本文選題：外陰陰道假絲酵母菌病　切入點：復(fù)發(fā)性外陰陰道假絲酵母菌病　出處：《昆明醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：①探討外陰陰道假絲酵母菌病(VVC)致病菌株對7種抗真菌藥物的體外實驗敏感性。②探討VVC和復(fù)發(fā)性外陰陰道假絲酵母菌病(RVVC)致病菌株基因分型與抗真菌藥物最小抑菌濃度(MIC)及藥物敏感性之間的價值與關(guān)聯(lián)性。方法與材料：①致病菌株采集自昆明醫(yī)科大學(xué)第一附屬醫(yī)院婦產(chǎn)科門診的VVC和RVVC患者,采用VITEK(?)2、科馬嘉和安圖進(jìn)行致病菌株的菌種鑒定。②藥物敏感性檢測方法為：CLSI的M27-A3,根據(jù)MIC值判斷藥物敏感性.③DNA提取試劑為AxyPrep Blood Genomic DNA miniprep kit,基因分型方法基于25S rDNA。④統(tǒng)計方法：SPSS17.0軟件,采用Kruskal-Wallis H test,Mann-Whitney U test和Fisher's Exact統(tǒng)計方法。P0.05為差異具有統(tǒng)計學(xué)意義。頻數(shù)表和圖用于統(tǒng)計數(shù)據(jù)。結(jié)果：白色假絲酵母菌334例,所占比例最高,其后依次為光滑假絲酵母菌22例,熱帶假絲酵母菌15例,krusei假絲酵母菌12例。在VVC和RVVC致病菌株中,白色假絲酵母菌占主導(dǎo)地位,229株VVC菌株中,白色假絲酵母菌196株(85.6%)；155株RVVC菌株中,白色假絲酵母菌139株(89.7%)。VVC致病菌株中,非白色假絲酵母菌中,光滑假絲酵母菌(7.4%),熱帶假絲酵母菌(3.9%)、克柔假絲酵母菌(3.1%).而在RVVC致病菌株中,熱帶假絲酵母菌(3.9%)、光滑假絲酵母菌3.2%,克柔假絲酵母菌(3.2%).白色假絲酵母菌致病菌菌株在妊娠和非妊娠患者VVC致病菌株中亦占主導(dǎo)地位,分別為(88.7%)和(87.0%),在非妊娠組中,非白色假絲酵母菌致病菌株光滑假絲酵母菌(6.8%),熱帶假絲酵母菌(4.0%)和克柔假絲酵母菌(2.2%),相反,妊娠組中非白色假絲酵母菌致病菌株主要為克柔假絲酵母菌和熱帶假絲酵母菌(3.2%),無光滑假絲酵母菌致病菌株。藥物敏感性結(jié)果顯示,85.4%(286/335)白色假絲酵母菌致病菌株對氟康唑敏感,而僅有28.6%(14/49)非白色假絲酵母菌致病菌株對氟康唑敏感,兩組差異具有統(tǒng)計學(xué)意義(P0.001)。同樣地,76.1%(255/335)白色假絲酵母菌致病菌株對克霉唑敏感,61.2%(30/49)非白色假絲酵母菌致病菌株對克霉唑敏感,兩組差異具有統(tǒng)計學(xué)意義(P=0.011)。相反,非白色假絲酵母菌致病菌株對咪康唑更敏感(P0.001,95.9%(47/49)非白色假絲酵母菌致病菌株對咪康唑敏感,而僅72.5%(243/335)白色假絲酵母菌致病菌株對咪康唑敏感。非白色假絲酵母菌致病菌株對伊曲康唑63.3%(31/49)的敏感性也較白色假絲酵母菌致病菌35.2%(118/335)株高,非白色假絲酵母菌致病菌株對氟康唑也顯示了不同的藥物敏感性,93.3%(14/15)熱帶假絲酵母菌致病菌株較光滑假絲酵母菌致病菌株敏感,差異具有統(tǒng)計學(xué)意義(P0.001)。主要的三種非白色假絲酵母菌致病菌株對5-氟胞嘧啶、咪康唑、兩性霉素B敏感。在WC和RVVC兩組比較中,VVC組對氟康唑的敏感性高于RVVC組, (P=0.04)分別88.8%(174/335)和80.6%(112/335)。然而,VVC組對咪康唑(P=0.001)和兩性霉素B(P=0.007)的敏感性低于RVVC組,5-氟胞嘧啶和克霉唑在兩組中均顯示了較高的敏感性,大于80%的致病菌菌株對這兩種藥物敏感。相反,制霉菌素和伊曲康唑在兩組均敏感性下降,耐藥率大于40%。在妊娠組中,VVC致病菌株對咪康唑(P0.001)和兩性霉素(P=0.028)敏感較非妊娠組高,RVVC致病菌菌株對MCZ(P=0.018),ITR(P=0.013)和NYS(P=0.006)較非妊娠組敏感。335株致病菌株中,309株(92.2%)鑒定為基因型A(450 bp),19株(5.6%)鑒定為基因型B(840 bp),7株(2%)鑒定為基因型C (450 bp and 840 bp),本研究中無片段大小為1040 bp和1080 bp的與都柏林菌屬相關(guān)PCR產(chǎn)物�；蛐虯在VVC和RVVC組所占比例均高,兩組比較無統(tǒng)計學(xué)差異, (P=0.061)。196株VVC致病菌株,89.8%(176/196)為基因型A,10.2%(20/196)為基因型B和C。 139株RVVC致病菌株中,95.7%(133/139)為基因型A,4.3%(6/139)為基因型B和C。非白色假絲酵母菌致病菌菌株中,除1株光滑和2株克柔假絲酵母菌為基因型B外,余均為基因A。分析基因型與抗真菌藥物敏感性相關(guān)性,基因型B和C(16／26,61.5%)對伊曲康唑的敏感性高于基因型A(103/309,33.3%),(P=0.003)。所有包含840bpPCR產(chǎn)物以及三種非白色酵母菌都對5-氟胞嘧啶敏感。基因型B和C的5-氟胞嘧啶和伊曲康唑的MIC值要低于基因型A,兩組差異具有統(tǒng)計學(xué)意義,分別為(P=0.008)和(P=0.003)。基因型A的最低MIC值抗真菌藥物是克霉唑和兩性霉素B,(MIC90=1μg/ml),而基因型B和C的最低MIC值抗真菌藥物是5-氟胞嘧啶,(MIC90=0.475μg/ml)�；蛐虯的最高M(jìn)IC值抗真菌藥物是制霉菌素、咪康唑和伊曲康唑(MIC90=16μg/ml),而基因型B和C的最高M(jìn)IC值抗真菌藥物是制霉菌素(MIC90=10.4μg/ml)。結(jié)論：①白色假絲酵母菌致病菌株是WC和RVVC妊娠或非妊娠患者最常見的致病菌株。②氟康唑和克霉唑?qū)Ψ前咨俳z酵母菌致病菌菌株的作用效果欠佳,因其體外實驗中顯示了比白色假絲酵母菌致病菌株更高的耐藥性。然而,非白色假絲酵母菌致病菌株顯示了對咪康唑及伊曲康唑的藥物敏感性高于白色假絲酵母菌致病菌株。③VVC和RVVC組中,非白色假絲酵母菌致病菌株未發(fā)現(xiàn)不同藥物的敏感性差異。RVVC組白色假絲酵母菌致病菌株對氟康唑的敏感性低于VVC組,這警示我們未來對該藥物的臨床應(yīng)用。另一方面,RVVC組白色假絲酵母菌致病菌株對咪康唑和兩性霉素B的敏感性高于WC組。④非妊娠期致病菌株對制霉菌素、兩性霉素B、咪康唑和伊曲康唑的藥物敏感性要高于妊娠期致病菌株。除伊曲康唑外,所有的唑類藥物在妊娠期致病菌株中均顯示敏感。⑤基因型A在所有的致病菌株中占主導(dǎo)地位,其后依次為基因型B和C�；蛐蜔oVVC和RVVC無相關(guān)性,但對藥物的MIC值及藥物敏感性有一定影響。表達(dá)1組內(nèi)含子的致病菌株可能是對5-氟胞嘧啶藥物敏感性的主要因素,因所有含840 bp PCR產(chǎn)物的白色和非白色假絲酵母菌致病菌株對其敏感。
[Abstract]:Objective: To investigate the vulvovaginal candidiasis (VVC) in vitro sensitivity of pathogenic strains to 7 kinds of antifungal drugs. To explore VVC and recurrent vulvovaginal candidiasis (RVVC) pathogenic strains of genotype and antifungal drugs of minimal inhibitory concentration (MIC) value and the relationship between drugs and sensitivity. Materials and methods: the pathogenic strains collected from the outpatient department of gynecology and obstetrics of the First Affiliated Hospital of Kunming Medical University and VVC RVVC patients with VITEK (?) 2, Antu Jiahe Tacoma identification of pathogenic strains. The drug sensitivity detection method: CLSI M27-A3, according to the MIC value to determine drug sensitivity. The DNA extraction reagent AxyPrep Blood Genomic DNA miniprep kit 25S rDNA., the statistical method based on genotyping methods: using Kruskal-Wallis SPSS17.0 software, H test, Mann-Whitney U test and Fisher's Exact statistics .P0.05 was a statistically significant difference. The frequency table and chart for statistical data. Results: Candida albicans in 334 cases, the highest proportion, followed by Candida glabrata in 22 cases, 15 cases of Candida tropicalis, 12 cases of krusei Candida spp. in VVC and RVVC pathogenic strains of Candida. Albicans is dominant, 229 VVC strains, 196 strains of Candida albicans (85.6%); 155 RVVC strains, 139 strains of Candida albicans (89.7%).VVC in non pathogenic strains, Candida albicans, Candida glabrata (7.4%), Candida tropicalis (3.9%), Candida krusei (3.1%). While in RVVC pathogenic strains of Candida tropicalis (3.9%), 3.2% Candida glabrata, Candida krusei (3.2%). Candida albicans strains of pathogenic bacteria are dominant in pregnant and non pregnant patients with VVC isolates, respectively. For (88.7%) and (87%), in the non pregnant group, non Candida albicans strains of Candida glabrata (6.8%), Candida tropicalis (4%) and Candida krusei (2.2%), on the contrary, in the non pregnant group of Candida albicans strains for c.krusei Candida albicans and Candida tropicalis (3.2%), non Candida pathogenic strains. The drug sensitivity results showed that 85.4% (286/335) of Candida albicans strains sensitive to fluconazole, and only 28.6% (14/49) non Candida albicans strains to fluconazole sensitive, with significant difference between two groups (P0.001) similarly, 76.1% (255/335) of Candida albicans strains sensitive to clotrimazole, 61.2% (30/49) non Candida albicans strains sensitive to clotrimazole, the difference between the two groups had statistical significance (P=0.011). On the contrary, non Candida albicans induced Isolates of miconazole (P0.001,95.9% (47/49) is more sensitive to non Candida albicans strains sensitive to miconazole, while only 72.5% (243/335) of Candida albicans strains sensitive to miconazole. Non Candida albicans strains of itraconazole in 63.3% (31/49) is the sensitivity of Candida yeast 35.2% pathogenic strains (118/335), non Candida albicans strains also showed different sensitivity to fluconazole, 93.3% (14/15) of Candida tropicalis strains were Candida strains sensitive, the difference was statistically significant (P0.001). Three non pathogenic strains of Candida albicans the main 5- of flucytosine, miconazole and amphotericin B in WC and RVVC sensitive. The comparison between the two groups, VVC group of sensitivity to fluconazole was higher than that of group RVVC (P=0.04), 88.8% (174 /335) and 80.6% (112/335). However, VVC group 瀵瑰挭搴峰攽(P=0.001)鍜屼袱鎬ч湁绱燘(P=0.007)鐨勬晱鎰熸，

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