背景:β-内酰胺抗生素(βLA)是重症监护病房(ICU)中最常用的抗生素。ICU患者表现出许多导致药代动力学(PK)和药效学(PD)特异性的病理生理特征,导致剂量不足的风险。法国药理学与治疗学学会(SFPT)和法国麻醉与重症监护医学学会(SFAR)已联手为ICU患者提供优化β-内酰胺治疗的指南。
方法:由来自两个学会的18名专家组成的共识委员会的使命是制定这些指南。整个过程独立于任何行业资金进行。根据PICO模型制定的问题清单(人口,干预,比较,和结果)是由专家起草的。然后,两位书目专家根据PRISMA建议使用预定义的关键词分析了自2000年1月以来发表的文献。使用GRADE®方法评估从文献中鉴定的数据的质量。由于缺乏以死亡率为主要判断标准的有力研究,决定了,在起草建议之前,仅制定“可选”建议。
结果:经过两轮评级和一次修订,SFPT-SFAR指南小组就21个可选建议和涵盖四个领域的护理概论算法达成了强有力的一致:(i)药代动力学变异性,(二)PK-PD关系,(iii)管理方式,和(iv)治疗药物监测(TDM)。关于ICU患者中βLA给药的最重要建议涉及(i)考虑该人群中PK变异性的许多来源;(ii)将100%给药间隔内致病菌最小抑制浓度(MIC)的4至8倍的游离血浆浓度定义为PK-PD目标,以最大程度地提高细菌学和临床反应;(iii)在最严重的患者中使用连续或长期给药βLA,在高MIC细菌的情况下和在下呼吸道感染的情况下提高临床治愈;和(iv)使用TDM提高PK-PD目标的实现。
结论:专家强烈建议使用个性化给药,在危重患者中施用βLA时,连续或长时间输注和治疗药物监测。
BACKGROUND: Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide
guidelines on the optimization of beta-lactam treatment in ICU patients.
METHODS: A
consensus committee of 18 experts from the two societies had the mission of producing these
guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only \"optional\" recommendations.
RESULTS: After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR
guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement.
CONCLUSIONS: The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients.