Infectious Diseases Institute, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel.
Internal Medicine Department D, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel.
Eur J Clin Microbiol Infect Dis. 2019 Sep;38(9):1773-1780. doi: 10.1007/s10096-019-03611-1. Epub 2019 Jun 13.
To evaluate the association between fluconazole exposure parameters and clinical outcomes in patients with candidemia. We retrospectively included all adults with candidemia in a single center from January 2009 to December 2017, treated initially with fluconazole for fluconazole-susceptible candidemia. We assessed the association between fluconazole exposure parameters and 30-day mortality or 14-day clinical failure, a composite of mortality at day 14 or persistent candidemia ≥ 72 h, in all patients and in patients with C. glabrata candidemia. During the study period, 158 patients fulfilled the inclusion criteria. Main species were C. albicans 66 (41.8%), C. glabrata 35 (22.2%), and C. parapsilosis 31 (19.6%). Sixty patients (38%) died within 30 days. Sixty-one patients (38.6%) experienced 14-day failure. In 30-day survivors, the median AUC/MIC was 2279 [398, 5989] versus 1764 [238, 6714] h in non-survivors, p = 0.75. Median fluconazole MIC was 0.75 [0.25, 4] and 1 [0.22, 5.50] mg/L, p = 0.54, respectively. Similar non-significant differences were found for other fluconazole exposure parameters and in the 14-day clinical failure analysis. For C. glabrata, a higher AUC/MIC was observed among 30-day survivors with a median of 230 [77, 539] compared to 96 [75, 164] h in non-survivors, p = 0.008, in parallel with a trend for lower MIC values (median 7 [1, 2] versus 16 [8, 24] mg/L, p = 0.06, respectively). Currently used fluconazole dosing has no association with clinical outcome in Candida with low MIC values. For Candida species with high MICs, attention to dosing is needed.
评估氟康唑暴露参数与念珠菌血症患者临床结局之间的关联。我们回顾性纳入了 2009 年 1 月至 2017 年 12 月在单一中心接受氟康唑治疗的所有成人念珠菌血症患者,这些患者对氟康唑敏感。我们评估了氟康唑暴露参数与 30 天死亡率或 14 天临床失败(死亡率在第 14 天或持续念珠菌血症≥72 小时的复合终点)之间的关系,评估对象为所有患者以及克柔念珠菌血症患者。研究期间,共纳入 158 例患者。主要菌种为白色念珠菌 66 株(41.8%)、光滑念珠菌 35 株(22.2%)和近平滑念珠菌 31 株(19.6%)。30 天内死亡 60 例(38%),14 天内失败 61 例(38.6%)。在 30 天幸存者中,AUC/MIC 中位数为 2279[398,5989] h,而非幸存者为 1764[238,6714] h,p=0.75。氟康唑 MIC 中位数分别为 0.75[0.25,4] 和 1[0.22,5.50]mg/L,p=0.54。其他氟康唑暴露参数和 14 天临床失败分析也未发现有统计学意义的差异。对于克柔念珠菌,30 天幸存者的 AUC/MIC 中位数为 230[77,539] h,而非幸存者为 96[75,164] h,p=0.008,同时 MIC 值也呈下降趋势(中位数分别为 7[1,2] 和 16[8,24]mg/L,p=0.06)。目前使用的氟康唑剂量与 MIC 值较低的念珠菌临床结局无关。对于 MIC 值较高的念珠菌,需要注意剂量。