University of Massachusetts Medical School, Worcester, Massachusetts, USA.
BMC Infect Dis. 2013 Jan 16;13:14. doi: 10.1186/1471-2334-13-14.
Incorporation of the solubilizing excipient, sulfobutylether-β-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) < 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function.
A total of 128 patients aged 11-93 years who had a baseline Clcr < 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups.
The groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p < 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not.
Treatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation.
伏立康唑静脉制剂中加入增溶剂磺丁基醚-β-环糊精（SBECD）后，建议肌酐清除率（Clcr）<50 mL/min 的患者谨慎使用该制剂。本研究评估了在肾功能受损患者中，与不含 SBECD 的两种其他静脉用抗真菌药物相比，静脉用伏立康唑的安全性。
从一家大学附属医院的住院医疗系统数据库中确定了 128 名年龄在 11-93 岁之间、基线 Clcr<50 mL/min 的患者；其中，55 名患者接受卡泊芬净治疗，54 名患者接受氟康唑治疗，19 名患者接受伏立康唑治疗。治疗期间血清肌酐（Scr）和 Clcr 水平的变化与基线值进行比较，并比较各组之间的变化。
除了接受氟康唑治疗的女性比例较大外，三组患者的特征相似。接受卡泊芬净治疗的患者基线 Scr 较高，但氟康唑组 Scr 的最大升高和 Clcr 的最大降低最为显著。根据 RIFLE 标准评估的急性肾损伤（AKI）在氟康唑组比卡泊芬净组更为常见（p<0.01）；伏立康唑组 AKI 的发生率与其他两组无显著差异。感染病原体是 AKI 的预测因素，而 SBECD 的制剂不是。
在肾功能受损患者中使用含 SBECD 的抗真菌药物治疗真菌感染与 AKI 无关。由于感染病原体与 AKI 相关，因此应根据病原体的敏感性而不是 IV 制剂中是否含有 SBECD 来决定使用哪种抗真菌药物。
