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Siderophore cephalosporin

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https://www.readbyqxmd.com/read/29318906/cefiderocol-a-novel-siderophore-cephalosporin
#1
Justin J Choi, Matthew W McCarthy
The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including β-lactam- and carbapenem-resistant organisms. Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of β-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms...
January 10, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29311072/pharmacokinetics-safety-and-tolerability-of-cefiderocol-a-novel-siderophore-cephalosporin-for-gram-negative-bacteria-in-healthy-subjects
#2
Yutaka Saisho, Takayuki Katsube, Scott White, Hiroyuki Fukase, Jingoro Shimada
Cefiderocol is a novel parenteral siderophore cephalosporin that shows potent efficacy against various Gram-negative bacteria, including carbapenem-resistant strains, in vitro and in preclinical models of infection. The aim of the present study was to evaluate the pharmacokinetics (PK), safety, and tolerability of cefiderocol after both single and multiple dosing by intravenous infusion over 60 min in healthy adult subjects. A single-ascending-dose study at doses of 100, 250, 500, 1000, and 2000 mg was conducted in 40 healthy Japanese males and females (six active and two placebo per cohort)...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29158270/in-vitro-activity-of-the-siderophore-cephalosporin-cefiderocol-against-carbapenem-non-susceptible-and-multidrug-resistant-isolates-of-gram-negative-bacilli-collected-worldwide-in-2014-2016
#3
Meredith A Hackel, Masakatsu Tsuji, Yoshinori Yamano, Roger Echols, James A Karlowsky, Daniel F Sahm
The in vitro activity of the investigational siderophore cephalosporin, cefiderocol (formerly S-649266), was determined against a 2014-2016, 52-country, worldwide collection of clinical isolates of carbapenem-non-susceptible Enterobacteriaceae (n=1,022), multidrug-resistant (MDR) Acinetobacter baumannii (n=368), MDR Pseudomonas aeruginosa (n=262), Stenotrophomonas maltophilia (n=217), and Burkholderia cepacia (n=4) using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method...
November 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29111435/pharmacodynamics-of-cefiderocol-a-novel-siderophore-cephalosporin-explored-in-a-pseudomonas-aeruginosa-neutropenic-murine-thigh-model
#4
Islam M Ghazi, Marguerite L Monogue, Masakatsu Tsuji, David P Nicolau
BACKGROUND: Cefiderocol is a siderophore cephalosporin that displays potent in vitro activity against multi-drug resistant (MDR) Gram-negative bacteria. We aimed to describe cefiderocol's pharmacokinetics, pharmacodynamics, and 24-hour efficacy using dose-ranging methods in the neutropenic murine thigh infection model. METHODS: Infection was established in neutropenic mice (administered cyclophosphamide 150 mg/kg and 100 mg/kg 4 and 1 days prior to inoculation respectively) with 8 Pseudomonas aeruginosa isolates (MIC range: 0...
October 27, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29061741/in-vitro-antibacterial-properties-of-cefiderocol-a-novel-siderophore-cephalosporin-against-gram-negative-bacteria
#5
Akinobu Ito, Takafumi Sato, Merime Ota, Miki Takemura, Toru Nishikawa, Shinsuke Toba, Naoki Kohira, Satoshi Miyagawa, Naoki Ishibashi, Shuhei Matsumoto, Rio Nakamura, Masakatsu Tsuji, Yoshinori Yamano
Cefiderocol (CFDC, S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species including carbapenem-resistant strains of Enterobacteriaceae and non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP 3) of Enterobacteriaceae and non-fermenting bacteria similar to ceftazidime...
October 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038272/population-pharmacokinetic-analysis-of-cefiderocol-a-parenteral-siderophore-cephalosporin-in-healthy-subjects-subjects-with-varying-renal-function-and-patients-with-complicated-urinary-tract-infection-or-acute-uncomplicated-pyelonephritis
#6
Nao Kawaguchi, Takayuki Katsube, Roger Echols, Toshihiro Wajima
Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria including carbapenem-resistant strains. The aim of this study is to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with varying renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens, and to calculate the fraction of time during the dosing interval where the free drug concentration in plasma exceeds the minimum inhibitory concentration (MIC) (fT>MIC)...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#7
REVIEW
H Wright, R A Bonomo, D L Paterson
BACKGROUND: Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms...
October 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28748397/activity-of-the-novel-siderophore-cephalosporin-cefiderocol-against-multidrug-resistant-gram-negative-pathogens
#8
J Dobias, V Dénervaud-Tendon, L Poirel, P Nordmann
The novel siderophore cephalosporin cefiderocol (S-649266) with potent activity against Gram-negative pathogens was recently developed (Shionogi & Co., Ltd.). Here, we evaluated the activity of this new molecule and comparators against a collection of previously characterized Gram-negative isolates using broth microdilution panels. A total of 753 clinical multidrug-resistant Gram-negative isolates collected from hospitals worldwide were tested against cefiderocol and antibiotic comparators (ceftolozane-tazobactam [CT], meropenem [MEM], ceftazidime [CAZ], ceftazidime-avibactam [CZA], colistin [CST], aztreonam [ATM], amikacin [AMK], ciprofloxacin [CIP], cefepime [FEP], and tigecycline [TGC]) for their susceptibility...
December 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28668680/antimicrobial-activities-of-lcb10-0200-a-novel-siderophore-cephalosporin-against-the-clinical-isolates-of-pseudomonas-aeruginosa-and-other-pathogens
#9
Sang-Hun Oh, Hee-Soo Park, Hye-Shin Kim, Jeong-Yul Yun, Kyuman Oh, Young-Lag Cho, Jin-Hwan Kwak
Infections caused by multidrug-resistant bacteria, including Pseudomonas aeruginosa, are threatening public health worldwide. Therefore, a novel antibacterial agent is needed to treat these infections. Here, we investigated the in vitro and in vivo activities of a novel siderophore-conjugated cephalosporin, LCB10-0200, against the clinical isolates of Gram-negative bacteria, including multidrug-resistant P. aeruginosa. In vitro susceptibility to LCB10-0200 was assessed by performing a two-fold agar dilution method, as described by the Clinical and Laboratory Standards Institute...
June 28, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28630181/in-vitro-activity-of-the-siderophore-cephalosporin-cefiderocol-against-a-recent-collection-of-clinically-relevant-gram-negative-bacilli-from-north-america-and-europe-including-carbapenem-nonsusceptible-isolates-sidero-wt-2014-study
#10
Meredith A Hackel, Masakatsu Tsuji, Yoshinori Yamano, Roger Echols, James A Karlowsky, Daniel F Sahm
Cefiderocol (formerly S-649266) is an investigational siderophore cephalosporin. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) was prepared according to the Clinical and Laboratory Standards Institute (CLSI) protocol and used to perform broth microdilution testing of cefiderocol against a 2014-2015 collection of clinical isolates of Gram-negative bacilli from North America (n = 4,239) and Europe (n = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC90s) were 0...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630178/efficacy-of-cefiderocol-against-carbapenem-resistant-gram-negative-bacilli-in-immunocompetent-rat-respiratory-tract-infection-models-recreating-human-plasma-pharmacokinetics
#11
Shuhei Matsumoto, Christine M Singley, Jennifer Hoover, Rio Nakamura, Roger Echols, Stephen Rittenhouse, Masakatsu Tsuji, Yoshinori Yamano
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 (Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae) in immunocompetent-rat respiratory tract infection models recreating plasma pharmacokinetics (PK) profiles in healthy human subjects. A total of 6 clinical isolates (1 cephalosporin-susceptible P...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438934/susceptibility-of-imipenem-susceptible-but-meropenem-resistant-blaimp-6-carrying-enterobacteriaceae-to-various-antibacterials-including-the-siderophore-cephalosporin-cefiderocol
#12
LETTER
Sachi Kanazawa, Takafumi Sato, Naoki Kohira, Tsukasa Ito-Horiyama, Masakatsu Tsuji, Yoshinori Yamano
No abstract text is available yet for this article.
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28410852/cefiderocol-mic-quality-control-ranges-in-iron-depleted-cation-adjusted-mueller-hinton-broth-using-a-clsi-m23-a4-multi-laboratory-study-design
#13
Michael D Huband, Akinobu Ito, Masakatsu Tsuji, Helio S Sader, Kelley A Fedler, Robert K Flamm
Cefiderocol (formerly S-649266) is a new catechol-substituted parenteral siderophore cephalosporin with potent in vitro antibacterial activity against Gram-negative isolates including multidrug-resistant strains. A recent study following CLSI M23-A4 quality control guidelines established cefiderocol MIC QC ranges against Escherichia coli ATCC 25922 (0.06-0.5 μg/mL) and Pseudomonas aeruginosa ATCC 27853 (0.06-0.5 μg/mL).
March 23, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28369471/activity-of-cefiderocol-s-649266-against-carbapenem-resistant-gram-negative-bacteria-collected-from-inpatients-in-greek-hospitals
#14
Matthew E Falagas, Tilemachos Skalidis, Konstantinos Z Vardakas, Nicholas J Legakis
Background: Cefiderocol (S-649266), a siderophore cephalosporin, utilizes a novel mechanism of entry into the periplasmic space of Gram-negative bacteria and is broadly stable to ESBLs and carbapenemases. Methods: A collection of carbapenem-resistant Gram-negative bacteria isolated from clinical specimens in 18 Greek hospitals was tested for susceptibility to cefiderocol, meropenem, ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam, amikacin, ciprofloxacin, colistin and tigecycline...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27874971/cefiderocol-a-siderophore-cephalosporin-for-gram-negative-bacterial-infections-pharmacokinetics-and-safety-in-subjects-with-renal-impairment
#15
Takayuki Katsube, Roger Echols, Juan Camilo Arjona Ferreira, Heidi K Krenz, Jolene Kay Berg, Christopher Galloway
Cefiderocol, a new injectable siderophore cephalosporin antibiotic, has promising in vitro and in vivo activity against Gram-negative bacteria including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Cefiderocol is mainly renally eliminated. The pharmacokinetics and safety of cefiderocol in subjects with renal impairment were assessed following a single 1000-mg intravenous 1-hour infusion of cefiderocol. Subjects with mild, moderate, or severe renal impairment and end-stage renal disease (ESRD) requiring hemodialysis were compared with demographically (age, body mass index, and sex) matched healthy subjects with normal renal function...
May 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27795374/pharmacokinetic-pharmacodynamic-modeling-and-simulation-of-cefiderocol-a-parenteral-siderophore-cephalosporin-for-dose-adjustment-based-on-renal-function
#16
Takayuki Katsube, Toshihiro Wajima, Toru Ishibashi, Juan Camilo Arjona Ferreira, Roger Echols
Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (Tf>MIC) for an MIC range of 0...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27736756/siderophore-cephalosporin-cefiderocol-utilizes-ferric-iron-transporter-systems-for-antibacterial-activity-against-pseudomonas-aeruginosa
#17
Akinobu Ito, Toru Nishikawa, Shuhei Matsumoto, Hidenori Yoshizawa, Takafumi Sato, Rio Nakamura, Masakatsu Tsuji, Yoshinori Yamano
Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the third-position side chain. The in vitro activity of cefiderocol against Pseudomonas aeruginosa was enhanced under iron-depleted conditions, whereas that of ceftazidime was not affected. The monitoring of [thiazole-14C]cefiderocol revealed the increased intracellular accumulation of cefiderocol in P. aeruginosa cells incubated under iron-depleted conditions compared with those incubated under iron-sufficient conditions...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27512687/imaging-bacteria-with-radiolabelled-quinolones-cephalosporins-and-siderophores-for-imaging-infection-a-systematic-review
#18
S Auletta, F Galli, C Lauri, D Martinelli, I Santino, Alberto Signore
Bacterial infections are still one of the main causes of patient morbidity and mortality worldwide. Nowadays, many imaging techniques, like computed tomography or magnetic resonance imaging, are used to identify inflammatory processes, but, although they recognize anatomical modifications, they cannot easily distinguish bacterial infective foci from non bacterial infections. In nuclear medicine, many efforts have been made to develop specific radiopharmaceuticals to discriminate infection from sterile inflammation...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27139465/stability-of-novel-siderophore-cephalosporin-s-649266-against-clinically-relevant-carbapenemases
#19
Tsukasa Ito-Horiyama, Yoshikazu Ishii, Akinobu Ito, Takafumi Sato, Rio Nakamura, Norio Fukuhara, Masakatsu Tsuji, Yoshinori Yamano, Keizo Yamaguchi, Kazuhiro Tateda
To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies (kcat/Km) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM(-1) s(-1), respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM.
July 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27025519/microarray-evaluation-of-antimicrobial-resistance-and-virulence-of-escherichia-coli-isolates-from-portuguese-poultry
#20
Nuno Mendonça, Rui Figueiredo, Catarina Mendes, Roderick M Card, Muna F Anjum, Gabriela Jorge da Silva
The presence of antimicrobial resistance and virulence factors of 174 Escherichia coli strains isolated from healthy Portuguese Gallus gallus was evaluated. Resistance profiles were determined against 33 antimicrobials by microbroth dilution. Resistance was prevalent for tetracycline (70%) and ampicillin (63%). Extended-spectrum beta-lactamase (ESBL) phenotype was observed in 18% of the isolates. Multidrug resistance was found in 56% of isolates. A subset of 74 isolates were screened by DNA microarrays for the carriage of 88 antibiotic resistance genes and 62 virulence genes...
2016: Antibiotics
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