<正>临床资料先证者,男,23岁。主因面部、双手足红斑伴疼痛23年,于2012年10月29日就诊我科。患者出生后1个月,无明显诱因双足出现片状角化过度性红斑,其上见大片脱皮;2个月龄时,双手出现类似皮损;1岁时,面部亦出现片状红斑,其上覆细小鳞屑;皮损处自觉疼痛。症状冬重夏轻,且每于感冒、季节交替、身体状况较差时皮损加重,反复发作至今,未进行正规诊治。先证者祖母与外祖母系表姐妹,父

Objective To induce fluconazole resistance in T.asahii by culture in medium containing increasing concentrations of fluconazole,and to evaluate the stability of the induced resistance.Methods Two T.asahii strains with a highest sensitivity to fluoconazole,including a clinical isolate CBS2479 (minumum inhibitory concentration (MIC) =0.25 μg/ml) and an environmental isolate CBS8904 (MIC =1.5 μg/ml),were selected from 11 T.asahii strains stored in the laboratory of the Department of Dermatology,General Hospital of Beijing Military Region.Both strains were respectively and serially subcultured in potato dextrose agar (PDA) medium containing growing concentrations of fluconazole (from 0.5 MIC to 256 μg/ml).E-test was performed to evaluate the susceptibility of T.asahii to fluconazole after each passage.To evaluate the stability of fluconazole resistance,the T.asahii isolates with induced resistance (MIC ＞ 256 μg/ml) were serially subcultured in drug-free PDA medium,and drug susceptibility assay was performed after each subculture.Results After serial culture in PDA medium containing fluconazole,high level of fluconazole resistance (MIC ＞ 256 μg/ml) developed in both of the fluconazole-susceptible T.asahii strains CBS2479 and CBS8904.The MIC value of fluconazole remained unchanged in the fluconazole-resistant strain CBS2479R,but gradually decreased to 64 μg/ml in the other resistant strain CBS8904R after 18-day culture in fluconazole-free PDA medium.Conclusions Fluconazole resistance can be induced in T.asahii strains from different origins by serial culture in medium containing growing concentrations of fluconazole,and the stability of the induced fluconazole resistance varies between strains of different origins.

With the widespread application of azole antifungal agents in clinical practice,azole resistance has become increasingly prominent.Mutations or expression changes of associated genes are the main cause of azole resistance,and also a research focus at home and abroad.Azole resistance-associated genes mainly include genes involved in the ergosterol synthesis pathway such as ERG11,ERG3,drug efflux protein-related genes such as CDR genes encoding ABC proteins and MDR genes encoding MFS pump,and the calcineurin target gene RTA2.However,there is still a controversy about,or no sufficient evidence for,the relationship between azole resistance and some genes,such as the FLU1 gene of Candida albicans and the ERG11 gene of Candida glabrata.Moreover,interstrain differences exist in azole resistance-mediating genes.

OBJECTIVE To observe the in vitro drug susceptibility and pathogenicity of the Trichosporon asahii(T.asahii)strains isolated from different specimen sources so as to provide evidence for the clinical data. METHODS The E-test was performed to determine the MIC value of 12isolates of T.asahii to 6commonly used antibiotics,then the in vitro drug susceptibilities were assessed,the median lethal dose of 7strains of T.asahii was calculated through the animal experiment,and the pathogenicity was evaluated.RESULTS The 12isolates of T.asahii were naturally resistant to flucytosine and anidulafungin,with instable susceptibility to amphotericin B, yet the strains were susceptible to azoles,voriconazole in particularly;the environmental strains were more susceptible to the azoles than the clinical strains.As for the pathogenicity,the pathogenicity of the clinical strains was significantly higher than that of the environmental strains,the clinical strains had 1to 3magnitude orders of median lethal dose greater than the environmental strains,the median lethal dose of BZP 07005was the highest,CBS 7137the lowest.There was also difference in the median lethal dose among the environmental strains or the clinical strains themselves.CONCLUSIONThe differences in both the in vitro drug susceptibility and the pathogenicity between the clinical T.asahii strains and the environmental strains are statistically significant,and the environmental strains have higher drug susceptibility and lower pathogenicity.

目的 从土壤环境中分离阿萨希毛孢子菌环境株,并对其发育形态进行研究,为进一步研究致病性和耐药性等方面的差异奠定基础.方法 在每年的5-9月重庆地区取材,分别应用二氯硝基苯胺玫红氯霉素(DRBC)及酵母麦芽(YM)培养基进行培养,分离出的菌株分别接种于3％尿素酶培养基进行脲酶试验、形态观察,API20和ITS片段扩增等方法进行逐级分离鉴定,观察环境株与临床株(阿萨希毛孢子菌1株,标准菌株号:CBS2479)在发育形态上的差异.结果 从106份土壤样本中成功分离鉴定出1株阿萨希毛孢子菌环境株,肉眼形态:菌落呈灰白色,表面干燥呈粉末状,未见沟回,形态呈圆形,边缘光滑;光镜形态:以链状孢子为主,有少许关节孢子及分生孢子;电镜下形态:孢子呈饱满的圆形或圆柱形,表面可见绒毛样物质和蛋白样物质,孢子间有丝状物质相接,这些形态特点与临床株差异均有统计学意义(P＜0.05).结论 成功从土壤中分离出中国首株阿萨希毛孢子菌环境株,并发现其在发育形态上与临床株有显著性差异.

<正>临床资料患者,男,87岁。主因左足跟丘疹伴疼痛、渗出8个月,左踝部肿胀、结节伴疼痛、渗出1个月,于2012年10月就诊于我科。患者8个月前无意中发现左足跟部一黄豆大小丘疹,无自觉症状,搔抓破溃后,创面长时间不能愈合。至当地诊所就诊,对皮损部分切除后外用抗生素处理,创面仍不愈合,