Petersson J, Giske C G, Eliasson E
Function Perioperative Medicine and Intensive Care, Karolinska University hospital Solna, Stockholm, Sweden.
Section of Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Acta Anaesthesiol Scand. 2016 Nov;60(10):1425-1436. doi: 10.1111/aas.12808. Epub 2016 Sep 21.
Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics.
We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively.
We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin-tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7-52.9) and 8.6 (2.7-30.3); and for meropenem, 7.5 (4.7-10.2) and 2.4 (1.0-3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half-life was similar for eGFR and CrCl.
With standard doses of meropenem and piperacillin-tazobactam, plasma concentrations in ICU patients vary > 10-fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.
在使用β-内酰胺类抗生素治疗重症监护患者时，关于最佳剂量以及是否需要进行血药浓度监测仍存在争议。
我们研究了接受这两种抗生素治疗的重症监护病房患者，但排除了接受肾脏替代治疗的患者。在给药间隔的中期和末期测量抗生素浓度，可行时在2至3天后重复测量。根据血肌酐和胱抑素C估算肾小球滤过率（GFR），根据胱抑素C计算GFR（eGFR）并测量肌酐清除率（CrCl）。将测量浓度与铜绿假单胞菌的临床敏感断点进行比较，哌拉西林和美罗培南的断点分别为16和2mg/l。
我们分别分析了20例接受哌拉西林-他唑巴坦治疗和19例接受美罗培南治疗患者的33对和31对样本。给药间隔中期和末期的抗生素浓度，哌拉西林分别为27.0（14.7 - 52.9）和8.6（2.7 - 30.3）；美罗培南分别为7.5（4.7 - 10.2）和2.4（1.0 - 3.5）。所有数值均为中位数（四分位间距），单位为mg/l。给药间隔中期和末期低于断点的测量浓度百分比，哌拉西林分别为27%和61%；美罗培南分别为6%和48%。较低的GFR估算值与较高的浓度相关，但在GFR相似的患者中浓度差异很大。eGFR和CrCl与终末浓度半衰期的相关性相似。
使用标准剂量的美罗培南和哌拉西林-他唑巴坦时，重症监护病房患者的血浆浓度变化超过10倍，且相当比例患者的血药浓度未达最佳。肾功能相似的患者之间差异也很大。
