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Siderophore cephalosporin

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 3(rd)-position side chain. The in vitro activity of cefiderocol against Pseudomonas aeruginosa was enhanced in the iron-depleted condition where that of ceftazidime was not affected. The monitoring of [Thiazole-(14)C]-cefiderocol revealed the increased intracellular accumulation of cefiderocol in the P. aeruginosa cells incubated under iron-depleted condition compared with those incubated under iron-sufficient condition...
October 10, 2016: Antimicrobial Agents and Chemotherapy
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
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
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
Akinobu Ito, Naoki Kohira, Samuel K Bouchillon, Joshua West, Stephen Rittenhouse, Helio S Sader, Paul R Rhomberg, Ronald N Jones, Hidenori Yoshizawa, Rio Nakamura, Masakatsu Tsuji, Yoshinori Yamano
OBJECTIVES: S-649266 is a parenteral siderophore cephalosporin antibiotic with a catechol moiety on its side chain. The in vitro antimicrobial activity of S-649266 against non-fermenting Gram-negative bacteria was evaluated and compared with the activities of meropenem, levofloxacin, cefepime, ceftazidime and piperacillin/tazobactam. METHODS: MIC values of S-649266 were determined in Mueller-Hinton broth or Iso-Sensitest broth supplemented with apo-transferrin. RESULTS: S-649266 showed potent in vitro activity against the non-fermenting Gram-negative bacteria Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, including MDR strains such as carbapenem-resistant A...
March 2016: Journal of Antimicrobial Chemotherapy
Naoki Kohira, Joshua West, Akinobu Ito, Tsukasa Ito-Horiyama, Rio Nakamura, Takafumi Sato, Stephen Rittenhouse, Masakatsu Tsuji, Yoshinori Yamano
S-649266 is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Two sets of clinical isolate collections were used to evaluate the antimicrobial activity of S-649266 against Enterobacteriaceae. These sets included 617 global isolates collected between 2009 and 2011 and 233 β-lactamase-identified isolates, including 47 KPC-, 49 NDM-, 12 VIM-, and 8 IMP-producers. The MIC90 values of S-649266 against the first set of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae isolates were all ≤1 μg/ml, and there were only 8 isolates (1...
February 2016: Antimicrobial Agents and Chemotherapy
Farzan Modarresi, Omid Azizi, Mohammad Reza Shakibaie, Mohammad Motamedifar, Ellahe Mosadegh, Shahla Mansouri
Acinetobacter baumannii is an important source of infections in intensive care units (ICUs) of our hospitals in Kerman, Iran and the most frequently isolated strains produce biofilm. There is a little information about role of iron (Fe) levels on acyl homoserine lactone (AHL) production and biofilm formation in this microorganism. In the present study, we investigated the influence of iron-III limitation on AHL, siderophore, catechol and virulence factors in the biofilm forming clinical strains of A. baumannii...
2015: Virulence
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