Iwata K
Department of Bacteriology, Faculty of Medicine, University of Tokyo, Japan.
Eur J Epidemiol. 1992 May;8(3):407-21. doi: 10.1007/BF00158576.
Since the therapy of the mycoses, particularly the systemic mycoses, is relatively long-term in nature, emergence of resistance to antifungal drugs during the treatment of period would be of considerable clinical importance. However, most reports of resistance to antifungal agents among human pathogenic fungi indicate that naturally-occurring resistance is very rare, and that the induction of resistant mutants or variants is much more difficult to achieve in vitro and in vivo than with bacteria. As a matter of fact, amphotericin B and some other classic antifungals have not as yet posed a broadly significant problem relative to drug resistance despite their widespread and frequent use. Fungal resistance has thus received little attention, in contrast to the critical importance of bacterial resistance frequently caused by a variety of antibacterial chemotherapeutic agents, until a single exception to this generalization arose with the advent of flucytosine. This new development has aroused great interest in the problem of fungal resistance among the scientists involved with medical mycology. It is generally believed that fungi, like bacteria, are intrinsically capable of developing resistance to antifungal agents. As illustrated by flucytosine, inherently resistant mutants to antifungals occur within sensitive strains of human pathogenic fungi with significant frequency. Given the relatively high degree of such primary resistance, these mutants should develop secondary resistance during therapy, thus resulting in considerable limitations in the clinical usefulness of the antifungals. Virtually, all unsuccessful cases of mycoses treated with some of the recently exploited antifungal drugs, albeit scarce to date, would obviously be attributable to the occurrence of secondary resistance. The exploitation of new antifungal drugs thus requires investigations of their resistance as one of the most important research projects to be undertaken before receiving approval for use on humans. This paper reviews from various aspects the literature on resistance to various classic and novel antifungal agents among human pathogenic fungi. The resistance of some nonpathogenic fungi to these agents will also be described from genetic and biochemical points of view.
由于真菌病，尤其是全身性真菌病的治疗本质上相对长期，因此在治疗期间出现对抗真菌药物的耐药性具有相当重要的临床意义。然而，大多数关于人类致病真菌对抗真菌剂耐药性的报告表明，天然存在的耐药性非常罕见，而且在体外和体内诱导耐药突变体或变体比细菌要困难得多。事实上，尽管两性霉素B和其他一些经典抗真菌药广泛且频繁使用，但相对于耐药性而言，它们尚未构成广泛的重大问题。因此，与各种抗菌化疗药物经常引起的细菌耐药性的关键重要性形成对比的是，真菌耐药性很少受到关注，直到氟胞嘧啶出现才出现了这一普遍规律的唯一例外。这一新进展引起了从事医学真菌学研究的科学家们对真菌耐药性问题的极大兴趣。人们普遍认为，真菌与细菌一样，本质上能够产生对抗真菌剂的耐药性。如氟胞嘧啶所示，人类致病真菌敏感菌株中固有地存在对抗真菌药的耐药突变体，且频率相当高。鉴于这种原发性耐药的程度相对较高，这些突变体在治疗期间应会产生继发性耐药，从而导致抗真菌药的临床实用性受到相当大的限制。实际上，使用一些最近开发的抗真菌药治疗真菌病的所有未成功案例，尽管迄今为止很少见，但显然都可归因于继发性耐药的发生。因此，开发新的抗真菌药需要将其耐药性研究作为在获得批准用于人体之前要开展的最重要研究项目之一。本文从各个方面综述了关于人类致病真菌对各种经典和新型抗真菌剂耐药性的文献。还将从遗传和生化角度描述一些非致病真菌对这些药物的耐药性。
