Burns Trauma and Critical Care Research Centre, University of Queensland.
Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14.
Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.
This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.
We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.
Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
感染导致的危重症患者的发病率和死亡率仍是一个全球性的医疗保健问题。我们旨在确定危重症患者β-内酰胺类抗生素的给药剂量是否能达到与最大活性相关的浓度，以及抗生素浓度是否会影响患者的预后。
这是一项前瞻性、多国家的药代动力学点患病率研究，包括 8 种β-内酰胺类抗生素。每位患者在单个给药间隔内采集 2 份血样。主要的药代动力学/药效学目标是病原体最低抑菌浓度（MIC）的 50%（50%fT>MIC）和 100%（100%fT>MIC）的游离抗生素浓度。我们使用偏态逻辑回归来描述抗生素暴露对患者预后的影响。
我们共纳入了 384 名患者（361 名可评估患者），来自 68 家医院。中位年龄为 61 岁（四分位距[IQR]，48-73），急性生理学和慢性健康评估 II 评分中位数为 18 分（IQR，14-24），65%的患者为男性。在 248 名接受感染治疗的患者中，有 16%未达到 50%fT>MIC，这些患者的临床转归阳性的可能性降低了 32%（比值比[OR]，0.68；P =.009）。临床转归阳性与 50%fT>MIC 和 100%fT>MIC 比值的增加相关（OR 分别为 1.02 和 1.56；P <.03），与疾病严重程度状态存在显著交互作用。
感染的危重症患者可能由于抗生素暴露不足而导致不良结局；为了改善这些病情最严重的患者的预后，可能需要对更个体化的抗生素剂量进行范式转变。
