Jongmans C, Muller A E, Van Den Broek P, Cruz De Almeida B De Melo, Van Den Berg C, Van Oldenrijk J, Bos P K, Koch B C P
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands.
Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, Netherlands.
Front Pharmacol. 2022 Jun 28;13:900551. doi: 10.3389/fphar.2022.900551. eCollection 2022.
Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding. A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: "protein binding," "beta-lactam antibiotic," and "body fluid." Only studies were included where protein binding was measured in humans . The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding. Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients. PROSPERO, identifier (CRD42021252776).
蛋白质结合可降低β-内酰胺类抗生素的药理作用。只有游离部分具有抗菌作用。本系统文献综述的目的是概述目前关于头孢菌素在人体体液中蛋白质结合的知识，并描述影响蛋白质结合水平的患者特征。在Embase、Medline ALL、Web of Science核心合集和Cochrane对照试验中央注册库中进行了系统的文献检索，检索词如下：“蛋白质结合”、“β-内酰胺类抗生素”和“体液”。仅纳入了在人体中测量蛋白质结合的研究。大多数报告蛋白质结合情况的研究是在血清或血浆中进行的。其他体液包括心包液、水疱液、支气管分泌物、胸腔渗出液、伤口渗出液、脑脊液、透析液和腹膜液。不同头孢菌素之间以及不同患者类别之间的蛋白质结合情况有所不同。对于头孢唑林、头孢曲松、头孢匹胺和头孢尼西，描述了血清或血浆中蛋白质结合的非线性模式。一些患者特征与血清白蛋白浓度低有关，并且与健康志愿者相比，这些患者的蛋白质结合较低。这些患者包括危重症患者、透析患者以及手术期间接受体外循环的患者。虽然这些患者组中蛋白质结合的平均/中位数百分比较低，但个体值可能有很大差异。年龄本身不太可能影响蛋白质结合，然而有限的数据表明新生儿的蛋白质结合较低。肥胖与蛋白质结合改变无关。由于数据稀缺，无法得出关于血液以外其他体液中蛋白质结合的结论。在血清和血浆中，每种头孢菌素以及不同患者类别之间的蛋白质结合存在很大差异。确定了几个导致蛋白质结合较低的特征。一些头孢菌素显示出非线性蛋白质结合模式这一发现使得预测个体患者的游离浓度更加困难。综合所有这些因素，建议测量游离浓度以优化个体患者的抗生素暴露。PROSPERO，标识符（CRD42021252776）。
