cefiderocol and Disease-Models--Animal

We evaluated the in vivo efficacy of humanized exposures of cefiderocol, a novel siderophore cephalosporin, against a test panel of P. aeruginosa (PSA) previously shown to develop resistance to 2 preclinical candidate siderophores (MB-1 and SMC-3176). In the thigh infection model, the PSA bacterial density in untreated controls grew from 5.54 ± 0.23 to 8.68 ± 0.57 log10 CFU over 24 h. The humanized cefiderocol exposure resulted in >1 log10 CFU reduction in all 8 isolates, while MB-1 and SMC-3176 exhibited variable activity similar to that previously reported. Humanized exposures of cefepime and levofloxacin, acting as positive antimicrobial controls displayed activity consistent with that of the bacterial phenotypic susceptibility profiles. Cefiderocol manifested in vivo efficacy against all PSA isolates including those resistant to cefepime and levofloxacin in contrast to its predecessor siderophore compounds. These preclinical data are supportive of further evaluation of cefiderocol in the treatment of P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Azetidines; Cefepime; Cefiderocol; Cephalosporins; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Humans; Levofloxacin; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Monobactams; Pseudomonas aeruginosa; Pyridones; Siderophores; Sulfonamides

Cefiderocol (S-649266), a novel siderophore cephalosporin, shows potent activity against carbapenem-resistant Gram-negative bacilli. In this study, we evaluated the efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli (

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; Cefiderocol; Cephalosporins; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections