Cefiderocol for Carbapenem-Resistant Bacteria: Handle with Care! A Review of the Real-World Evidence

Abstract

(1) Background: healthcare-associated infections are one of the most frequent adverse events in healthcare delivery worldwide. Several antibiotic resistance mechanisms have been developed, including those to carbapenemase. Cefiderocol (CFD) is a novel siderophore cephalosporin designed to treat carbapenem-resistant bacteria. (2) Methods: we performed a systematic review of all cases reported in the literature to outline the existing evidence. We evaluated real-world evidence studies of CFD in the treatment of carbapenem-resistant (CR) bacteria. (3) Results: a total of 19 publications treating cases of infection by CR bacteria were included. The three most frequent CR pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. A regimen of 2 g every 8 h was most frequently adopted for CFD with a mean treatment duration of 25.6 days. CFD was generally well tolerated, with fewer side effects. The success rate of CFD therapy was satisfactory and almost 70% of patients showed clinical recovery; of these, nearly half showed negative blood cultures and infection-free status. (4) Conclusions: This review indicates that CFD is active against important GN organisms including Enterobacteriaceae, P. aeruginosa, and A. baumannii. CFD seems to have a safe profile.

Next-Generation Sequencing of Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated from Patients Hospitalized in the University Hospital Facilities

“…While we could rely on the improved efficacy of other more current antibacterial agents [ 28 , 29 ] or maybe some natural substances [ 30 ] and their derivatives that are expected in our healthcare facilities, we cannot conclude that the resistance of CR K. pneumoniae strains will not increase over time.…”

Novel Antimicrobial Agents for Gram-Negative Pathogens

“…Real-world data on CEFID use for carbapenem-resistant pathogens have recently been published [ 59 ]. The authors reported on 172 individuals, including the CREDIBLE-CR patients.…”

“…The authors reported on 172 individuals, including the CREDIBLE-CR patients. Many patients reported adverse events, such as diarrhea or fever, although only four discontinued treatment because of these events [ 59 ]. Finally, there is scarce and inconclusive data on the therapeutic potential of combining CEFID with other antibiotics [ 60 ].…”

What to Do with the New Antibiotics?

“…The high prevalence of heteroresistance to CFD has been proposed as an explanation for the suboptimal efficacy of CFD against carbapenem-resistant bacteria, particularly A. baumannii [ 86 , 87 ]. However, an increasing number of cases of the in vivo emergence of resistance during treatment have been reported [ 70 , 88 , 89 , 90 ].…”