Activities of Cefiderocol with Simulated Human Plasma Concentrations against Carbapenem-Resistant Gram-Negative Bacilli in an
            <i>In Vitro</i>
            Chemostat Model

Matsumoto, Shuhei; Kanazawa, Sachi; Sato, Takafumi; Yamano, Yoshinori

doi:10.1128/aac.01128-20

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…With the humanized regimen, increasing the infusion period from 1 to 3 h increased % f T > MIC for MICs of 4 mg/L (from 75% to 100%) and 8 mg/L (from 50% to 100%) in immunocompetent rat models [ 57 ]. Results from an in vitro chemostat model were consistent with those from animal studies [ 34 ].…”

Section: Pharmacodynamic Propertiessupporting

confidence: 81%

“…In SIDERO-CR, 1873 carbapenem–nonsusceptible isolates, including Enterobacterales, MDR A. baumannii , MDR P. aeruginosa , and S. maltophilia were collected globally between 2014 and 2016. In vitro data are also available from other studies assessing cefiderocol against a wide range of clinically important isolates collected globally [ 14 , 28 – 30 ] and from Canada [ 31 ], Germany [ 32 ], Greece [ 33 ], Japan [ 34 , 35 ], Spain [ 36 ], Taiwan [ 37 ], the UK [ 38 ] and the USA [ 17 , 39 – 42 ].…”

Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

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Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Syed

2021

Drugs

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Intravenous cefiderocol (Fetroja ® ; Fetcroja ® ) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01580-4.

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Section: Pharmacodynamic Propertiessupporting

confidence: 81%

Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Syed

2021

Drugs

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“…Twenty-five studies investigated the characteristics of PK and/or PD of cefiderocol ( Katsube et al, 2016 ; Katsube et al, 2017 ; Matsumoto et al, 2017 ; Monogue et al, 2017 ; Ghazi et al, 2018a ; Ghazi et al, 2018b ; Katsube et al, 2018 ; Kawaguchi et al, 2018 ; Saisho et al, 2018 ; Katsube et al, 2019a ; Kidd et al, 2019a ; Katsube et al, 2019b ; Kidd et al, 2019b ; Chen et al, 2019 ; Miyazaki et al, 2019 ; Nakamura et al, 2019 ; Stainton et al, 2019 ; Matsumoto et al, 2020 ; Ota et al, 2020 ; Gill et al, 2021 ; Katsube et al, 2021 ; Kawaguchi et al, 2021 ; Kobic et al, 2021 ; König et al, 2021 ; Nakamura et al, 2021 ). A phase I study including healthy Japanese and Caucasian volunteers showed exhibit linear PK at doses of up to 2,000 mg, with low to moderate interindividual variability ( Saisho et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Considering that the bactericidal activity of β-lactam antibiotics can be enhanced by prolonging the infusion time, the recommended standard dose regimen for cefiderocol is 2g q8h with a 3-h infusion ( Fetroja (Cefiderocol), 2021 ). An in vitro PK/PD study showed that the standard dose could completely kill meropenem-resistant gram-negative isolates showing cefiderocol MICs of 0.5–4 g/ml within 24 h ( Matsumoto et al, 2020 ). Nine animal studies using neutropenic murine thigh models or respiratory tract infection models mimicking humanized exposures (2g q8h with a 3-h infusion) showed a >1 log 10 reduction in bacterial colony forming units (CFU) of most Gram-negative bacteria with MICs ≤4 g/ml, but not for the isolates with MICs ≥ 8 mg/L ( Supplementary Table S1 ) ( Matsumoto et al, 2017 ; Monogue et al, 2017 ; Ghazi et al, 2018b ; Kidd et al, 2019b ; Chen et al, 2019 ; Stainton et al, 2019 ; Ota et al, 2020 ; Gill et al, 2021 ; Nakamura et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

et al. 2022

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Cefiderocol is a novel synthetic siderophore-conjugated antibiotic that hijacks the bacterial iron transport systems facilitating drug entry into cells, achieving high periplasmic concentrations. This systematic review analyzed the currently available literature on cefiderocol. It summarized in vitro susceptibility data, in vivo antimicrobial activity, pharmacokinetics/pharmacodynamics (PK/PD), clinical efficacy, safety and resistance mechanisms of cefiderocol. Cefiderocol has potent in vitro and in vivo activity against multidrug-resistant (MDR) Gram-negative bacteria, including carbapenem-resistant isolates. But New Delhi Metallo-β-lactamase (NDM)- positive isolates showed significantly higher MICs than other carbapenemase-producing Enterobacterales, with a susceptible rate of 83.4% for cefiderocol. Cefiderocol is well-tolerated, and the PK/PD target values can be achieved using a standard dose regimen or adjusted doses according to renal function. Clinical trials demonstrated that cefiderocol was non-inferiority to the comparator drugs in treating complicated urinary tract infection and nosocomial pneumonia. Case reports and series showed that cefiderocol was a promising therapeutic agent in carbapenem-resistant infections. However, resistant isolates and reduced susceptibility during treatment to cefiderocol have already been reported. In conclusion, cefiderocol is a promising powerful weapon for treating MDR recalcitrant infections.

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“…The preclinical dose-finding experiments in murine models supported the administration of cefiderocol 2 g every 8 h in 3-h infusions, which achieved bactericidal effects against Gram-negative bacteria with cefiderocol MIC values up to 4 lg/mL [127]. The in vivo efficacy of cefiderocol against E. coli and K. pneumoniae has been demonstrated in neutropenic murine thigh infection and lung infection models, as well as in an immunocompetent rat lung infection model and in an in vitro chemostat model [128][129][130][131][132].…”

Section: Pharmacokinetics/pharmacodynamics and Effectiveness Of Cefid...mentioning

confidence: 91%

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

et al. 2023

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Carbapenem-resistant Enterobacterales (CRE) remain a significant public health threat, and, despite recent approvals, new antibiotics are needed. Severe infections caused by CRE, such as nosocomial pneumonia and bloodstream infections, are associated with a relatively high risk of morbidity and mortality. The recent approval of ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, plazomicin, eravacycline and cefiderocol has broadened the armamentarium for the treatment of patients with CRE infections.Cefiderocol is a siderophore cephalosporin with overall potent in vitro activity against CRE. It is taken up via iron transport channels through active transport, with some entry into bacteria through traditional porin channels. Cefiderocol is relatively stable against hydrolysis by most serine-and metallo-beta-lactamases, including KPC, NDM, VIM, IMP and OXA carbapenemases-the most frequent carbapenemases detected in CRE. The efficacy and safety of cefiderocol has been demonstrated in three randomised, prospective, parallel group or controlled clinical studies in patients at risk of being infected by multidrug-resistant or carbapenem-resistant Gram-negative bacteria. This paper reviews the in vitro activity, emergence of resistance, preclinical effectiveness, and clinical experience for cefiderocol, and its role in the management of patients with CRE infections.

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Activities of Cefiderocol with Simulated Human Plasma Concentrations against Carbapenem-Resistant Gram-Negative Bacilli in an In Vitro Chemostat Model

Cited by 7 publications

References 16 publications

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

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