Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial

Portsmouth, Simon; Veenhuyzen, David van; Echols, Roger; Machida, Mitsuaki; Ferreira, Juan Camilo Arjona; Ariyasu, Mari; Tenke, Péter; Nagata, Tsutae Den

doi:10.1016/s1473-3099(18)30554-1

Cited by 316 publications

(295 citation statements)

References 21 publications

Supporting

Mentioning

281

Contrasting

Unclassified

Order By: Relevance

“…Step-down or switch to oral antibiotics was not permitted in this study. Key exclusion criteria included baseline urine culture with more than 2 pathogens, fungal urinary tract infection, carbapenem-resistant pathogens, and CrCl \ 20 mL/min [39].…”

Section: Clinical Efficacymentioning

confidence: 99%

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

2020

View full text Add to dashboard Cite

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 b-lactamases, including extended spectrum b-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 lactosefermenting 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.

show abstract

Section: Clinical Efficacymentioning

confidence: 99%

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

2020

View full text Add to dashboard Cite

show abstract

“…Galán-Puchades hypothesises that Wolbachia spp released during the natural death of O volvulus (adults or microfilariae) induce inflammatory processes that trigger epilepsy, which would indeed justify distinguishing wolbachia from the worm in our study. Should this hypothesis be true, the release of Wolbachia spp into the blood after treatment with diethylcarbamazine or ivermectin (a demonstrated occurrence) 3 would, as Galán-Puchades suggests, induce an epidemic of seizures after mass treatment with these drugs. However, such an event has never been reported with either drug, even in populations with extremely high microfilarial densities (eg, the Vina valley in northern Cameroon).…”

Section: Authors' Replymentioning

confidence: 99%

“…Another new drug is cefiderocol, the first siderophore-antibiotic conjugate to reach late stage clinical testing, which was developed for treatment of complicated urinary tract infections. 3 Siderophore antibiotics bind to free iron and use the bacterial active iron transport channels to cross the outer membrane of Gram-negative bacteria and reach the periplasmic space. In sufficient for treatment of complicated urinary tract infections with or without pyelonephritis.…”

Section: Cefiderocol For Treatment Of Complicated Urinary Tract Infecmentioning

confidence: 99%

Cefiderocol for treatment of complicated urinary tract infections

Wagenlehner

Naber

2019

The Lancet Infectious Diseases

View full text Add to dashboard Cite

“…Cefiderocol recently received FDA approval for the treatment of complicated urinary tract infections 9 , on the basis of non-inferiority against imipenem/cilastatin 10 . A trial versus meropenem for nosocomial pneumonia has also been completed 5,11 with efficacy demonstrated against Gram-negative pathogens such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Burkholderia pseudomalleiclinical isolates are highly susceptiblein vitroto cefiderocol, a novel siderophore cephalosporin

Burnard

Robertson

Henderson

et al. 2020

Preprint

View full text Add to dashboard Cite

Cefiderocol is a novel cephalosporin designed to treat multidrug resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greater in vitro activity against many Gram-negative bacilli than currently used carbapenems, β-lactam/β-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated the in vitro activity of cefiderocol (S-649266) against a total of 271 clinical isolates of Burkholderia pseudomallei from Australia. The collection was comprised of primary isolates (92.3%) and subsequent isolates (7.7%). Minimum inhibitory concentrations (MIC) of cefiderocol ranged from ≤0.03 to 32 mg/L, where the MIC90 was 1 mg/L and 16 mg/L for primary and subsequent isolates, respectively. Based upon non-species specific (Gram-negative bacilli) clinical breakpoints for cefiderocol (MIC ≤ 4 mg/L), twelve isolates (4.4%) would be classified as non-susceptible. Further testing for co-resistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline was performed on a subset of isolates with elevated cefiderocol MICs (≥2 mg/L, 4.8%) and 84.6% of these isolates exhibited resistance to at least one of these antimicrobials. Cefiderocol was found to be highly active in vitro against B. pseudomallei primary clinical isolates. This novel compound shows great potential for the treatment of melioidosis in endemic countries and should be explored further.

show abstract

Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial

Cited by 316 publications

References 21 publications

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

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

Cefiderocol for treatment of complicated urinary tract infections

Burkholderia pseudomalleiclinical isolates are highly susceptiblein vitroto cefiderocol, a novel siderophore cephalosporin

Contact Info

Product

Resources

About