Clinical Appraisal of Cefiderocol in the Treatment of Non-fermenting Gram-Negative Bacilli

Abstract

Purpose of Review: Cefiderocol has a potential role in the treatment of infections caused by increasingly resistant non-fermenting Gram-negative organisms. Recent Findings: Non-fermenting Gram-negative organisms pose a unique threat to public health given their arsenal of inherent resistance mechanisms. High rates of intrinsic resistance to a wide array of agents, inducible adaptive resistance, and the ability to acquire resistance through horizontal transfer of resistance genes limit the utility of conventional antimicrobial treatment options against non-fermenting Gram-negative infections. Beta-lactams, one of the most reliable classes of antimicrobials, are often rendered inactive by the acquisition of beta-lactamases, with activity potentially restored by beta-lactamase inhibitors. Alteration of intrinsic mechanisms of resistance, porin channels, and efflux pumps reduce the ability of beta-lactamase inhibitors to protect the activity of beta-lactams. This multifactorial nature of resistance exhibited by non-fermenting Gram-negative organisms is difficult to overcome and novel agents are needed to combat this growing threat. Summary: Cefiderocol is a novel siderophore cephalosporin that utilizes the active transport of ferric iron to gain access to the periplasmic space of Gram-negative organisms. Cefiderocol also has additional modifications that confer some stability in the presence of beta-lactamases, which can be particularly beneficial for infections caused by non-fermenters. Herein, we discuss the potential role of cefiderocol therapy in the management of infections caused by non-fermenting Gram-negative bacilli, with an intentional focus on carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa, and Stenotrophomonas spp.