Cefiderocol: A Novel Siderophore Cephalosporin Defeating Carbapenem-resistant Pathogens

Bonomo, Robert A

doi:10.1093/cid/ciz823

Cited by 40 publications

(29 citation statements)

References 23 publications

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“…Teixobactin, discovered in 2015 and currently in clinical trials, was the first new antibiotic developed in 27 years [ 20 , 21 ]. The promising new β-lactam cefiderocol is a siderophore-modified cephalosporin active against carbapenem-resistant Gram-negative bacteria and was approved by the Food and Drug Administration of the United States (FDA), Department of Health and Human Services in 2019 [ 22 , 23 , 24 , 25 ]. Alternative treatments resort to the design and development of compounds that are able to inhibit resistance mechanisms and can be co-administered with already known antibiotics, aiming to prolong their clinically useful lifetime [ 8 ].…”

Section: Antibiotic Resistance Mediated By β-Lactamasesmentioning

confidence: 99%

Metallo-β-Lactamase Inhibitors Inspired on Snapshots from the Catalytic Mechanism

et al. 2020

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β-Lactam antibiotics are the most widely prescribed antibacterial drugs due to their low toxicity and broad spectrum. Their action is counteracted by different resistance mechanisms developed by bacteria. Among them, the most common strategy is the expression of β-lactamases, enzymes that hydrolyze the amide bond present in all β-lactam compounds. There are several inhibitors against serine-β-lactamases (SBLs). Metallo-β-lactamases (MBLs) are Zn(II)-dependent enzymes able to hydrolyze most β-lactam antibiotics, and no clinically useful inhibitors against them have yet been approved. Despite their large structural diversity, MBLs have a common catalytic mechanism with similar reaction species. Here, we describe a number of MBL inhibitors that mimic different species formed during the hydrolysis process: substrate, transition state, intermediate, or product. Recent advances in the development of boron-based and thiol-based inhibitors are discussed in the light of the mechanism of MBLs. We also discuss the use of chelators as a possible strategy, since Zn(II) ions are essential for substrate binding and catalysis.

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Section: Antibiotic Resistance Mediated By β-Lactamasesmentioning

confidence: 99%

Metallo-β-Lactamase Inhibitors Inspired on Snapshots from the Catalytic Mechanism

et al. 2020

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“…Several studies showed in vitro activity of cefiderocol against CR-GNB [5,6]. Regarding CR Enterobacterales, in vitro activity of cefiderocol was more potent than meropenem, ceftazidime-avibactam or ceftolozane-tazobactam, as with our XDR E. hormaechei strain [6].…”

Section: Discussionmentioning

confidence: 59%

Compassionate Use of Cefiderocol to Treat a Case of Prosthetic Joint Infection Due to Extensively Drug-Resistant Enterobacter hormaechei

et al. 2020

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We report the case of a 67-year old man with a right knee prosthetic joint infection due to extensively drug-resistant Enterobacter hormaechei. The resistance phenotype was due to the overproduction of the intrinsic cephalosporinase (ACT-5) associated with the production of three acquired β-lactamases (CTX-M-15, TEM-1B and OXA-1), and a putative membrane decreased permeability. He was first treated with colistin-tigecyclin due to adverse drug reactions; treatment was switched to cefiderocol for a 12-week antibiotic duration, with a favorable outcome.

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“…This novel cephalosporin, developed in Japan, ( 156 ) was FDA approved in 2019 ( 157 ). Cefiderocol is a β-lactam antimicrobial, exerting its principal mechanism of action through inhibition of the cell wall synthesis of Gram-negative pathogens ( 158 ). It possesses a similar mode of action topenicillin—the first antibiotic.…”

Section: History Of Antibiotics In the Last Millenniummentioning

confidence: 99%

Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter

Dhingra

Rahman

Peile

et al. 2020

Front. Public Health

216

137

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Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.

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Cefiderocol: A Novel Siderophore Cephalosporin Defeating Carbapenem-resistant Pathogens

Cited by 40 publications

References 23 publications

Metallo-β-Lactamase Inhibitors Inspired on Snapshots from the Catalytic Mechanism

Metallo-β-Lactamase Inhibitors Inspired on Snapshots from the Catalytic Mechanism

Compassionate Use of Cefiderocol to Treat a Case of Prosthetic Joint Infection Due to Extensively Drug-Resistant Enterobacter hormaechei

Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter

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