Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Abstract

Intravenous cefiderocol (Fetroja ® ; Fetcroja ® ) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01580-4.

Emergence of High-Level Cefiderocol Resistance in Carbapenem-Resistant Klebsiella pneumoniae from Bloodstream Infections in Patients with Hematologic Malignancies in China

“…Cefiderocol is a promising novel cephalosporin antibiotic showing expanded activity against Gram-negative bacteria producing all four Ambler classes of β-lactamases, including extended spectrum β-lactamases (ESBL) and carbapenemases. In meropenem-nonsusceptible strains in SIDERO-WT study, more than 99% Enterobacterales and Pseudomonas aeruginosa were susceptible to cefiderocol ( 17 ). In SIDERO-CR study, the susceptibility rate for meropenem-nonsusceptible is 97% ( 18 ).…”

How the Presence of Hemin Affects the Expression of the Different Iron Uptake Pathways in Pseudomonas aeruginosa Cells

“…Cefiderocol, one such siderophore-antibiotic conjugate developed by Shionogi, has been approved by the European Medicine Agency in April 2020 for the treatment of infections due to aerobic Gram-negative organisms. 46,47 One major bottleneck limiting the development of siderophore-antibiotic conjugates is that bacteria are equipped with several iron uptake strategies, heme and ferri-siderophores uptake pathways. To make vectorization of antibiotics by siderophores successful, it is important to understand how bacteria select and synchronize the expression of their different iron import pathways in response to different iron sources.…”

Empiric treatment of patients with sepsis and septic shock and place in therapy of cefiderocol: a systematic review and expert opinion statement

“…New antimicrobial combinations have been tested, both including non-β-lactamase inhibitors and β-lactamase inhibitors (e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam) with partial success, because of the instability of beta lactamase ring or the non-susceptibility of some A. baumannii strains. Effective and timely treatments for MBL-producing Gram-negative-related infections are still an unmet medical need [ 7 ]; thus, new guidelines and new therapies have to be developed. In this scenario, cefiderocol turned out to be a valid option.…”