Department of Intensive and Perioperative Care, Skåne University Hospital, Malmö, Sweden.
Department of Infectious Diseases, Skåne University Hospital, Malmö, Sweden.
Acta Anaesthesiol Scand. 2024 Apr;68(4):530-537. doi: 10.1111/aas.14382. Epub 2024 Feb 26.
Antibiotic concentration target attainment is known to be poor in critically ill patients. Dose adjustment is recommended in patients with altered clearance, obesity and those with bacterial species with intermediate susceptibility. The aim of this study was to investigate the variation of antibiotic concentration in critically ill patients with standard or adjusted dosing regimens.
The concentration of three beta-lactam antibiotics used in the intensive care unit (ICU) setting, cefotaxime, piperacillin/tazobactam, and meropenem, was measured in patients with confirmed or suspected infection. Mid-dose and trough values were collected during a single dosing interval. The pharmacokinetic endpoints were a free antibiotic concentration that, during the whole dosing interval, was above MIC (100% ƒT > MIC, primary endpoint) or above four times MIC (100% ƒT > 4MIC, secondary endpoint). Non-species related MIC breakpoints were used (1 mg/L for cefotaxime, 8 mg/L for piperacillin/tazobactam, and 2 mg/L for meropenem).
We included 102 patients (38 cefotaxime, 30 piperacillin/tazobactam, and 34 meropenem) at a single ICU, with a median age of 66 years. In total, 73% were males, 40% were obese (BMI ≥30) and the median SAPS 3 score was 63 points. Of all patients, 78 patients (76%) reached the primary endpoint (100%ƒT > MIC), with 74% for cefotaxime, 67% for piperacillin/tazobactam and 88% for meropenem. Target attainment for 100% ƒT > 4MIC was achieved in 40 (39%) patients, overall, with 34% for cefotaxime, 30% for piperacillin/tazobactam and 53% for meropenem. In patients with standard dose 71% attained 100%ƒT > MIC and 37% for 100%ƒT > 4MIC. All patients with reduced dose attained 100%ƒT > MIC and 27% attained 100% ƒT > 4MIC. In patients with increased dose 79% attained 100%ƒT > MIC and 48% 100%ƒT > 4MIC respectively.
Beta-lactam antibiotics concentration vary widely in critically ill patients. The current standard dosing regimens employed during the study were not sufficient to reach 100% ƒT > MIC in approximately a quarter of the patients. In patients where dose adjustment was performed, the group with increased dose also had low target attainment, as opposed to patients with dose reduction, who all reached target. This suggests the need for further individualization of dosing where therapeutic drug monitoring can be an alternative to further increase target attainment.
在危重症患者中，抗生素浓度目标达标情况不佳是已知的。建议在清除率改变、肥胖和具有中间敏感性的细菌物种的患者中调整剂量。本研究的目的是调查在使用标准或调整剂量方案的危重症患者中抗生素浓度的变化。
在 ICU 环境中使用的三种β-内酰胺类抗生素（头孢噻肟、哌拉西林/他唑巴坦和美罗培南）的浓度在确诊或疑似感染的患者中进行了测量。在单次给药间隔期间采集中剂量和谷值。药代动力学终点是在整个给药间隔内游离抗生素浓度超过 MIC（100%ƒT> MIC，主要终点）或超过 4 倍 MIC（100%ƒT> 4MIC，次要终点）。使用非物种相关的 MIC 断点（头孢噻肟 1mg/L、哌拉西林/他唑巴坦 8mg/L 和美罗培南 2mg/L）。
我们在一家 ICU 中纳入了 102 名患者（38 名头孢噻肟、30 名哌拉西林/他唑巴坦和 34 名美罗培南），中位年龄为 66 岁。总共 73%为男性，40%为肥胖（BMI≥30），SAPS 3 评分中位数为 63 分。所有患者中，78 名（76%）达到了主要终点（100%ƒT> MIC），头孢噻肟为 74%，哌拉西林/他唑巴坦为 67%，美罗培南为 88%。达到 100%ƒT> 4MIC 的目标的患者有 40 名（39%），其中头孢噻肟为 34%，哌拉西林/他唑巴坦为 30%，美罗培南为 53%。在接受标准剂量的患者中，71%达到 100%ƒT> MIC，37%达到 100%ƒT> 4MIC。所有接受减少剂量的患者均达到 100%ƒT> MIC，27%达到 100%ƒT> 4MIC。在接受增加剂量的患者中，79%达到 100%ƒT> MIC，48%达到 100%ƒT> 4MIC。
β-内酰胺类抗生素在危重症患者中的浓度差异很大。在研究期间使用的当前标准剂量方案，约四分之一的患者无法达到 100%ƒT> MIC。在进行剂量调整的患者中，增加剂量组的目标达标率也较低，而剂量减少组的患者则全部达到了目标。这表明需要进一步个体化给药，治疗药物监测可以作为进一步提高目标达标率的替代方法。
