Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review-Part II

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.

Automated summary

The clinical outcome of severe infections in ICU patients depends on multiple factors, including early administration of chemotherapies and comorbidities. Different antibacterial drugs have variable tissue penetration rates, and the correlation between plasma and tissue concentrations may be inconsistent. This review focuses on antibacterial drugs that act as protein synthesis inhibitors and disrupt DNA structure and function. It found that fluoroquinolones, macrolides, linezolid, and tigecycline have excellent diffusion into epithelial lining fluid, which is crucial for the treatment of ventilator and healthcare-associated pneumonia. Some drugs also show high penetration rates in cerebrospinal fluid, skin, and soft tissues. Further studies are needed to improve understanding of drug tissue penetration, especially in the presence of factors that may affect drug pharmacokinetics.