Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli

Compassionate Use of Cefiderocol in the Treatment of an Intraabdominal Infection Due to Multidrug‐Resistant Pseudomonas aeruginosa: A Case Report

“…Cefiderocol is a novel cephalosporin developed by Shionogi & Co., Ltd . Though the agent has poor activity against gram‐positive and anaerobic organisms, cefiderocol has potent activity against gram‐negative bacteria, including lactose‐fermenting and non–lactose‐fermenting organisms .…”

“…The expanded gram‐negative activity, over that of ceftazidime and cefepime, appears to be due to the addition of a catechol moiety to the side chain at position 3 on the β‐lactam ring. This gives cefiderocol its siderophore properties as it complexes with extracellular iron and facilitates penetration into the periplasmic space by bacterial iron transporters, even in the presence of decreased porin channels or increased efflux pumps . It is also stable against a wide array of β‐lactamases including enzymes from each of the four Ambler classifications .…”

“…This is most notably important in the treatment of organisms possessing Ambler class B metallo‐β‐lactamase enzymes, as previously, outside of the monobactam aztreonam, there has been a lack of β‐lactam antibiotic options to treat these organisms. Given that β‐lactam resistance in Pseudomonas aeruginosa is typically driven by the presence of efflux pumps, porin channel alterations, or β‐lactamases, cefiderocol’s stability against these three primary resistance mechanisms lends to its promise in the treatment of multidrug‐resistant (MDR) infections due to this organism, as well as those caused by Acinetobacter baumannii, Stenotrophomonas maltophilia, and carbapenem‐resistant Enterobacteriaceae species . Available evidence demonstrates that cefiderocol has a favorable profile with regard to pharmacokinetics, safety, and tolerability .…”

“…Cefiderocol is a novel cephalosporin developed by Shionogi & Co., Ltd. 1 Though the agent has poor activity against gram-positive and anaerobic organisms, cefiderocol has potent activity against gram-negative bacteria, including lactose-fermenting and non-lactose-fermenting organisms. 2 The expanded gram-negative activity, over that of ceftazidime and cefepime, appears to be due to the addition of a catechol moiety to the side chain at position 3 on the b-lactam ring.…”

“…This gives cefiderocol its siderophore properties as it complexes with extracellular iron and facilitates penetration into the periplasmic space by bacterial iron transporters, even in the presence of decreased porin channels or increased efflux pumps. [1][2][3] It is also stable against a wide array of b-lactamases including enzymes from each of the four Ambler classifications. 1 This is most notably important in the treatment of organisms possessing Ambler class B metallo-b-lactamase enzymes, as previously, outside of the monobactam aztreonam, there has been a lack of b-lactam antibiotic options to treat these organisms.…”