Mercier Toine, Maertens Johan
J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i29-i38. doi: 10.1093/jac/dkx031.
Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency. An empirical approach, whereby mould-active therapy is started in neutropenic patients with fever unresponsive to broad-spectrum antibiotics, is widely applied but incurs the clinical and cost penalties associated with overtreatment. A benefit for all-cause mortality using empirical therapy has not been shown, but it is recommended for high-risk patients who remain febrile after 4-7 days of broad-spectrum antibiotics and in whom extended neutropenia is anticipated. There is growing interest in delaying antifungal treatment until an invasive fungal infection is confirmed ('pre-emptive' or 'diagnostics-driven' management), prompted by the development of more sensitive diagnostic techniques. Comparisons of empirical versus pre-emptive regimens are sparse, particularly with modern triazole agents, but treatment costs are lower with pre-emptive therapy and the available evidence has not indicated reduced efficacy. Pre-emptive treatment may be appropriate in neutropenic patients who remain febrile after administration of broad-spectrum antibiotics but who are clinically stable. Further work is required to define accurately the specific patient subgroups in which each management approach is optimal.
针对侵袭性真菌病已探索了不同的治疗策略，每种策略都有其独特的优缺点。广谱抗真菌预防似乎合乎逻辑，但由于其存在诸多显著缺点，包括干扰诊断检测、导致耐药性选择、药物毒性和药物相互作用，所以选择性使用很重要。抗霉菌预防应仅限于高危人群，如接受急性髓系白血病或骨髓增生异常综合征强化化疗的患者、既往有侵袭性真菌感染、移植物抗宿主病或长期中性粒细胞减少的异基因造血干细胞移植患者、实体器官移植受者或患有高危遗传性免疫缺陷的患者。一种经验性方法是，对广谱抗生素治疗无效的发热中性粒细胞减少患者开始使用抗霉菌治疗，这种方法被广泛应用，但会带来过度治疗相关的临床和成本代价。经验性治疗对全因死亡率的益处尚未得到证实，但对于使用广谱抗生素4至7天后仍发热且预计会出现长期中性粒细胞减少的高危患者，建议采用经验性治疗。随着更敏感诊断技术的发展，越来越多的人倾向于在确诊侵袭性真菌感染后再进行抗真菌治疗（“抢先”或“诊断驱动”管理）。关于经验性治疗与抢先治疗方案的比较较少，特别是对于现代三唑类药物，但抢先治疗的成本较低，现有证据也未表明其疗效降低。抢先治疗可能适用于使用广谱抗生素后仍发热但临床稳定的中性粒细胞减少患者。需要进一步开展工作，以准确界定每种管理方法最适合的特定患者亚组。
