Pharmacodynamics of cefiderocol, a novel siderophore cephalosporin, in a Pseudomonas aeruginosa neutropenic murine thigh model

Ghazi, Islam M.; Monogue, Marguerite L.; Tsuji, Masakatsu

doi:10.1016/j.ijantimicag.2017.10.008

Cited by 42 publications

(56 citation statements)

References 28 publications

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“…In a recent work, scientists gave an injection of cefiderocol to infected mice in different single doses and drew blood samples within the time course of the experiment. The free-drug concentration was detected with an LC-MS/MS method, and a concentration-time profile was described for PK analysis (Ghazi et al, 2018). Additionally, clinical research was performed to evaluate the PK of cefiderocol after intravenous infusion to healthy adults, and the concentration in human plasma and urine was evaluated with an LC-MS/MS method as well (Saisho et al, 2018).…”

Section: Discovery and Development Of Siderophore-based Novel Drugsmentioning

confidence: 99%

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Luo

Guo

et al. 2018

Mass Spectrometry Reviews

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Siderophores are chemically diverse small molecules produced by microorganisms for chelation of irons to maintain their survival and govern some important biological functions, especially those cause that infections in hosts. Still, siderophores can offer new insight into a better understanding of the diagnosis and treatments of infectious diseases from the siderophore biosynthesis and regulation perspective. Thus, this review aims to summarize the biomedical value and applicability of siderophores in pathogenic contexts by briefly reviewing mass spectrometry (MS)-based chemical biology and translational applications that involve diagnosis, pathogenesis, and therapeutic discovery for a variety of infectious conditions caused by different pathogens. We highlight the advantages and disadvantages of siderophore discovery and applications in pathogenic contexts. Finally, we propose a panel of new and promising strategy as precision-modification metabolomics method, to rapidly advance the discovery of and translational innovations pertaining to these value compounds in broad biomedical niches. © 2018 Wiley Periodicals, Inc. Mass Spec Rev XX:XX-XX, 2018.

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Section: Discovery and Development Of Siderophore-based Novel Drugsmentioning

confidence: 99%

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Luo

Guo

et al. 2018

Mass Spectrometry Reviews

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“…In fact, the conjugation of ATBs with siderophores, peptides (eg, AMPs and cell‐penetrating peptides [CPPs]), antibodies, and nanoparticles (NPs) are effective representative examples of the Trojan horse strategy. These approaches have resulted in many candidates demonstrating potent antibacterial activity and some of these candidates are currently at the clinical investigation stage . To that end, a review summarizing the recent advances in findings and the different perspectives on prevalent Trojan horse strategies in ATB research, would be useful to all scientists in the field.…”

Section: Introductionmentioning

confidence: 99%

“…These approaches have resulted in many candidates demonstrating potent antibacterial activity and some of these candidates are currently at the clinical investigation stage. 36 To that end, a review summarizing the recent advances in findings and the different perspectives on prevalent Trojan horse strategies in ATB research, would be useful to all scientists in the field. In this paper, we aim to present up-to-date knowledge of recent advances in ATB drug delivery systems using the Trojan horse strategy to overcome the resistance of pathogenic microbes.…”

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confidence: 99%

“…165 (59) was covalently attached to (60) through a glutaric anhydride linker to create the conjugate CAP-UBI 29-41 (61, Figure 12). The ester bond between CAP and glutaric-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] part can be easily broken by enzymatic hydrolysis. 165,166 CAP and its conjugate (61) were then evaluated for their antibacterial activity as well as their cytotoxicity on normal cells (Table 8).…”

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confidence: 99%

“…165 Both CAP and conjugate (61) exhibited greater effects in Gram-negative (ie, E. coli) than in Gram-positive bacteria (ie, S. aureus). The attachment of UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] (60) to CAP (59) is likely favorable to antibiotic permeability and ATB activity. In terms of biocytotoxicity, CAP caused a remarkable decrease in the population of leukocytes and neutrophils when compared to the control (ie, saline) (4.46 and 0.24 × 10 9 /L vs 8.17 and 1.46 × 10 9 /L, respectively).…”

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confidence: 99%

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Drug delivery systems designed to overcome antimicrobial resistance

Pham

Loupias

Dassonville‐Klimpt

et al. 2019

Medicinal Research Reviews

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Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.

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Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]‐Cefiderocol (S‐649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration

Miyazaki

Katsube

Shen³

et al. 2019

The Journal of Clinical Pharma

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The objectives of this study were to characterize the concentration‐time profiles of total radioactivity equivalent and unchanged cefiderocol, the route(s) of elimination and mass balance, and safety of cefiderocol after intravenous administration of a single 1000‐mg (100 μCi) dose of [ 14 C]‐cefiderocol as a 1‐hour infusion in healthy adult male subjects. Unchanged cefiderocol accounted for the majority of total radioactivity in plasma, and the partitioning of total radioactivity into red blood cells was negligible. The recovery of total radioactivity was complete in all subjects within 120 hours after initiation of the infusion (101.5% of the administered dose). Cefiderocol‐related material was primarily excreted into urine, with 98.7% of the administered dose of [ 14 C]‐cefiderocol excreted as total radioactivity into urine and negligible excretion into feces. Based on the results of metabolite profiling, cefiderocol accounted for 92.3% of area under the concentration‐time curve of total radioactivity in plasma and accounted for 90.6% of the administered dose excreted into urine. Metabolism was a minor route of elimination for cefiderocol. Cefiderocol was generally safe and well tolerated in healthy adult male subjects. In conclusion, unchanged cefiderocol represents the majority of total radioactivity in plasma. Cefiderocol is primarily excreted as unchanged drug into urine. This study indicates that cefiderocol and drug‐related material did not remain in the body.

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Pharmacodynamics of cefiderocol, a novel siderophore cephalosporin, in a Pseudomonas aeruginosa neutropenic murine thigh model

Cited by 42 publications

References 28 publications

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Drug delivery systems designed to overcome antimicrobial resistance

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]‐Cefiderocol (S‐649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration

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Pharmacodynamics of cefiderocol, a novel siderophore cephalosporin, in a Pseudomonas aeruginosa neutropenic murine thigh model

Cited by 42 publications

References 28 publications

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts

Drug delivery systems designed to overcome antimicrobial resistance

Metabolism, Excretion, and Pharmacokinetics of [14C]‐Cefiderocol (S‐649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration

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Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]‐Cefiderocol (S‐649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration