Groll A H, Ritter J
Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie/Onkologie, Universitätsklinikum Münster.
Klin Padiatr. 2005 Nov;217 Suppl 1:S37-66. doi: 10.1055/s-2005-872501.
Invasive fungal infections are important causes of morbidity and mortality in pediatric cancer patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of fungal infections including Pneumocystis jiroveci. They are based on specific pediatric pharmacological and regulatory considerations and on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA). Recommendations for the most frequent clinical entities are summarized here. Options for initial therapy of uncomplicated candidemia include deoxycholate amphotericin B (DAMB), fluconazole (FLC), liposomal amphotericin B (LAMB), the combination of DAMB plus FLC as well as voriconazole (VCZ) for patients > 11 years. For acute disseminated candidiasis, the combination of DAMB plus flucytosine is recommended. Indwelling central venous catheters serve as infectious nidus and should be removed whenever feasible. First-line therapy for presumed or proven invasive Aspergillus infections in patients 12 years and older is VCZ with DAMB and LAMB serving as alternatives. Choices for patients < 12 years of age are essentially limited to DAMB and LAMB. Due to the yet lacking evidence for enhanced antifungal efficacy and the ongoing dosage finding of caspofungin (CAS) in pediatric patients, combination therapies (LAMB plus CAS or VCZ plus CAS) should only be considered for fulminant or massive, life threatening infections. In granulocytopenic patients, adjunctive therapy with colony-stimulating factors (G-CSF) is recommended. In patients under immunosuppressive therapy, glucocorticosteroids ought to be reduced or discontinued, if feasible. Surgical interventions are restricted to specific indications. Zygomyces infections are an indication for high-dose LAMB. The combination of DAMB plus flucytosine is the initial treatment of choice of cryptococcal mengoencephalitis, and for treatment of Pneumocystis jiroveci pneumonitis, trimethoprim/sulfamethoxazol or intravenous pentamidine is recommended. Beyond the listed entities, the article provides a brief review on the pharmacokinetics and dosing of antifungal agents in children and adolescents as well as detailed discussions and evidence-based recommendations for empirical antifungal therapy, diagnosis and treatment of superficial fungal infections, of invasive infections by previously rare fungal pathogens and endemic moulds and for adjunctive immunomodulatory and surgical interventions.
侵袭性真菌感染是患有血液系统恶性肿瘤的儿科癌症患者以及异基因造血干细胞移植后发病和死亡的重要原因。本文提供了德国儿科传染病学会（DGPI）和德国儿科血液学/肿瘤学会（GPOH）传染病工作组对于包括耶氏肺孢子菌在内的真菌感染的诊断和治疗建议。这些建议基于特定的儿科药理学和监管考量以及使用美国传染病学会（IDSA）规定的证据标准的临床试验、病例系列和专家意见的结果。此处总结了最常见临床情况的建议。单纯性念珠菌血症的初始治疗选择包括去氧胆酸盐两性霉素B（DAMB）、氟康唑（FLC）、脂质体两性霉素B（LAMB）、DAMB加FLC的联合用药以及11岁以上患者使用伏立康唑（VCZ）。对于急性播散性念珠菌病，推荐DAMB加氟胞嘧啶的联合用药。留置中心静脉导管是感染病灶，应在可行时予以拔除。12岁及以上患者疑似或确诊侵袭性曲霉感染的一线治疗是VCZ，DAMB和LAMB可作为替代方案。12岁以下患者的选择基本上仅限于DAMB和LAMB。由于在儿科患者中尚未有证据表明卡泊芬净（CAS）具有增强的抗真菌疗效且其剂量仍在探索中，联合治疗（LAMB加CAS或VCZ加CAS）仅应考虑用于暴发性或严重的、危及生命的感染。在粒细胞减少的患者中，建议使用集落刺激因子（G-CSF）进行辅助治疗。对于接受免疫抑制治疗的患者，如果可行，应减少或停用糖皮质激素。手术干预限于特定指征。接合菌感染是高剂量LAMB治疗的指征。DAMB加氟胞嘧啶的联合用药是隐球菌性脑膜炎的初始治疗选择，对于耶氏肺孢子菌肺炎的治疗，推荐使用甲氧苄啶/磺胺甲恶唑或静脉注射喷他脒。除了列出的情况外，本文还简要回顾了抗真菌药物在儿童和青少年中的药代动力学和给药情况，以及针对经验性抗真菌治疗、浅表真菌感染的诊断和治疗、以前罕见真菌病原体和地方性霉菌引起的侵袭性感染以及辅助免疫调节和手术干预的详细讨论和基于证据的建议。
