Alraish Rawan, Wicha Sebastian G, Frey Otto R, Roehr Anka C, Pratschke Johann, Stockmann Martin, Wuensch Tilo, Kaffarnik Magnus
Department of Surgery, Campus Charité Mitte/Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, 20146 Hamburg, Germany.
Technol Health Care. 2022;30(2):309-321. doi: 10.3233/THC-191847.
Critically ill patients commonly suffer from infections that require antimicrobial therapy. In previous studies, liver dysfunction was shown to have an essential impact on the dose selection in these patients. This pilot study aims to assess the influence of liver dysfunction, measured by the novel LiMAx test, on clinical outcomes in critically ill patients treated with linezolid.
Twenty-nine critically ill patients were included and treated with linezolid. Indications for linezolid therapy were secondary or tertiary peritonitis (46.7%), bloodstream infection (6.7%) and 46.7% were other infections with gram-positive bacteria. Linezolid Cmin, maximal liver function capacity (LiMAx test) and plasma samples were collected while linezolid therapy was in a steady-state condition. Furthermore, potential factors for the clinical outcome were investigated using logistic regression analysis. Clinical cure was defined as the resolution or significant improvement of clinical symptoms without using additional antibiotic therapy or intervention.
Cured patients presented lower median linezolid Cmin yet a significantly higher mean LiMAx-value compared to the clinical failure group (1.9 mg/L vs. 5.1 mg/L) (349 μg/kg/h vs. 131 μg/kg/h). In the logistic regression model, LiMAx < 178 μg/kg/h was the only independent predictor of clinical failure with a sensitivity of 77% and specificity of 93%.
The LiMAx test predicts clinical failure more precisely than linezolid trough levels in critically ill surgical patients. Therefore liver failure may have a stronger impact on the outcome of critically ill surgical patients than low linezolid Cmin. While linezolid Cmin failed to predict patient's outcome, LiMAx results were the only independent predictor of clinical failure.
重症患者常遭受需要抗菌治疗的感染。在先前的研究中,肝功能障碍对这些患者的剂量选择有重要影响。这项前瞻性研究旨在评估通过新型LiMAx试验测定的肝功能障碍对接受利奈唑胺治疗的重症患者临床结局的影响。
纳入29例重症患者并给予利奈唑胺治疗。利奈唑胺治疗的适应证为继发性或三发性腹膜炎(46.7%)、血流感染(6.7%),46.7%为其他革兰阳性菌感染。在利奈唑胺治疗处于稳态时收集利奈唑胺谷浓度(Cmin)、最大肝功能容量(LiMAx试验)和血浆样本。此外,使用逻辑回归分析研究临床结局的潜在因素。临床治愈定义为在未使用额外抗生素治疗或干预的情况下临床症状缓解或显著改善。
与临床治疗失败组相比,治愈患者的利奈唑胺Cmin中位数较低,但平均LiMAx值显著较高(1.9 mg/L对5.1 mg/L)(349 μg/kg/h对131 μg/kg/h)。在逻辑回归模型中,LiMAx<178 μg/kg/h是临床治疗失败的唯一独立预测因素,敏感性为77%,特异性为93%。
在重症外科患者中,LiMAx试验比利奈唑胺谷浓度更能准确预测临床治疗失败。因此,肝功能衰竭对重症外科患者结局的影响可能比利奈唑胺低Cmin更强。虽然利奈唑胺Cmin未能预测患者结局,但LiMAx结果是临床治疗失败的唯一独立预测因素。