Viaggi Bruno, Cangialosi Alice, Langer Martin, Olivieri Carlo, Gori Andrea, Corona Alberto, Finazzi Stefano, Di Paolo Antonello
Department of Anesthesiology, Neuro-Intensive Care Unit, Careggi University Hospital, 50139 Florence, Italy.
Associazione GiViTI, c/o Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
Antibiotics (Basel). 2022 Sep 3;11(9):1193. doi: 10.3390/antibiotics11091193.
In patients that are admitted to intensive care units (ICUs), the clinical outcome of severe infections depends on several factors, as well as the early administration of chemotherapies and comorbidities. Antimicrobials may be used in off-label regimens to maximize the probability of therapeutic concentrations within infected tissues and to prevent the selection of resistant clones. Interestingly, the literature clearly shows that the rate of tissue penetration is variable among antibacterial drugs, and the correlation between plasma and tissue concentrations may be inconstant. The present review harvests data about tissue penetration of antibacterial drugs in ICU patients, limiting the search to those drugs that mainly act as protein synthesis inhibitors and disrupting DNA structure and function. As expected, fluoroquinolones, macrolides, linezolid, and tigecycline have an excellent diffusion into epithelial lining fluid. That high penetration is fundamental for the therapy of ventilator and healthcare-associated pneumonia. Some drugs also display a high penetration rate within cerebrospinal fluid, while other agents diffuse into the skin and soft tissues. Further studies are needed to improve our knowledge about drug tissue penetration, especially in the presence of factors that may affect drug pharmacokinetics.
在入住重症监护病房（ICU）的患者中，严重感染的临床结局取决于多种因素，以及化疗的早期应用和合并症。抗菌药物可能会用于超说明书用药方案，以最大限度地提高感染组织内达到治疗浓度的概率，并防止耐药克隆的产生。有趣的是，文献清楚地表明，抗菌药物的组织穿透率各不相同，血浆浓度与组织浓度之间的相关性可能并不恒定。本综述收集了关于ICU患者抗菌药物组织穿透情况的数据，将检索范围限制在主要作为蛋白质合成抑制剂以及破坏DNA结构和功能的药物。不出所料，氟喹诺酮类、大环内酯类、利奈唑胺和替加环素在上皮衬液中具有良好的扩散性。这种高穿透性对于呼吸机相关性肺炎和医疗保健相关肺炎的治疗至关重要。一些药物在脑脊液中的穿透率也很高，而其他药物则可扩散到皮肤和软组织中。需要进一步研究以增进我们对药物组织穿透的了解，尤其是在存在可能影响药物药代动力学的因素的情况下。
