Lodl Emma F, Alshaer Mohammad H, Adams C Brooke, Richards Ashley, Peloquin Charles, Venugopalan Veena
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
University of Florida College of Pharmacy, Gainesville, FL, USA.
J Oncol Pharm Pract. 2024 Oct;30(7):1207-1213. doi: 10.1177/10781552231213883. Epub 2023 Nov 19.
Cefepime is a fourth-generation cephalosporin and is a workhorse for the empiric treatment of febrile neutropenia (FN). Beta-lactam therapeutic drug monitoring (TDM) has emerged as a dose optimization strategy in patient populations with altered kinetics. Prior literature has demonstrated that patients with FN exhibit augmented renal clearance which may lead to subtherapeutic drug concentrations with standard dosing regimens. The aim of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) target attainment and clinical outcomes in patients with hematologic malignancies and FN who were treated empirically with cefepime.
This was a prospective, single-center study of adults with hematologic malignancies and FN admitted to the inpatient unit. The primary outcome was PK/PD target attainment (defined as 100% free time greater than minimum inhibitory concentration (100% T > MIC)). Secondary clinical outcomes were time to defervescence, time to ANC recovery, in-hospital mortality, and cefepime failure.
There were 55 patients in our study. Forty-three (78%) patients achieved the primary outcome of PK/PD target attainment. The mean time to defervescence was similar between those that achieved PK/PD target attainment and those that did not (95% CI -0.75 to 1.25, p = 0.62).
This study showed that standard cefepime dosing in patients with hematologic malignancies and FN does not result in achievement of 100% T > MIC in all patients. Patients in the group that did not achieve PK/PD target attainment were younger with increased creatinine clearance, indicating that cefepime TDM may be especially beneficial in these patients.
头孢吡肟是一种第四代头孢菌素，是经验性治疗发热性中性粒细胞减少症（FN）的常用药物。β-内酰胺类治疗药物监测（TDM）已成为一种针对药代动力学改变患者群体的剂量优化策略。既往文献表明，FN患者的肾脏清除率增加，这可能导致标准给药方案下药物浓度低于治疗水平。本研究的目的是评估接受头孢吡肟经验性治疗的血液系统恶性肿瘤合并FN患者的药代动力学/药效学（PK/PD）目标达成情况及临床结局。
这是一项针对入住住院病房的血液系统恶性肿瘤合并FN成年患者的前瞻性单中心研究。主要结局是PK/PD目标达成情况（定义为游离时间大于最低抑菌浓度的百分比达到100%（100%T＞MIC））。次要临床结局包括退热时间、中性粒细胞绝对值（ANC）恢复时间、住院死亡率和头孢吡肟治疗失败情况。
我们的研究中有55例患者。43例（78%）患者实现了PK/PD目标达成的主要结局。实现PK/PD目标达成的患者与未达成的患者之间的平均退热时间相似（95%CI -0.75至1.25，p = 0.62）。
本研究表明，血液系统恶性肿瘤合并FN患者使用标准剂量的头孢吡肟并不能使所有患者达到100%T＞MIC。未实现PK/PD目标达成的患者年龄较小，肌酐清除率较高，这表明头孢吡肟TDM可能对这些患者特别有益。
