New anti-MRSA cephalosporins with a basic aminopyridine at the C-7 position

Cho, Aesop; Glinka, Tomasz; Ludwikow, M.; Fan, Andrew T.; Wang, Michael; Hecker, Scott J.

doi:10.1016/s0960-894x(00)00603-x

Cited by 18 publications

(2 citation statements)

References 14 publications

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“…It should be noted that S-3578 is soluble in water at more than 100 mg/ml (26). This water solubility is a great advantage because most anti-MRSA cephalosporins have been reported elsewhere to be insoluble in water (4,9). The pharmacokinetic profile of S-3578 in mice is similar to that of cefepime, and S-3578 shows good therapeutic efficacy in murine models of infection by MRSA, penicillin-resistant S. pneumoniae, or P. aeruginosa (M. Tsuji, M. Takema, H. Miwa, J. Shimada, and S. Kuwahara, submitted for publication).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of S-3578, a New Broad-Spectrum Cephalosporin Active against Methicillin-Resistant Staphylococci

Fujimura

Yamano

Yoshida

et al. 2003

Antimicrob Agents Chemother

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The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 g/ml for methicillinresistant Staphylococcus aureus (MRSA) and 2 g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 g/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log 10 decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 10 9 cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC 90 of 1 g/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation.

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of S-3578, a New Broad-Spectrum Cephalosporin Active against Methicillin-Resistant Staphylococci

Fujimura

Yamano

Yoshida

et al. 2003

Antimicrob Agents Chemother

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“…82 Later, Berkesel reported low yields in the DPPA-mediated transformation of cyclohexane-1,2-dicarboxylic acid. 45 In 2001 and 2003, pyridine-2,6-and -3,5-dicarboxylic acids were engaged in such desymmetrizations by Cho 83 and Nakayama 84 with moderate yields, 45% and 46% respectively. Therefore, we can divide the substrates used in this approach into two classes depending on if (1) both carboxylic acids are close from each other or (2) carboxylic acids are spaced by a rigid linker.…”

Section: Introductionmentioning

confidence: 99%