University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
University of Nijmegen, Radboud University Medical Center, Department of Pharmacy, and Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands.
Antimicrob Agents Chemother. 2017 Nov 22;61(12). doi: 10.1128/AAC.01398-17. Print 2017 Dec.
The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers ( = <0.0001 and = <0.001, respectively). All isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.).
侵袭性念珠菌病(IC)在重症监护病房(ICU)的估计归因死亡率为 30%至 40%。危重病患者的生理变化可能会影响米卡芬净的分布和消除,因此可能需要调整剂量。本研究的目的是确定重症患者米卡芬净的药代动力学参数,并评估目标达标率。测量米卡芬净的血浆浓度以估计米卡芬净的药代动力学特性。确定 株的 MIC 值以评估患者的目标达标率。有 19 名疑似或确诊侵袭性念珠菌病的患者的数据可用于分析。稳态时 0 至 24 小时的浓度-时间曲线下面积(AUC)中位数为 89.6 mg·h/L(四分位距[IQR],75.4 至 113.6 mg·h/L);这显著低于健康志愿者米卡芬净 AUC 值中位数 152.0 mg·h/L(IQR,136.0 至 162.0 mg·h/L)和 134.0 mg·h/L(IQR,118.0 至 148.6 mg·h/L)( = <0.0001 和 = <0.001)。所有 株均对米卡芬净敏感,MIC 值中位数为 0.016 mg/L(IQR,0.012 至 0.023 mg/L)。AUC/MIC 比值中位数为 5684(IQR,4325 至 7578),17 名可评估的确诊侵袭性念珠菌病患者中有 3 名(17.6%)未达到 AUC/MIC 比值目标 5000。重症患者米卡芬净暴露量低于健康志愿者。ICU 人群中米卡芬净暴露量的差异可通过患者体重解释。我们的研究结果表明,体重超过 100kg、每天接受 100mg 米卡芬净的健康状况较好(序贯器官衰竭评估[SOFA]评分<10)的患者存在米卡芬净暴露不足和潜在的不充分抗真菌治疗风险。(本研究已在 ClinicalTrials.gov 注册,标识符为 NCT01716988。)