背景:我们先前的临床试验表明,使用亚甲蓝(MB)和碘化钾(KI)的抗菌光动力疗法(aPDT)可有效杀死白色念珠菌(C.白色念珠菌)在患有口腔念珠菌病的成年艾滋病患者中,无论生物膜形成或25SrDNA基因型。这项研究评估了aPDT前后白色念珠菌抗真菌药物敏感性和毒力基因表达的变化。探讨影响临床aPDT疗效的相关因素。
方法:将21名患有白色念珠菌病的成年AIDS患者分为a组(400μMMB,N=11)和b组(600μMMB,N=10)。两组均接受两种aPDT治疗,应用MB5分钟,其次是300mMKI,照明30分钟(37.29J/cm²)。在治疗前后收集白色念珠菌分离株,以评估抗真菌药物敏感性(氟康唑,伊曲康唑,氟胞嘧啶,两性霉素B)和基因表达(CAT1,HWP1)。分析外周血测试与aPDT疗效的相关性。
结果:aPDT降低了两性霉素B的最小抑制浓度(MIC)值,氟康唑,和氟胞嘧啶,主要在第一次治疗后显著减少。不同组之间的MIC降低不同,A组显示氟胞嘧啶和氟康唑MIC的下降幅度更大,两性霉素BMIC中的b组。没有观察到CAT1或HWP1表达的显著变化。aPDT的临床疗效与白细胞和中性粒细胞水平呈负相关。
结论:aPDT可有效降低从接受治疗的患者中分离出的白色念珠菌的抗真菌药物的MIC,特别是在第一次治疗之后。降低MIC所需的MB浓度在不同的抗真菌药物中有所不同。aPDT不会改变CAT1或HWP1表达式,其根除白色念珠菌的临床疗效与白细胞和中性粒细胞水平呈负相关。
BACKGROUND: Our previous clinical trial demonstrated that antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) and potassium iodide (KI) effectively killed Candida albicans (C. albicans) in adult AIDS patients with oral candidiasis, regardless of biofilm formation or 25S rDNA genotype. This study evaluated changes in antifungal susceptibility and virulence gene expression in C. albicans before and after aPDT, and explored factors related to clinical aPDT efficacy.
METHODS: Twenty-one adult AIDS patients with C. albicans oral candidiasis were divided into Group a (400 μM MB, N=11) and Group b (600 μM MB, N=10). Both groups received two aPDT treatments, where MB was applied for 5 minutes, followed by 300 mM KI, and illuminated for 30 minutes (37.29 J/cm²). C. albicans isolates were collected before and after treatment to assess antifungal susceptibility (fluconazole, itraconazole, flucytosine, amphotericin B) and gene expression (CAT1, HWP1). Peripheral blood tests were analyzed for correlations with aPDT efficacy.
RESULTS: aPDT reduced minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, and flucytosine, with significant reductions primarily after the first treatment. MIC reductions differed between groups, with Group a showing greater decreases in flucytosine and fluconazole MICs, and Group b in amphotericin B MICs. No significant changes in CAT1 or HWP1 expression were observed. Clinical efficacy of aPDT negatively correlated with leukocyte and neutrophil levels.
CONCLUSIONS: aPDT effectively reduces MICs of antifungal drugs against C. albicans isolated from treated patients, particularly after the first treatment. The concentration of MB required to reduce MICs varies among different antifungal drugs. aPDT does not alter CAT1 or HWP1 expression, and its clinical efficacy in eradicating C. albicans is negatively associated with leukocyte and neutrophil levels.