Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

Kaye, Keith S.; Naas, Thierry; Pogue, Jason M.; Rossolini, Gian María

doi:10.1007/s40121-023-00773-6

Cited by 33 publications

(12 citation statements)

References 146 publications

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“…Cefodilol exhibits inherent stability against a wide range of carbapenemases, including class A, B, and D, as well as class C cephalosporinase hydrolases. Patients infected with KPC, NDM, VIM, IMP, and OXA-48 harboring CRE experiencing BSI or urinary tract infections can potentially benefit from cefodilol therapy ( 56 ). However, it is important to acknowledge that resistance may arise when cefiderocol is employed in the treatment of CRE.…”

Section: Treatment Optionsmentioning

confidence: 99%

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention – a comprehensive review

Li,

Zhou,

Yang

et al. 2024

Front. Public Health

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Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.

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Section: Treatment Optionsmentioning

confidence: 99%

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention – a comprehensive review

Li,

Zhou,

Yang

et al. 2024

Front. Public Health

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“…Finally, some are exploring “trojan horse” approaches, in which receptors and transporters for required nutrients, such as iron, are subverted to facilitate antibiotic entry . A recently approved example is cefiderocol, which combines siderophore activity with a cephalosporin antibiotic, thus subverting the iron transport machinery of Gram-negative bacteria to gain access across the outer membrane . Future efforts could combine these strategies, leveraging both computational approaches and ongoing characterization of bacterial receptors, transporters, and porins to overcome the formidable cell envelope barrier.…”

Section: Barriers To Small-molecule Antibiotic Drug Development and P...mentioning

confidence: 99%

Small-Molecule Antibiotic Drug Development: Need and Challenges

Bergkessel,

Forte,

Gilbert

2023

ACS Infect. Dis.

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The need for new antibiotics is urgent. Antimicrobial resistance is rising, although currently, many more people die from drug-sensitive bacterial infections. The continued evolution of drug resistance is inevitable, fueled by pathogen population size and exposure to antibiotics. Additionally, opportunistic pathogens will always pose a threat to vulnerable patients whose immune systems cannot efficiently fight them even if they are sensitive to available antibiotics, according to clinical microbiology tests. These problems are intertwined and will worsen as human populations age, increase in density, and experience disruptions such as war, extreme weather events, or declines in standard of living. The development of appropriate drugs to treat all the world's bacterial infections should be a priority, and future success will likely require combinations of multiple approaches. However, the highest burden of bacterial infection is in Low-and Middle-Income Countries, where limited medical infrastructure is a major challenge. For effectively managing infections in these contexts, small-molecule-based treatments offer significant advantages. Unfortunately, support for ongoing small-molecule antibiotic discovery has recently suffered from significant challenges related both to the scientific difficulties in treating bacterial infections and to market barriers. Nevertheless, small-molecule antibiotics remain essential and irreplaceable tools for fighting infections, and efforts to develop novel and improved versions deserve ongoing investment. Here, we first describe the global historical context of antibiotic treatment and then highlight some of the challenges surrounding small-molecule development and potential solutions. Many of these challenges are likely to be common to all modalities of antibacterial treatment and should be addressed directly.

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“…In the face of rising carbapenem resistance [ 7 ], cefiderocol (CEF), a siderophore-conjugated cephalosporin, has recently emerged as a novel antibiotic with an unprecedented mode of action [ 119 ]. CEF was granted FDA approval in November 2019 and is used to treat cUTIs [ 120 ].…”

Section: New Routes With Cefiderocol: From In Silico Studies To Marketmentioning

confidence: 99%

All Roads Lead to Rome: Enhancing the Probability of Target Attainment with Different Pharmacokinetic/Pharmacodynamic Modelling Approaches

Khalid

2023

Antibiotics

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In light of rising antimicrobial resistance and a decreasing number of antibiotics with novel modes of action, it is of utmost importance to accelerate development of novel treatment options. One aspect of acceleration is to understand pharmacokinetics (PK) and pharmacodynamics (PD) of drugs and to assess the probability of target attainment (PTA). Several in vitro and in vivo methods are deployed to determine these parameters, such as time-kill-curves, hollow-fiber infection models or animal models. However, to date the use of in silico methods to predict PK/PD and PTA is increasing. Since there is not just one way to perform the in silico analysis, we embarked on reviewing for which indications and how PK and PK/PD models as well as PTA analysis has been used to contribute to the understanding of the PK and PD of a drug. Therefore, we examined four recent examples in more detail, namely ceftazidime-avibactam, omadacycline, gepotidacin and zoliflodacin as well as cefiderocol. Whereas the first two compound classes mainly relied on the ‘classical’ development path and PK/PD was only deployed after approval, cefiderocol highly profited from in silico techniques that led to its approval. Finally, this review shall highlight current developments and possibilities to accelerate drug development, especially for anti-infectives.

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Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

Cited by 33 publications

References 146 publications

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention – a comprehensive review

Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention – a comprehensive review

Small-Molecule Antibiotic Drug Development: Need and Challenges

All Roads Lead to Rome: Enhancing the Probability of Target Attainment with Different Pharmacokinetic/Pharmacodynamic Modelling Approaches

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