Pharmacokinetic parameters of CAZ–AVI in the normal lung and in models of pneumonia: lessons for treatment optimization in critical care

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to β-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-β-lactam β-lactamase inhibitor avibactam, which exhibits broad-spectrum β-lactamase inhibition in vitro, are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.