Marr Kieren A
Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon 97239, USA.
Curr Opin Infect Dis. 2008 Aug;21(4):409-14. doi: 10.1097/QCO.0b013e328307c7d9.
Infectious complications after hematopoietic stem cell transplant, especially those caused by fungi, contribute to poor outcomes. Availability of new antifungal drugs has led to creative attempts to prevent infections caused by both yeasts and molds with new antifungal prophylaxis strategies; these studies will be reviewed.
Trials evaluating mold-active azoles, posaconazole and voriconazole, demonstrate that invasive aspergillosis infections can be prevented by prophylactic therapy in patients with hematologic malignancies and after allogeneic hematopoietic stem cell transplant. However, issues arise regarding appropriate dosing and levels, drug interactions, and the importance of breakthrough infections caused by organisms that demonstrate microbiologic resistance. Other recent studies evaluating efficacy and safety of aerosolized lipid formulations of amphotericin B demonstrate promise with directed delivery to the lungs; more long-term follow-up safety information is needed to be assured that this strategy is safe late after allogeneic hematopoietic stem cell transplant, in the setting of acute and chronic graft vs. host disease.
Clinicians should consider using new mold-active azole drugs for prophylaxis instead of fluconazole in allogeneic hematopoietic stem cell transplant recipients that have high risks due to prolonged neutropenia and severe graft vs. host disease. More investigations are needed to support other preventive strategies that utilize diagnostic tests and aerosolized delivery of amphotericin B formulations.
造血干细胞移植后的感染并发症,尤其是由真菌引起的并发症,会导致不良预后。新型抗真菌药物的出现促使人们尝试采用新的抗真菌预防策略来预防酵母菌和霉菌引起的感染;本文将对这些研究进行综述。
评估对霉菌有活性的唑类药物泊沙康唑和伏立康唑的试验表明,对于血液系统恶性肿瘤患者和异基因造血干细胞移植后的患者,预防性治疗可预防侵袭性曲霉感染。然而,在合适的剂量和血药浓度、药物相互作用以及由具有微生物耐药性的病原体引起的突破性感染的重要性方面出现了问题。最近其他评估两性霉素B雾化脂质制剂疗效和安全性的研究表明,将其直接输送至肺部具有前景;需要更多长期的随访安全信息,以确保在异基因造血干细胞移植后晚期、急性和慢性移植物抗宿主病的情况下,这种策略是安全的。
对于因长期中性粒细胞减少和严重移植物抗宿主病而具有高风险的异基因造血干细胞移植受者,临床医生应考虑使用新型对霉菌有活性的唑类药物进行预防,而非氟康唑。需要更多研究来支持其他利用诊断检测和两性霉素B制剂雾化给药的预防策略。