Division of Internal Medicine, Department of Infectious Diseases Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Am J Med. 2012 Jan;125(1 Suppl):S25-38. doi: 10.1016/j.amjmed.2011.10.009.
Effective management of invasive fungal infections (IFIs) depends on early individualized therapy that optimizes efficacy and safety. Considering the negative consequences of IFI, for some high-risk patients the potential benefits of prophylactic therapy may outweigh the risks. When using a prophylactic, empiric, or preemptive therapeutic approach, clinicians must take into account the local epidemiology, spectrum of activity, pharmacokinetic and pharmacodynamic parameters, and safety profile of different antifungal agents, together with unique host-related factors that may affect antifungal efficacy or safety. Therapeutic drug monitoring is increasingly recognized as important or necessary when employing lipophilic triazoles (itraconazole, voriconazole, posaconazole) or flucytosine. Because early diagnostics remain limited for uncommon, yet emerging opportunistic molds (e.g., Mucorales), and treatment delay is associated with increased mortality, early effective management often depends on a high index of suspicion, taking into account predisposing factors, host cues favoring mucormycosis, and local epidemiology. Antifungal options for mucormycosis are limited, and optimal management depends on a multimodal approach that includes early diagnosis/clinical suspicion, correction of underlying predisposing factors, radical debridement of affected tissues, and extended antifungal therapy. This article discusses strategies for the effective management of invasive mycoses, with a particular focus on antifungal hepatotoxicity.
有效的侵袭性真菌感染(IFI)管理取决于早期个体化治疗,以优化疗效和安全性。鉴于 IFI 的负面后果,对于某些高危患者,预防性治疗的潜在益处可能超过风险。在使用预防性、经验性或先发制人的治疗方法时,临床医生必须考虑当地的流行病学、作用谱、药代动力学和药效学参数以及不同抗真菌药物的安全性概况,以及可能影响抗真菌疗效或安全性的独特宿主相关因素。当使用亲脂性三唑(伊曲康唑、伏立康唑、泊沙康唑)或氟胞嘧啶时,治疗药物监测越来越被认为是重要的或必要的。由于早期诊断仍然有限,用于罕见但新兴的机会性霉菌(例如,毛霉目),并且治疗延迟与死亡率增加相关,因此早期有效的管理通常取决于高度怀疑,考虑到诱发因素、有利于毛霉病的宿主线索和当地流行病学。毛霉病的抗真菌选择有限,最佳管理取决于多模式方法,包括早期诊断/临床怀疑、纠正潜在的诱发因素、受累组织的彻底清创和延长抗真菌治疗。本文讨论了侵袭性真菌感染的有效管理策略,特别关注抗真菌药物的肝毒性。