Korem Maya, Reich Shelly, Rahav Galia, Yahav Dafna, Weinberger Miriam, Novikov Anna, Mizrahi Naama, Ben-Ami Ronen
Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel.
Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Mycoses. 2025 Jan;68(1):e70017. doi: 10.1111/myc.70017.
Infections with fluconazole-resistant Candida parapsilosis have been increasing in Israeli hospitals with unclear implications for patient outcomes.
To determine the frequency, mechanisms, molecular epidemiology, and outcomes of azole-resistant C. parapsilosis bloodstream infections in four hospitals in Israel.
PATIENTS/METHODS: C. parapsilosis bloodstream isolates were collected at four hospitals in central Israel during varying periods from 2005 to 2022. Antifungal susceptibility testing was done using CLSI broth microdilution. Risk factors for fluconazole resistance were investigated using logistic regression. ERG11 gene sequencing was performed on all isolates. Genetic relatedness was determined using multilocus microsatellite genotyping. Clinical cure, microbiological eradication, and mortality rates were compared between fluconazole-susceptible and resistant isolates.
A total of 192 patient-specific C. parapsilosis isolates were analysed. Resistance to fluconazole and voriconazole was detected in 80 (41%) and 14 (7.2%) isolates, respectively. The ERG11 Y132F substitution was found in 91% of fluconazole-resistant and 1% of fluconazole-susceptible isolates. Increasing age, intensive care hospitalisation, haemodialysis, and recent exposure to antibiotics were risk factors for fluconazole-resistant C. parapsilosis. Distinct but related genotypes predominated at each centre, indicating extensive dissemination within hospitals and limited transmission among them. Fluconazole resistance was associated with increased likelihood of microbiological failure but no significant difference in clinical cure and mortality.
We found high rates of fluconazole resistance in C. parapsilosis, attributable to nosocomial spread of hospital-specific clones bearing the Y132F substitution. Fluconazole resistance was associated with a higher risk of microbiological but not clinical failure. Strategies to limit nosocomial transmission of C. parapsilosis are needed.
在以色列医院中，对氟康唑耐药的近平滑念珠菌感染病例一直在增加，但其对患者预后的影响尚不清楚。
确定以色列四家医院中耐唑类近平滑念珠菌血流感染的频率、机制、分子流行病学及预后情况。
患者/方法：在2005年至2022年的不同时间段，收集了以色列中部四家医院的近平滑念珠菌血流分离株。采用美国临床和实验室标准协会（CLSI）肉汤微量稀释法进行抗真菌药敏试验。使用逻辑回归研究氟康唑耐药的危险因素。对所有分离株进行ERG11基因测序。采用多位点微卫星基因分型确定基因相关性。比较氟康唑敏感和耐药分离株的临床治愈率、微生物清除率和死亡率。
共分析了192株患者特异性近平滑念珠菌分离株。分别在80株（41%）和14株（7.2%）分离株中检测到对氟康唑和伏立康唑的耐药性。在91%的氟康唑耐药分离株和1%的氟康唑敏感分离株中发现了ERG11基因Y132F位点的替代。年龄增加、入住重症监护病房、血液透析以及近期接触抗生素是氟康唑耐药近平滑念珠菌感染的危险因素。每个中心都以不同但相关的基因型为主，这表明该菌在医院内广泛传播，但医院之间的传播有限。氟康唑耐药与微生物清除失败的可能性增加有关，但在临床治愈率和死亡率方面无显著差异。
我们发现近平滑念珠菌对氟康唑的耐药率很高，这归因于携带Y132F替代的医院特异性克隆的医院内传播。氟康唑耐药与微生物清除失败的风险较高相关，但与临床治疗失败无关。需要采取策略来限制近平滑念珠菌的医院内传播。
