Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Nancy, Vandœuvre-Lès-Nancy, F-54511, France.
University of Lorraine, F-54000, Nancy, France.
J Antimicrob Chemother. 2020 Jan 1;75(1):156-161. doi: 10.1093/jac/dkz407.
Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage.
To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes.
This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum β-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606).
Forty-eight patients were included with a median (IQR) age of 64 (53-74) years and a SAPS II of 40 (32-65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered β-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64-0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target.
In severe IAIs, high doses of β-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal β-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.
需要手术的重症腹腔内感染（IAI）的危重症患者可能经历多种药代动力学（PK）改变，这可能导致β-内酰胺类药物剂量不足。
测量高剂量和最佳给药方案后β-内酰胺类药物的血清和腹腔渗出液浓度。
这项观察性前瞻性研究纳入了怀疑患有 IAI 且需要手术和β-内酰胺类抗生素作为经验性治疗的危重症患者。在手术期间和 24 小时稳态期后测量血清和腹腔渗出液浓度。PK/药效动力学（PD）目标是在获得细菌学证据（先验）之前，根据最坏情况（基于欧盟药敏委员会最高流行病学折点值）获得血清β-内酰胺类药物浓度为 100% fT>4×MIC，然后在确定分离细菌的 MIC 后重新定义（后验）。在 ClinicalTrials.gov 注册（NCT03310606）。
共纳入 48 例患者，中位（IQR）年龄为 64（53-74）岁，SAPS II 为 40（32-65）。主要诊断为继发性医院获得性腹膜炎。哌拉西林/他唑巴坦是最常用的β-内酰胺类抗生素（75%）。24 小时稳态期后，血清/腹腔哌拉西林/他唑巴坦比值为 0.88（0.64-0.97）。在获得细菌学证据之前，16 例患者（33.3%）达到了先验 PK/PD 目标。34 例患者（71%）可获得微生物鉴定结果。根据分离细菌的 MIC，78%的患者达到了血清 PK/PD 目标。
在严重的 IAI 中，高剂量的β-内酰胺类药物可确保 78%的严重 IAI 危重症患者在最初 24 小时内血清中 100% fT>4×MIC。为了确定最佳β-内酰胺类药物剂量，PK/PD 目标应考虑组织穿透率和局部生态。
