Smith Kyle D, Achan Beatrice, Hullsiek Kathy Huppler, McDonald Tami R, Okagaki Laura H, Alhadab Ali A, Akampurira Andrew, Rhein Joshua R, Meya David B, Boulware David R, Nielsen Kirsten
Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Medical Microbiology, Makerere University, Kampala, Uganda.
Antimicrob Agents Chemother. 2015 Dec;59(12):7197-204. doi: 10.1128/AAC.01299-15. Epub 2015 Aug 31.
Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results (P = 0.52).
对于艾滋病患者，当CD4细胞计数<100个/μl开始接受HIV治疗时，建议进行隐球菌抗原筛查；对于亚临床隐球菌抗原血症患者，建议进行先发氟康唑单药治疗。然而，非洲目前的抗菌药物耐药情况了解有限。我们使用CLSI肉汤微量稀释法检测了2010年至2014年间从乌干达坎帕拉收集的198株临床分离株的抗真菌药物敏感性。与1998年至1999年的两项先前研究相比，这两项研究报告在广泛使用人用氟康唑和农用唑类杀菌剂之前，MIC50为4μg/ml，MIC90为8μg/ml，我们报告氟康唑MIC50上升至8μg/ml，MIC90值为32μg/ml，31%的分离株氟康唑MIC≥16μg/ml。我们观察到两性霉素B的MIC50为0.5μg/ml，MIC90为1μg/ml，其中99.5%的分离株（198株中的197株）仍敏感。在两性霉素B和氟康唑联合诱导治疗的情况下，未观察到MIC与临床结果之间的相关性。我们还分析了隐球菌对舍曲林的敏感性，MIC50为4μg/ml，表明舍曲林是一种有前景的口服、低成本、可获得的新型药物，可能是氟康唑的替代品。虽然CLSI肉汤微量稀释法是标准化结果、限制人为偏差和提高检测能力的理想方法，但在低收入国家往往无法获得。因此，我们还开发并验证了一种可以在资源有限的环境中轻松实施的检测方法，其敏感性结果相似（P = 0.52）。
