Dataset Information

Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms.

ABSTRACT: Cefiderocol, formerly S-649266, is a first in its class, an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many β-lactamases, including extended spectrum β-lactamases such as CTX-M, and carbapenemases such as KPC, NDM, VIM, IMP, OXA-23, OXA-48-like, OXA-51-like and OXA-58. Cefiderocol's spectrum of activity encompasses both lactose-fermenting and non-fermenting Gram-negative pathogens, including carbapenem-resistant Enterobacterales. Cefiderocol recently received US Food and Drug Administration approval for the treatment of complicated urinary tract infections, including pyelonephritis, and is currently being evaluated in phase III trials for nosocomial pneumonia and infections caused by carbapenem-resistant Gram-negative pathogens. The purpose of this article is to review existing data on the mechanism of action, microbiology, pharmacokinetics, pharmacodynamics, efficacy, and safety of cefiderocol to assist clinicians in determining its place in therapy.

SUBMITTER: Wu JY

PROVIDER: S-EPMC7054475 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms.

Wu Janet Y JY Srinivas Pavithra P Pogue Jason M JM

Infectious diseases and therapy 20200218 1

Cefiderocol, formerly S-649266, is a first in its class, an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many β-lactamases, including extended spectrum β-lactamases such as CTX-M, and carbapenemases such as KPC, NDM, VIM, IMP, OXA-23, OXA-48-like, OXA-51-like and OXA-58. Cefiderocol's spect ...[more]

PMID: 32072491

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Project description:BackgroundThis study evaluated the in vitro activity of cefiderocol, ceftazidime/avibactam, and aztreonam/avibactam against clinically important multidrug-resistant non-fermenting Gram-negative bacilli.MethodsBacteraemic isolates of 126 multidrug-resistant Acinetobacter baumannii (MDRAB), 110 imipenem-resistant Pseudamoas aeruginosa [including 14 difficult-to-treat resistant P. aeruginosa (DTRPA)], 45 beta-lactam-non-susceptible Burkholderia cepacia complex (BCC), 47 levofloxacin or trimethoprim/sulfamethoxazole-non-susceptible Stenotrophomonas maltophilia and 22 ciprofloxacin-non-susceptible Elizabethkingia spp. collected between 2019 and 2021 were subjected to MIC determination for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam.ResultsThe MIC50/90s of ceﬁderocol for drug-resistant A. baumannii, P. aeruginosa, BCC, S. maltophilia and Elizabethkingia spp. were 0.25/2, 0.25/1, ≤0.06/≤0.06, ≤0.06/0.25 and >32/>32 mg/L, respectively. Cefiderocol inhibited 94.4% (119/126) of MDRAB, 100% of imipenem-resistant P. aeruginosa, 100% of DTRPA and 100% of BCC at an MIC ≤4 mg/L, and 97.9% (46/47) of S. maltophilia at ≤1 mg/L. Ceftazidime/avibactam inhibited 76.4% (84/110) of imipenem-resistant P. aeruginosa, 21.4% (3/14) of DTRPA and 68.9% (31/45) of BCC at an MIC ≤8 mg/L. Aztreonam/avibactam had MIC50/90s of 16/>32, 8/16 and 4/8 mg/L for imipenem-resistant P. aeruginosa, BCC and S. maltophilia, respectively. At ≤8 mg/L, aztreonam/avibactam inhibited 7.1% (1/14) of DTRPA and 93.6% (44/47) of S. maltophilia isolates. Elizabethkingia spp. demonstrated high MICs for cefiderocol, ceftazidime/avibactam and aztreonam/avibactam, with all MIC50s and MIC90s > 32 mg/L.ConclusionCefiderocol may serve as an alternative treatment for multidrug-resistant A. baumannii, P. aeruginosa, BCC and S. maltophilia when other antibiotics have been ineffective or intolerable. The role of ceftazidime/avibactam and aztreonam/avibactam in the management of BCC or S. maltophilia infections warrants further investigation.

Dataset Information

Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms.

Publications

Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms.

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