van Hal S J, Chen S C-A, Sorrell T C, Ellis D H, Slavin M, Marriott D M
Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia
Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR-Pathology West, Westmead Hospital, Westmead, Sydney, Australia.
J Antimicrob Chemother. 2014 Aug;69(8):2210-4. doi: 10.1093/jac/dku124. Epub 2014 Apr 30.
Species-specific clinical breakpoints (CBPs) for Candida spp. were established following consideration of clinical outcomes in patients with oesophageal candidiasis. We sought to further determine the validity of the current CBPs based on data from a prospective candidaemia study.
All Candida albicans candidaemia episodes in patients enrolled in the Australian Candidaemia Study and who were treated with fluconazole monotherapy were included. Fluconazole MICs were established using Sensititre(®) YeastOne(®).
Two hundred and seventeen evaluable episodes were identified, 93.5% of which occurred in adult patients. Fluconazole was commenced within 72 h of blood culture positivity in 96.3% (209/217) of episodes. Fluconazole doses were appropriate in 89.9% (195/217) of episodes and the median duration of therapy was 14 days (IQR 8-21 days) for the whole cohort. The all-cause 30 day mortality was 19.8% (43/217), with 37.2% (16/43) of deaths attributed to candidaemia. Classification and regression tree (CART) analysis identified a fluconazole MIC target of ≥2 mg/L for infection-related mortality and ≥4 mg/L for overall 30 day mortality. Overall mortality was no different in episodes with isolates above or below the identified MIC target, although there was a trend towards significance (P = 0.051). On univariate analysis, infection-related mortality was significantly increased in C. albicans episodes with an MIC ≥2 mg/L compared with those below this MIC target (20.6% versus 4.9%; P = 0.001). This target remained an independent predictor of infection-related mortality (OR 8.2; 95% CI 2.3-29.7; P = 0.001).
We observed a direct relationship between infection-related mortality and rising fluconazole MIC for C. albicans candidaemia; overall, the data support the EUCAST and revised CLSI fluconazole clinical breakpoints.
在考虑食管念珠菌病患者临床结局的基础上，确定念珠菌属的种属特异性临床断点（CBP）。我们试图根据一项前瞻性念珠菌血症研究的数据，进一步确定当前CBP的有效性。
纳入澳大利亚念珠菌血症研究中所有接受氟康唑单药治疗的白色念珠菌血症发作病例。使用Sensititre® YeastOne® 确定氟康唑的最低抑菌浓度（MIC）。
共识别出217例可评估发作病例，其中93.5%发生在成年患者中。96.3%（209/217）的发作病例在血培养阳性后72小时内开始使用氟康唑。89.9%（195/217）的发作病例氟康唑剂量合适，整个队列的中位治疗持续时间为14天（四分位间距8 - 21天）。全因30天死亡率为19.8%（43/217），其中37.2%（16/43）的死亡归因于念珠菌血症。分类与回归树（CART）分析确定，感染相关死亡率的氟康唑MIC靶点为≥2 mg/L，30天总体死亡率的靶点为≥4 mg/L。尽管存在显著趋势（P = 0.051），但MIC高于或低于确定靶点的发作病例总体死亡率无差异。单因素分析显示，MIC≥2 mg/L的白色念珠菌发作病例与低于该MIC靶点的病例相比，感染相关死亡率显著升高（20.6%对4.9%；P = 0.001）。该靶点仍然是感染相关死亡率的独立预测因素（比值比8.2；95%置信区间2.3 - 29.7；P = 0.001）。
我们观察到白色念珠菌血症的感染相关死亡率与氟康唑MIC升高之间存在直接关系；总体而言，数据支持欧盟CAST和修订后的CLSI氟康唑临床断点。
