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Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Lívia Maria Batista Vilela, Carlos André dos Santos-Silva, Ricardo Salas Roldan-Filho, Pollyanna Michelle da Silva, Marx de Oliveira Lima, José Rafael da Silva Araújo, Wilson Dias de Oliveira, Suyane de Deus e Melo, Madson Allan de Luna Aragão, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Ana Christina Brasileiro-Vidal, Ana Maria Benko-Iseppon
According to the repository of antimicrobial peptides (DRAMP) (Kang et al. 2019), until July 2020, there were 76 AMPs under development to be used as drugs in the different preclinical and clinical phases. Although interest in these molecules is growing, only a small part is available to the population as a drug; until 2018, only 1% of the studied peptides reached the earlier registration stage (Lau and Dunn 2018). Further growth is expected, as approximately 140 peptide drugs have been used in clinical trials and more than 600 peptides are in the pre-clinical and clinical testing phase. Most likely, other compounds will be approved by the FDA between 2019 and 2021, including cefiderocol, imipenem-relebactam, and lefamulin (Fosgerau and Hoffmann 2015; Schulz et al. 2019).
Cefiderocol (S-649266)
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Cefiderocol (S-649266) is a novel siderophore cephalosporin, initially developed jointly by Shionogi Inc. and Glaxo Smith Kline. From November 9, 2015, further development was by Shionogi alone. By virtue of In vitro activity against carbapenem-resistant Enterobacteriaceae (CRE), including those producing Klebsiella pneumoniae carbapenemase (KPC) type enzymes or metallo-beta-lactamases (e.g. New Delhi metallo-beta-lactamase [NDM]), plus activity against carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, the antibiotic has enormous promise. Initiation of phase III trials for treatment of CRE commenced in March 2016.
All-cause mortality rates in adults with carbapenem-resistant Gram-negative bacterial infections: a comprehensive review of pathogen-focused, prospective, randomized, interventional clinical studies
Published in Expert Review of Anti-infective Therapy, 2022
Thomas P. Lodise, Matteo Bassetti, Ricard Ferrer, Thierry Naas, Yoshihito Niki, David L. Paterson, Markus Zeitlinger, Roger Echols
There is still a clear need for well-designed, larger pathogen-focused clinical studies [48]. PF-RCTs are challenging but necessary to gain a better understanding on the efficacy or effectiveness of antibiotics against the WHO priority pathogens. Although several antibiotics have recently been approved with activity against CR bacteria, they have varying in vitro activity against CR pathogens and stability against common carbapenemases. Of the new treatment options reviewed, cefiderocol has the broadest spectrum of activity against CR lactose- and non-lactose fermenters, such as A. baumannii or P. aeruginosa. To move away from the polymyxin-based therapies with increased toxicity, new treatment options are still needed, supported by prospective RCTs enrolling the type of patients in whom these agents are likely to be utilized.
Pharmacotherapeutic management of bronchial infections in adults: non-cystic fibrosis bronchiectasis and chronic obstructive pulmonary disease
Published in Expert Opinion on Pharmacotherapy, 2020
Marta Di Pasquale, Stefano Aliberti, Marco Mantero, Andrea Gramegna, Francesco Blasi
Cefiderocol is an iv cephalosporin effective against multidrug-resistant gram-negative bacteria, including carbapenemase-producing organisms and P. aeruginosa resistant to other beta-lactams. As other beta-lactams, it inhibits the bacterial cell wall synthesis, however due to its siderophore-like property, it enters the bacterial periplasm and has enhanced stability to β-lactamases [92]. It seems that the microbiological activity of cefiderocol against aerobic Gram-negative bacilli (especially P. aeruginosa, S. maltophilia and B. cepacia) and A. baumannii is equal to or superior to that of ceftazidime-avibactam and meropenem. Cefiderocol’s efficacy against K. pneumoniae carbapenemase (KPC)-producing seems to be comparable or superior to ceftazidime-avibactam and colistin based regimens. The current dosing regimen being used in phase III studies is 2 g administered intravenously every 8 h (q8 h) using a 3-h infusion. Dosage adjustment is required for both augmented renal clearance and in patients with moderate to severe renal impairment. Two phase III clinical trials are currently being conducted to evaluate the treatment of serious respiratory infections in adult patients caused by carbapenem-resistant Gram-negative pathogens. Cefiderocol appears to be well tolerated with a side effect profile that is comparable to other cephalosporin antimicrobials.
The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria
Published in Expert Opinion on Pharmacotherapy, 2018
Michael E. Plazak, Pranita D. Tamma, Emily L. Heil
The development of cefiderocol, a unique siderophore cephalosporin, is arguably the most intriguing addition to the antibiotic armamentarium. Similar to the other cephalosporins currently deployed in clinical practice, the cephalosporin component of cefiderocol complexes with PBP3 preventing the transpeptidation step of bacterial cell wall synthesis. However, the catechol moiety on the side chain of the cephalosporin is what makes this antimicrobial agent truly unique. This addition allows for cefiderocol to complex with ferric iron, deceiving the bacteria into cellular uptake of the antibiotic through the bacterial iron transport system. The uptake through iron transporters accelerates the concentration of active drug inside the cell, ultimately resulting in broad-spectrum activity against Enterobacteriaceae producing KPC, VIM, IMP, NDM, and OXA-48-like carbapenemases. Cefiderocol also seems to be highly active against lactose non-fermenters including carbapenem-resistant P. aeruginosa, A. baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia complex [92].