Finazzi Stefano, Luci Giacomo, Olivieri Carlo, Langer Martin, Mandelli Giulia, Corona Alberto, Viaggi Bruno, Di Paolo Antonello
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24020 Ranica, Italy.
Associazione GiViTI, c/o Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
Antibiotics (Basel). 2022 Aug 29;11(9):1164. doi: 10.3390/antibiotics11091164.
The challenging severity of some infections, especially in critically ill patients, makes the diffusion of antimicrobial drugs within tissues one of the cornerstones of chemotherapy. The knowledge of how antibacterial agents penetrate tissues may come from different sources: preclinical studies in animal models, phase I-III clinical trials and post-registration studies. However, the particular physiopathology of critically ill patients may significantly alter drug pharmacokinetics. Indeed, changes in interstitial volumes (the ) and/or in glomerular filtration ratio may influence the achievement of bactericidal concentrations in peripheral compartments, while inflammation can alter the systemic distribution of some drugs. On the contrary, other antibacterial agents may reach high and effective concentrations thanks to the increased tissue accumulation of macrophages and neutrophils. Therefore, the present review explores the tissue distribution of beta-lactams and other antimicrobials acting on the cell wall and cytoplasmic membrane of bacteria in critically ill patients. A systematic search of articles was performed according to PRISMA guidelines, and tissue/plasma penetration ratios were collected. Results showed a highly variable passage of drugs within tissues, while large interindividual variability may represent a hurdle which must be overcome to achieve therapeutic concentrations in some compartments. To solve that issue, off-label dosing regimens could represent an effective solution in particular conditions.
某些感染的严重程度颇具挑战性，尤其是在重症患者中，这使得抗菌药物在组织内的扩散成为化疗的基石之一。关于抗菌药物如何穿透组织的知识可能来自不同来源：动物模型的临床前研究、I - III期临床试验以及注册后研究。然而，重症患者的特殊病理生理学可能会显著改变药物的药代动力学。确实，间质容积（）和/或肾小球滤过率的变化可能会影响外周隔室中杀菌浓度的达到，而炎症会改变某些药物的全身分布。相反，由于巨噬细胞和中性粒细胞在组织中的积累增加，其他抗菌药物可能会达到高浓度且有效的浓度。因此，本综述探讨了重症患者中β - 内酰胺类药物以及其他作用于细菌细胞壁和细胞质膜的抗菌药物的组织分布。根据PRISMA指南对文章进行了系统检索，并收集了组织/血浆数据。结果显示药物在组织内的通透率高度可变，而个体间的巨大差异可能是在某些隔室中达到治疗浓度必须克服的障碍。为了解决这个问题，在特定情况下，超说明书给药方案可能是一种有效的解决方案。
