Cefiderocol in context

Abstract

New antibiotics reaching clinical development are scarce, although bacterial plasmids encoding antibiotic resistance genes seem to be everywhere. 1 Madec JY Haenni M Ponsin C et al. Sequence type 48 Escherichia coli carrying the blaCTX-M-1 IncI1/ST3 plasmid in drinking water in France. Antimicrob Agents Chemother. 2016; 60: 6430-6432 Crossref PubMed Scopus (28) Google Scholar Thus, the first clinical trial of cefiderocol, a siderophore cephalosporin active against multidrug-resistant Gram-negative pathogens, 2 Kohira N West J Ito A et al. In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother. 2016; 60: 729-734 Crossref PubMed Scopus (172) Google Scholar reported by Simon Portsmouth and colleagues in The Lancet Infectious Diseases, 3 Portsmouth S van Veenhuyzen D Echols R et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Diseases. 2018; (published online Oct 25.)http://dx.doi.org/10.1016/S1473-3099(18)30554-1 Summary Full Text Full Text PDF PubMed Scopus (198) Google Scholar represents an eagerly-awaited development in the field. The definitive mechanism of action of cefiderocol is not novel; once inside the bacterial cell, it interrupts the synthesis of peptidoglycan, a key component of the bacterial cell wall. What is novel is its manner of getting inside to do the job—no easy task in the era of increasing efflux pump overproduction and porin mutations. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trialIntravenous infusion of cefiderocol (2 g) three times daily was non-inferior compared with imipenem-cilastatin (1 g each) for the treatment of complicated urinary tract infection in people with multidrug-resistant Gram-negative infections. The results of this study will provide the basis for submission of a New Drug Application to the US Food and Drug Administration. Clinical trials of hospital-acquired pneumonia and carbapenem-resistant infections are ongoing. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infections – Author's replyThe enormous efforts of investigators and trial participants in the premarket development of cefiderocol should be neither disregarded nor underestimated: thanks to their work,1 this drug might soon be accessible to patients who might benefit from it. Nonetheless, a drug tested on only a few hundred people and for a few narrow indications will always require additional, postmarket development. As I have stated,2 because we, the public, have demanded an accelerated path to approval, novel antibiotics are now entering the market on the basis of very thin clinical experience. Full-Text PDF Cefiderocol for treatment of complicated urinary tract infectionsWe were pleased to read the generally positive Comment1 regarding our Article,2 published in The Lancet Infectious Diseases. However, we would like to respond to some of the points raised. Full-Text PDF