Luque Sonia, Benítez-Cano Adela, Larrañaga Leire, Sorlí Luisa, Navarrete María Eugenia, Campillo Nuria, Carazo Jesús, Ramos Isabel, Adalia Ramón, Grau Santiago
Department of Pharmacy, Hospital del Mar, IMIM (Hospital del Mar Research Institute), Universitat Autonoma de Barcelona, 08003 Barcelona, Spain.
Department of Anaesthesiology and Surgical Intensive Care, Hospital del Mar, IMIM (Hospital del Mar Research Institute), 08003 Barcelona, Spain.
Antibiotics (Basel). 2021 Jun 3;10(6):666. doi: 10.3390/antibiotics10060666.
: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body weight (LwBW) and therefore information is lacking on the most appropriate dosing regimens, especially when administered by extended infusion. : To assess if the current administered doses of meropenem could lead to supratherapeutic concentrations in LwBW patients and to identify the factors independently associated with overexposure. Methods: A matched case-control 1:1 study of surgical critically ill patients treated with meropenem administered by extended or continuous infusion and undergoing therapeutic drug monitoring was conducted. Cases (patients with LwBW (body mass index (BMI) < 18.5 kg/m)) were matched with normal body weight controls (NBW) (patients with BMI ≥ 18.5 kg/m and ≤30 kg/m)) by age, gender, baseline renal function and severity status (APACHE II score). A 100% fT > MIC was considered an optimal pharmacokinetic/pharmacodynamic (PK/PD) target and 100% fT > 10 × MIC as supratherapeutic exposure. : Thirty-six patients (18 cases and 18 controls) were included (median (range) age, 57.5 (26-75) years; 20 (55.6% male)). Meropenem was administered by 6 h (extended) or 8 h (continuous) infusion at a median (range) daily dose of 5 (1-6) g/day. Similar median meropenem trough plasma concentrations (Cmin,ss), measured pre-dose on day three to four of treatment) were observed in the two groups (19.9 (22.2) mg/L vs 22.4 (25.8) mg/L, > 0.999). No differences in the proportion of patients with an optimal or a supratherapeutic PKPD target between cases and controls were observed. A baseline estimated glomerular filtration rate (eGFR) < 90 mL/min was the only factor independently associated with a supratherapeutic PK/PD target. : LwBW seems not to be a risk factor for achieving a supratherapeutic PK/PD target in critically ill patients receiving meropenem at standard doses by extended or continuous infusion.
严重感染的危重症患者出现的病理生理变化，如体重极端异常，可能会改变抗菌药物的药代动力学（PK），导致治疗失败或毒性反应。对于低体重（LwBW）的危重症患者，几乎没有美罗培南的药代动力学数据，因此缺乏关于最合适给药方案的信息，尤其是在延长输注给药时。：评估当前美罗培南给药剂量是否会导致LwBW患者出现超治疗浓度，并确定与药物过度暴露独立相关的因素。方法：进行一项1:1匹配病例对照研究，研究对象为接受美罗培南延长或持续输注治疗并进行治疗药物监测的外科危重症患者。病例（LwBW患者（体重指数（BMI）<18.5 kg/m²））与正常体重对照（NBW）（BMI≥18.5 kg/m²且≤30 kg/m²的患者）按年龄、性别、基线肾功能和严重程度状态（急性生理与慢性健康状况评分系统II（APACHE II）评分）进行匹配。100%的fT>MIC被认为是最佳药代动力学/药效学（PK/PD）目标，100%的fT>10×MIC被视为超治疗暴露。：纳入36例患者（18例病例和18例对照）（年龄中位数（范围）为57.5（26 - 75）岁；20例（55.6%）为男性）。美罗培南通过6小时（延长）或8小时（持续）输注给药，日剂量中位数（范围）为5（1 - 6）g/天。两组在治疗第3至4天给药前测得的美罗培南谷浓度（Cmin,ss）中位数相似（19.9（22.2）mg/L对22.4（25.8）mg/L，P>0.999）。病例组和对照组之间在达到最佳或超治疗PKPD目标的患者比例上未观察到差异。基线估计肾小球滤过率（eGFR）<90 mL/min是与超治疗PK/PD目标独立相关的唯一因素。：对于通过延长或持续输注接受标准剂量美罗培南治疗的危重症患者，LwBW似乎不是实现超治疗PK/PD目标的危险因素。
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