Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review—Part I

Abstract

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 third space) 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.

Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine

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Pharmacokinetics of SPR206 in Plasma, Pulmonary Epithelial Lining Fluid, and Alveolar Macrophages following Intravenous Administration to Healthy Adult Subjects

“…Intrapulmonary concentrations of systemically administered antibiotics that exceed the MIC of target pathogens are important to achieve successful treatment outcomes from serious infections of the respiratory tract, especially those patients with pneumonia and in critical care units ( 37 , 41 – 43 ). Beta-lactams, fluoroquinolones, macrolides, linezolid, and tigecycline demonstrate good penetration following oral or parenteral administration ( 41 , 43 , 44 ).…”

Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland—What Are They Susceptible to?

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