Richards Theresa S, Oliver Brian G, White Theodore C
Department of Global Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
J Antimicrob Chemother. 2008 Aug;62(2):349-55. doi: 10.1093/jac/dkn156. Epub 2008 Apr 23.
The purpose of this study was to investigate whether mechanisms of azole resistance in Candida albicans contribute to reduced micafungin activity in vitro.
MICs were determined for a collection of strains with well-characterized mechanisms of azole resistance obtained from systemic, oral and vaginal infections. This collection of strains includes those with resistance-associated phenotypes. All known molecular mechanisms of azole resistance are included in this set of isolates (alone or in combination). Micafungin activity was further investigated for a subset of isolates by agar dilution.
There was no correlation between any of the azole resistance mechanisms or resistance phenotypes and micafungin activity as determined by MIC, even in isolates with cross-resistance to multiple azole drugs. Overexpression of the ABC transporter CDR2 has been suggested to contribute to reduced echinocandin activity in agar dilution studies. By broth microdilution, there was no difference in MIC between the pump overexpressors and the collection as a whole. However, azole-resistant isolates from matched strains exhibited a small increase in their micafungin MICs relative to their susceptible controls. By agar dilution analysis, multiple CDR2-overexpressing strains exhibited reduced growth in the presence of micafungin relative to the laboratory strain SC5314.
Azole resistance mechanisms do not contribute to increased micafungin MIC as determined by broth microdilution. However, within sets of matched isolates, strains overexpressing CDR2 had a slight increase in micafungin MIC. Changes in micafungin susceptibility are associated with CDR2 overexpression in agar dilution tests.
本研究旨在调查白色念珠菌中唑类耐药机制是否会导致其体外米卡芬净活性降低。
对从系统性、口腔和阴道感染中分离得到的一系列具有明确唑类耐药机制的菌株测定最低抑菌浓度（MIC）。该菌株集合包括具有耐药相关表型的菌株。这组分离株涵盖了所有已知的唑类耐药分子机制（单独或组合存在）。通过琼脂稀释法对部分分离株进一步研究米卡芬净活性。
任何唑类耐药机制或耐药表型与通过MIC测定的米卡芬净活性之间均无相关性，即使在对多种唑类药物具有交叉耐药性的分离株中也是如此。在琼脂稀释研究中，ABC转运蛋白CDR2的过表达被认为会导致棘白菌素活性降低。通过肉汤微量稀释法，泵过表达菌株与整个菌株集合的MIC之间没有差异。然而，来自匹配菌株的唑类耐药分离株相对于其敏感对照，其米卡芬净MIC略有增加。通过琼脂稀释分析，相对于实验室菌株SC5314，多个CDR2过表达菌株在米卡芬净存在的情况下生长受到抑制。
通过肉汤微量稀释法测定，唑类耐药机制不会导致米卡芬净MIC升高。然而，在匹配的分离株组中，CDR2过表达的菌株米卡芬净MIC略有增加。在琼脂稀释试验中，米卡芬净敏感性的变化与CDR2过表达有关。
