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Determination of fungicidal activities against yeasts and molds: lessons learned from bactericidal testing and the need for standardization.
Clinical Microbiology Reviews ( IF 36.8 ) Pub Date : 2004-04-16 , DOI: 10.1128/cmr.17.2.268-280.2004
M A Pfaller 1 , D J Sheehan , J H Rex
Affiliation  

In certain unique clinical settings, the ability of the antimicrobial agent administered to kill the pathogen outright may be quite important. These situations invariably involve infection of a site not easily accessed by host defenses and/or of a structure with essential anatomic or physiologic function such as the heart (endocarditis), central nervous system (meningitis), or bone (osteomyelitis). Likewise, infections in immunosuppressed hosts, especially those who are neutropenic, are often thought to require microbicidal therapy. Proof of the cidal nature of an antimicrobial agent in vitro is tedious, complex, and fraught with error. Although several methods for assessing in vitro bactericidal activity have been standardized (NCCLS M26-A and M21-A), the clinical relevance of these determinations is questionable and the tests are performed infrequently in most laboratories. Most of the clinical data supporting the need for microbicidal therapy and testing have focused on bacterial infections. However, given the fact that most serious fungal infections occur in profoundly immunosuppressed individuals, it is generally assumed that a cidal regimen would be preferable in that setting as well. In view of this clinical concern and the perceived need to assess the fungicidal activity of a variety of agents, we considered that it would be useful to review what is known about the issues and problems in assessing bactericidal activity and the clinical utility of such measurements. Following this review, we discuss the issue of how one defines fungicidal activity in vitro and in vivo and how feasible it might be to determine the fungicidal activity of organism-drug combinations for purposes of both drug development and clinical care. Proposed methods for fungal time-kill determinations and minimal fungicidal concentration determinations are also discussed.

中文翻译:

确定针对酵母和霉菌的杀真菌活性:从杀菌测试中学到的经验教训以及对标准化的需求。

在某些独特的临床环境中,所施用的抗菌剂彻底杀死病原体的能力可能非常重要。这些情况总是涉及宿主防御不易进入的部位的感染和/或具有基本解剖或生理功能的结构的感染,例如心脏(心内膜炎),中枢神经系统(脑膜炎)或骨骼(骨髓炎)。同样,通常认为免疫抑制的宿主(尤其是中性粒细胞减少的宿主)中的感染需要杀菌处理。体外抗菌剂杀灭性质的证明是乏味,复杂且充满错误的。尽管已评估了几种评估体外杀菌活性的方法(NCCLS M26-A和M21-A),这些测定的临床相关性值得怀疑,并且在大多数实验室中很少进行测试。支持杀微生物治疗和测试需求的大多数临床数据都集中在细菌感染上。但是,考虑到最严重的真菌感染发生在高度免疫抑制的个体中,通常认为在这种情况下,优选使用杀灭方案。鉴于这种临床关注以及评估各种试剂的杀真菌活性的认识需求,我们认为复习有关评估杀菌活性和此类测量的临床实用性方面的问题和问题的已知知识将是有用的。审核之后,我们讨论了一个问题,即如何定义体外和体内的杀真菌活性以及为药物开发和临床护理目的确定生物-药物组合的杀真菌活性可能是多么可行。还讨论了用于确定真菌杀灭时间和确定最小杀真菌浓度的方法。
更新日期:2019-11-01
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