveillance cultures. There were three (5.8%) proven systemic fungal infections: two cases of candidemia and one case of brain abscess with Aspergillus spp. isolated from tissue. All patients with fungal colonization were receiving prophylactic or curative antibiotics. No significant association was found between type of disease and fungal colonization, but there was a significant association with neutropenia. CONCLUSIONS: Our findings suggest that there is a high rate of fungal colonization in children receiving remission induction therapy for acute leukemia and lymphoma. Limiting the use of antibiotics and instituting antifungal chemoprophylaxis may decrease the rate, while the early initiation of empiric antifungal therapy in patients with fever and suspected mycotic colonization may increase survival in these patients.     

Treatment of fungal infections in neutropenic children

Fungal infections have emerged as one of the most significant complications of antineoplastic therapy and marrow transplantation in children. Morbidity and mortality associated with fungal infections are high. Recent trends indicate that the incidence and spectrum of fungal infections are increasing, partly because of the increase in the number of children receiving intensive chemotherapy and marrow transplantation, but also because of the successful management of bacterial and viral infections. Though many factors may contribute to risk for developing a fungal infection, prolonged neutropenia is the most important. Until recently, options for antifungal therapy were limited. Advances include less toxic formulations of amphotericin B and an expanding armamentarium of azoles as well as new antifungal compounds. This review addresses the therapeutic options available for treatment of fungal infections in immunocompromised children.     

儿童侵袭性肺部真菌感染

近年来,儿童侵袭性肺部真菌感染病例有上升趋势,早期诊断和及时治疗对于降低病死率非常重要.本文介绍了儿童侵袭性肺部真菌感染的发生因素、临床和影像学表现、微生物检查、诊断和治疗,以期提高对本病的诊治水平.     

儿童侵袭性肺部真菌感染

近年来,儿童侵袭性肺部真菌感染病例有上升趋势,早期诊断和及时治疗对于降低病死率非常重要.本文介绍了儿童侵袭性肺部真菌感染的发生因素、临床和影像学表现、微生物检查、诊断和治疗,以期提高对本病的诊治水平.     

Conventional vs. Liposomal Amphotericin B in Immunosuppressed Children

Invasive fungal infections, mostly caused by Candida and Aspergillus species, are a major cause of early morbidity and mortality in immunocompromised children. 1,2 The treatment of choice for systemic fungal infections is still the early intravenous administration of amphotericin B. 3 However, conventional AMB therapy is often limited by severe side effects such as fever, chills, bronchospasm, and nephrotoxicity. 2 In recent reports liposomal AMB (AmBisome) was shown to be effective in the treatment of severe systemic fungal infections. 4,5 So far, clinical experience with AmBisome in children is still anecdotal and no comparative study is yet available. In the following we report on 11 immunosuppressed children who were treated with conventional or liposomal AMB for longer than 3 weeks.     

Chronic granulomatous disease presenting with disseminated intracranial aspergillosis

We describe an 8-year-old boy who presented with multiple unresectable aspergillus brain abscesses as the initial presentation of X-linked chronic granulomatous disease (CGD). He failed initial therapy with amphotericin B, but was subsequently salvaged with voriconazole. CGD should be considered in the differential diagnosis for all children presenting with invasive fungal infections, particularly, those involving the central nervous system (CNS). Whereas, optimal pharmacologic therapy is still unknown for CNS aspergillosis, voriconazole may have an advantage due to its ability to cross the blood brain barrier and excellent oral absorption and bioavailability.     

Pulmonary aspergillosis and chronic septic granulomatosis]

Two children with chronic granulomatous disease who developed diffuse pulmonary aspergillosis are described. The outcome was satisfactory in one case with miliary disease because the diagnosis was made early by an open lung biopsy. In the other case the diagnosis was delayed and the child died after 7 months with disseminated haematogenous spread of the fungal infection. Although most of the infections of chronic granulomatous disease are bacterial, the abnormalities of phagocyte killing will also predispose to fungal infections. The prolonged survival of affected children because of antibiotic therapy will increase the risk of parasitic and fungal infections.     

儿童侵袭性真菌感染的临床特征及病原菌分析

目的：探讨儿童侵袭性真菌感染的临床特征及病原菌分布。方法：回顾性分析2008～2012年间诊断为侵袭性真菌感染的104例患儿的临床资料。结果：104例患儿中,新生儿20例,婴幼儿48例,学龄前期及学龄期儿童（年长儿）36例。新生儿组中,早产儿比例较高（70%）;多患有肺透明膜病（45%）、肺炎（30%）等基础疾病;给予全胃肠外营养的患儿比例较其他两个年龄组高（P<0.01）。新生儿组及婴幼儿组机械通气比例明显高于年长儿组（P<0.05）。年长儿组多为血液恶性肿瘤患儿,粒细胞减少及接受化疗的患儿比例较其他两个年龄组高（P<0.05）。感染部位以肺部多见（61.5%）,其次为败血症（14.4%）、肠道（12.5%）,神经系统感染仅见于年长儿。104例患儿中共分离出105株真菌,包括假丝酵母菌 90株,隐球菌6株和其他真菌9株,以白色假丝酵母菌最多（52/105,49.5%）,非白色假丝酵母菌比例也较高（38/105,36.2%）。假丝酵母菌对5-氟胞嘧啶及两性霉素B的敏感性较高,对三唑类药物敏感性相对较低。结论：侵袭性真菌感染可发生于各年龄儿童,各年龄组间危险因素有异同;假丝酵母菌是其主要病原菌,白色假丝酵母菌所占比例高,非白色假丝酵母菌也占较高比例。假丝酵母菌对5-氟胞嘧啶和两性霉素B较为敏感。     

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。     

儿童实体瘤合并侵袭性真菌感染3例临床分析

目的总结实体瘤患儿合并侵袭性真菌感染的诊断与治疗经验。方法回顾性分析3例实体瘤患儿于化疗过程中合并侵袭性真菌感染的临床特点及诊治经过。结果 3例实体瘤患儿均于多疗程化疗后发生肺部真菌感染,其中1例合并其他部位感染。3例患儿均有发热、中性粒细胞缺乏,曾使用广谱抗生素、激素治疗。3例患儿血真菌培养均为阳性,其中近平滑假丝酵母菌2例,白色念珠菌1例,1-3-β-D葡聚糖检测结果明显升高。3例患儿肺部CT均表现为密度增高、渗出炎症阴影。2例患儿治疗后好转存活,1例经治疗好转后,因肿瘤多发转移而死亡。结论肺部真菌感染为儿童实体瘤合并侵袭性真菌感染的常见表现形式,多发生于多次化疗后骨髓抑制期;临床表现缺乏特异性,需结合病史、实验室及影像学检查作出诊断;可疑侵袭性真菌感染时应及时进行经验性治疗。[临床儿科杂志,2012,30(5):425-427]     

OPPORTUNISTIC INFECTIONS IN PEDIATRIC HIV INFECTION: A study of 74 Autopsy Cases from Latin America

The present report describes opportunistic infections found at 74 autopsies of pediatric HIV AIDS patients performed at several hospitals in Latin American countries. Fungal infections were the most common (53 cases), Candida sp. (39.18 ) and Pneumocystis carinii (20.27 ) being the most frequently recognized. Other fungal diseases included histoplasmosis, aspergillosis, and cryptococcosis. Viral infections were present in 31 cases, 38.7 being due to cytomegalovirus. Other viruses recognized included herpes simplex and adenovirus. Additional opportunistic infections were due to Mycobacterium avium-intracellulare, toxoplasmosis, and tuberculosis. Nonspecific bacterial bronchopneumonia was present in 11 cases. Cytomegalovirus and P. carinii coinfection was the most common association found. In this series patients died at a younger age (72 at or younger than 1 year old) and there was a slightly higher number of cases of histoplasmosis and brain toxoplasmosis than in other previously published series of infants and children.     

Inflammatory tinea pedis/manuum masquerading as bacterial cellulitis

BACKGROUND: Tinea pedis and tinea manuum in children are more common than previously recognized. Clinical presentations of dermatophyte infections may vary in children and may be difficult to diagnose. OBJECTIVE: To show the necessity of potassium hydroxide preparations and/or fungal cultures in assessing suspicious cases of cellulitis in children who may have dermatophyte infections. PATIENTS: We describe 4 children with inflammatory tinea pedis or tinea manuum who were initially misdiagnosed as having bacterial cellulitis. INTERVENTION: A potassium hydroxide examination was performed on 3 patients. Fungal cultures were performed on 2 patients. RESULTS: Inflammatory/bullous dermatophyte infections were detected by potassium hydroxide examination in all 4 patients and all 4 children successfully responded to topical antifungal therapy. CONCLUSIONS: These cases demonstrate that inflammatory tinnea pedis/manuum can masquerade as cellulitis in children. Early potassium hydroxide examination can allow appropriate antifungal treatment to be initiated before fungal culture results are finalized.     

儿科抗真菌药物的合理使用

近20年来,随着广谱抗菌药物、免疫抑制剂、激素、抗肿瘤药物和靶向生物制剂的广泛应用以及真菌检测方法的不断改进,儿童侵袭性真菌病的发病率呈逐年上升趋势,侵袭性真菌病成为免疫低下儿童的主要死亡原因之一。除了原发性免疫缺陷、肿瘤、造血干细胞移植、实体器官移植及获得性免疫缺陷综合征病毒(HIV)感染等,婴幼儿本身也是真菌感染的高危因素。因此早期诊断、及时应用有效抗真菌药是挽救患儿生命的重要措施。儿童作为特殊人群,抗真菌药物的选择和剂量与成人不同,该文主要探讨如何选择合适的抗真菌药物来预防和治疗儿童真菌病。     

Caspofungin for invasive fungal infections: combination treatment with liposomal amphotericin B in children undergoing hemopoietic stem cell transplantation

Abstract:  Invasive fungal infections often prove difficult to eradicate especially in the stem cell transplant setting. Amphotericin has been the mainstay of treatment for years but has significant toxicity. Newer antifungal agents, such as caspofungin, have shown promising results in adults, particularly when used in combination with amphotericin as both drugs differ in their mode of action. However, there are few data from children and no previous published information about the use of Caspofungin after paediatric stem cell transplantation. We report our experience in children with proven invasive fungal infections after stem cell transplantation. This combination was non-toxic, and two of three patients survived their infections.     

Fluconazole for treatment of fungal infections of the urinary tract in children

Two children with fungal urinary tract infections (UTI) were treated with fluconazole. One had bilateral megaureters, an almost non-functioning right kidney, and a moderately functioning left kidney because of severe vesicoureteric reflux. He underwent a ureteric reimplantation procedure but developed a fungal UTI postoperatively. The other child had bilateral refluxing megaureters, one of which appeared to open ectopically into the urethra. He acquired a fungal infection during intensive and prolonged antibiotic therapy for a bacterial UTI and septicaemia in the neonatal period. Both fungal infections were cured successfully. We recommend fluconazole as a safe and effective antifungal agent that may be used as a drug of choice for this difficult problem.     

Neutrophil function in children with acute lymphoblastic leukaemia in the presence and absence of viral infections.

Neutrophil function was assessed regularly in 26 children with acute lymphoblastic leukaemia (ALL) in remission, both when they were well and during viral infections. Tests of candidacidal ability when these children were apparently free of infection showed a trend towards lower levels compared with controls. The most pronounced depression of candidacidal ability and chemotaxis was during viral infections, and these two functions of neutrophils were more likely to be abnormal then than when the children were free of infection. In children with ALL in remission, whose neutrophils may function abnormally even when they are well, the risk of acquiring bacterial or fungal infections may be made greater by virus infections.     

Current approaches to diagnosis and treatment of fungal infections in children infected with human immuno deficiency virus

The prolonged survival of profoundly immunocompromised patients has revealed mucosal and invasive fungal infections to be major causes of morbidity and mortality in advanced HIV disease in children of all age groups. Antifungal resistance has become a clinically relevant problem. Paediatricians caring for HIV-infected children need to be aware of these increasingly frequent and often life-threatening infectious complications. This article reviews what is currently known about epidemiology, clinical presentation, diagnosis and treatment of mucosal and invasive fungal infections in children and adolescents with HIV disease. Candida spp. have become a leading bloodstream isolate in hospitalised patients; mucosal candidiasis is the most prevalent opportunistic infection in HIV-infected patients, and in both invasive and superficial infections, non Candidaalbicans spp. are on the increase. Invasive pulmonary aspergillosis has surfaced as an HIV-associated complication and previously uncommon fungi are more frequently encountered. HIV-infected individuals are particularly susceptible to Peumocystis carinii, Cryptococcus neoformans and infections by endemic fungi, such as Histoplasma capsulatum, Coccidioides immitis, Penicillium marneffei, and others. Newer immunological and molecular-based methods provide early and rapid diagnosis and monitoring. Potent and broad-spectrum third generation triazoles and novel fungicidal lipopeptides of the echinocandin class of antifungal antibiotics have entered clinical trials. Immunmodulation by recombinant cytokines and antifungal vaccines are very actively pursued inroads to adjunctive and preventive immunotherapy. Conclusion Mucosal and invasive fungal infections will remain important complications in HIV-infected children of all age groups. Interventional studies and well documented case series are needed to improve the molecular diagnosis, treatment and prevention of invasive fungal infections in the paediatric HIV-infected population. Received: 13 June 1998 / Accepted: 14 July 1998     

Efficacy and safety of itraconazole use in infants

Background

Itraconazole has been used to treat fungal infections, in particular invasive fungal infections in infants or neonates in many countries.

Data sources

Literature search was conducted through Ovid EMBASE, PubMed, ISI Web of Science, CNKI and Google scholarship using the following key words: “pediatric” or “infant” or “neonate” and “fungal infection” in combination with “itraconazole”. Based on the literature and our clinical experience, we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy.

Results

Of 45 articles on the use of itraconazole in infancy, 13 are related to superficial fungal infections including tinea capitis, sporotrichosis, mucosal fungal infections and opportunistic infections. The other 32 articles are related to systemic fungal infections including candidiasis, aspergillosis, histoplasmosis, zygomycosis, trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila.

Conclusion

Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants. With a good compliance, it is cost-effective in treating infantile fungal infections. The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.