摘要

每年，真菌感染导致超过250万人死亡，抗微生物药物耐药性的增加使得问题更加严重。由于真菌与人类在生物学上的相似性，目前仅有三大类抗真菌药物。农业中使用的杀菌剂通过引发人类病原真菌的突变，加速了耐药性的发展。新型药物如ibrexafungerp（由GSK开发）和fosmanogepix（辉瑞产品）通过攻击真菌细胞壁，在临床试验中显示出约80%的有效率；olorofim（F2G研发）则通过干扰DNA合成来发挥作用。然而，新近获批的农业杀菌剂ipflufenoquin，其作用机制与olorofim相似，已因交叉诱导耐药性而对临床效果构成威胁。美国、欧盟及亚洲的监管机构现正呼吁在审批杀菌剂时，需充分考虑抗真菌耐药性风险。尽管如此，确保粮食安全（杀菌剂能减少40%的作物损失）与满足医疗需求之间的平衡仍是一大挑战。未来，基因组测序技术和真菌病毒的研究可能为解决这一问题提供新途径。

Fungal infections cause over 2.5 million deaths annually amid rising antimicrobial resistance, yet only three main antifungal drug classes exist due to fungi's biological similarity to humans. Agricultural fungicides accelerate resistance by triggering mutations in human-pathogenic fungi. New drug classes are emerging: ibrexafungerp (GSK) and fosmanogepix (Pfizer) attack cell walls, showing ~80% efficacy in trials, while olorofim (F2G) disrupts DNA synthesis. However, recently approved agricultural fungicides like ipflufenoquin—mechanistically similar to olorofim—already threaten clinical effectiveness by cross-inducing resistance. Regulators in the US, EU, and Asia now urge weighing antifungal resistance risks when approving fungicides, but balancing food security (fungicides prevent 40% crop loss) and medical needs remains critical. Genome sequencing and mycovirus research offer future solutions.