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抗真菌治疗:新出现和不断发展的治疗方法。

Antifungal Therapy: New and Evolving Therapies.

机构信息

Department of Pharmacy, Strasbourg University Hospital, Strasbourg, France.

Department of Oncology and Hematology, Strasbourg University Hospital, Strasbourg, France.

出版信息

Semin Respir Crit Care Med. 2020 Feb;41(1):158-174. doi: 10.1055/s-0039-3400291. Epub 2020 Jan 30.

Abstract

Invasive fungal diseases primarily occur in immunocompromised patients. Immunosuppression has become more prevalent due to novel treatments, and this has led to a rise in the incidence of invasive fungal diseases. The antifungal armamentarium has long been insufficient and has taken quite some time to become diverse. Antifungal spectrum, tolerability, and toxicity are critical issues. Amphotericin B and its lipid formulations still have the widest spectrum, but, in spite of the better tolerance of the lipid formulations, toxicity remains a drawback, mostly with regard to renal function. Azoles constitute a heterogeneous antifungal class, in which newer molecules have an improved spectrum of activity. The main concern for the clinician when using azoles relates to the management of their many potential drug-drug interactions in an often fragile patient population. Echinocandins are better tolerated but possess a narrower antifungal spectrum and lack an oral route of administration. Still, their fungicidal activity makes them a weapon of first choice against species. For certain uncommon fungal infections, antifungals such as flucytosine and terbinafine can also be useful. This article will give an overview of the mechanisms of action of currently used antifungals, as well as their spectrum of activity, clinically relevant pharmacological features, drug-drug interactions, and frequent side effects, all of which should drive the clinician's choice of agent when managing invasive fungal infections.

摘要

侵袭性真菌病主要发生在免疫功能低下的患者中。由于新的治疗方法,免疫抑制变得更加普遍,这导致侵袭性真菌病的发病率上升。抗真菌药物的范围一直不足,而且需要相当长的时间才能变得多样化。抗真菌谱、耐受性和毒性是关键问题。两性霉素 B 及其脂质制剂仍然具有最广泛的谱,但尽管脂质制剂的耐受性更好,但毒性仍然是一个缺点,主要与肾功能有关。唑类药物构成了一个异质的抗真菌类,其中更新的分子具有改善的活性谱。当临床医生使用唑类药物时,主要关注的是在经常脆弱的患者群体中管理它们许多潜在的药物相互作用。棘白菌素类药物的耐受性更好,但抗真菌谱较窄,且无口服给药途径。尽管如此,它们的杀菌活性使它们成为对抗某些真菌的首选药物。对于某些罕见的真菌感染,氟胞嘧啶和特比萘芬等抗真菌药物也可能有用。本文将概述目前使用的抗真菌药物的作用机制,以及它们的活性谱、临床相关的药理学特征、药物相互作用和常见的副作用,所有这些都应该促使临床医生在治疗侵袭性真菌感染时选择合适的药物。

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