Baixench Marie-Thérèse, Aoun Naji, Desnos-Ollivier Marie, Garcia-Hermoso Dea, Bretagne Stéphane, Ramires Sandrine, Piketty Christophe, Dannaoui Eric
Université Paris Descartes, Faculté de Médecine, AP-HP, Hôpital Européen Georges Pompidou, Unité de Parasitologie-Mycologie, Paris, France.
J Antimicrob Chemother. 2007 Jun;59(6):1076-83. doi: 10.1093/jac/dkm095. Epub 2007 Apr 27.
A patient with Candida albicans thrush and oesophagitis was treated with high doses of caspofungin but treatment eventually failed. Four C. albicans isolates were serially recovered before and after caspofungin treatment. A microbiological study was performed to characterize these four isolates.
In vitro antifungal susceptibility testing was performed by the EUCAST reference method in RPMI and AM3 and by Etest. Molecular typing of the four isolates was done by sizing three polymorphic microsatellite markers. To look for specific mutations, sequencing of a region of the gene encoding the 1-3-beta-D-glucan synthase was performed for the four isolates.
In vitro antifungal susceptibility testing showed an increase in both caspofungin and micafungin MICs for the two isolates recovered after caspofungin treatment failure. The best discrimination between the pre-treatment and post-treatment isolates was obtained with Etest. Molecular typing of the four isolates showed that the post-treatment isolates with reduced susceptibility were identical to a susceptible pre-treatment isolate, suggesting the acquisition of caspofungin resistance. Sequencing of the gene encoding the 1-3-beta-D-glucan synthase showed a mutation responsible for an amino acid change at Phe-641 that could confer reduced susceptibility to both echinocandins.
Our results indicate that is it useful to perform in vitro susceptibility testing in the cases of clinical failure during caspofungin therapy.
一名患有白色念珠菌鹅口疮和食管炎的患者接受了高剂量卡泊芬净治疗，但最终治疗失败。在卡泊芬净治疗前后连续分离出四株白色念珠菌。进行了一项微生物学研究以鉴定这四株分离菌。
采用欧盟CAST参考方法在RPMI和AM3中以及通过Etest进行体外抗真菌药敏试验。通过对三个多态性微卫星标记进行大小测定对这四株分离菌进行分子分型。为寻找特定突变，对这四株分离菌编码1-3-β-D-葡聚糖合酶的基因区域进行测序。
体外抗真菌药敏试验显示，在卡泊芬净治疗失败后分离出 的两株菌对卡泊芬净和米卡芬净的最低抑菌浓度均升高。使用Etest对治疗前和治疗后分离菌的区分效果最佳。对这四株分离菌的分子分型显示，敏感性降低的治疗后分离菌与一株敏感的治疗前分离菌相同，提示获得了对卡泊芬净的耐药性。对编码1-3-β-D-葡聚糖合酶的基因测序显示，一个导致苯丙氨酸641位氨基酸改变的突变可能使对棘白菌素类药物的敏感性降低。
我们的结果表明，在卡泊芬净治疗期间出现临床失败的情况下进行体外药敏试验是有用的。
