Álvarez José C, Cuervo Sonia I, Silva Edelberto, Díaz Jorge A, Jiménez Lorena L, Parra Daniel S, Gómez Julio C, Sánchez Ricardo, Cortés Jorge A
Facultad de Medicina, Universidad Nacional de Colombia, 111321 Bogotá, Colombia.
Grupo en Enfermedades Infecciosas en Cáncer y Alteraciones Hematológicas (GREICAH), Universidad Nacional de Colombia, 111321 Bogotá, Colombia.
Antibiotics (Basel). 2021 Apr 29;10(5):504. doi: 10.3390/antibiotics10050504.
Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against and , and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels.
与无恶性肿瘤或中性粒细胞减少症的患者相比，化疗引起的发热性中性粒细胞减少症（CIFN）患者的药代动力学（PK）可能会发生变化。如果治疗未针对此进行充分调整，抗生素PK的这些变化可能会给患者带来负面结果。在这项开放标签、非随机、前瞻性、观察性和描述性研究中，为血液系统肿瘤和化疗后发热性中性粒细胞减少症患者建立了头孢吡肟的PK模型。该研究在一家癌症转诊中心进行，研究参与者每8小时接受2g静脉注射剂量的头孢吡肟，输注时间为30分钟。头孢吡肟的PK可用一个二室模型很好地描述，其清除率取决于血清肌酐水平。使用蒙特卡洛模拟表明，对于MIC水平低于肠杆菌科耐药临界点的情况，每24小时持续输注6g可较好地实现PK/PD目标。根据模拟结果，无需增加头孢吡肟的每日剂量（超过每日6g）来提高目标达成概率（PTA）。对于针对[具体病原体1]和[具体病原体2]的经验性治疗方案，采用间歇给药的累积反应分数（CFR）并不理想，在这种情况下可使用持续输注来使暴露最大化。血清肌酐水平高的患者比水平低的患者更有可能达到预定义的PK/PD目标。
