Combination Therapy for Mucormycosis: Why, What, and How?
Combination Therapy for Mucormycosis: Why, What, and How?
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DOI：
10.1093/cid/cir885
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发表时间：
2012-02-01
影响因子：
11.8
通讯作者：
Walsh, Thomas J.
中科院分区：
文献类型：
--
作者：
Spellberg, Brad;Ibrahim, Ashraf;Walsh, Thomas J.
毛霉病的高死亡率目前可用的单一治疗，特别是在血液病患者，激发了研究抗真菌药物的新组合，以确定是否可能取得更好的结果的兴趣。脂质多烯-棘白菌素联合治疗是这些方案中最有希望的，基于安全性、棘白菌素肠外制剂的可用性、它们在毛霉病小鼠模型中的协同作用，以及观察性临床数据一致。其他选择包括脂质多烯联合去铁宁或泊沙康唑治疗。需要明确的、随机的、安慰剂对照的III期临床试验来确定这些选择中的任何一种联合治疗是否优于单一治疗。在进行这样的研究之前，临床医生将继续处于不知道是否以及何时进行联合治疗的不可接受的境地。如果联合治疗确实更好但不使用，这种混淆状态可能导致治疗不足；相反，如果联合治疗不更好但使用，可能会导致患者无法接受的毒性和成本。至关重要的是，赞助者必须拿出资金进行这些临床试验，以确定这些毁灭性感染的结果是否可以得到改善。
The high mortality rate of mucormycosis with currently available monotherapy, particularly in hematology patients, has stimulated interest in studying novel combinations of antifungal agents to determine whether superior outcomes might be achieved. Combination lipid polyene-echinocandin therapy is the most promising of such regimens based on safety profile, the availability of parenteral formulations of echinocandins, their synergy in murine models of mucormycosis, and observational clinical data that are concordant. Other options include combination lipid polyene plus deferasirox or posaconazole therapy. Definitive, randomized, placebo-controlled phase III clinical trials are needed to determine whether combination therapy with any of these options is superior to monotherapy. Until such studies are conducted, clinicians will continue to be placed in the unacceptable position of not knowing if and when to administer combination therapy. Such a state of confusion may lead to undertreatment if combination therapy is indeed superior but is not used and, conversely, may lead to unacceptable toxicity and cost to patients if combination therapy is not superior but is used. It is critical that sponsors step forward with funding to conduct these clinical trials to determine whether outcomes from these devastating infections can be improved.