Humanized Exposures of Cefiderocol, a Siderophore Cephalosporin, Display Sustained in vivo Activity against Siderophore-Resistant Pseudomonas aeruginosa

Islam M. Ghazi, Marguerite L. Monogue, Masakatsu Tsuji, David P. Nicolau

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)278-284
Number of pages7
JournalPharmacology
Volume101
Issue number5-6
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Keywords

  • Cefiderocol
  • Humanized exposure
  • In vivo activity
  • Pseudomonas aeruginosa
  • Siderophore

ASJC Scopus subject areas

  • Pharmacology

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