In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin

Abstract

clinical isolates to R-3746 was determined by the agar dilution method. Ninety percent or more of pathogens such as Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, indole-positive and indole-negative Proteus spp., Providencia rettgeri, and Haemophilus influenzae were inhibited at concentrations ranging from .0.01 to 1.56 ,ug/ml. Furthermore, at a concentration of 3.13 ,ug/ml, 50% or more of Staphylococcus epidermidis, Morganella morganii, Citrobacterfreundii, and Serratia marcescens strains were also inhibited. Pseudomonas aeruginosa and Xanthomonas maltophilia were resistant to R-3746.The activity of R-3746 was scarcely influenced by several growth conditions. R-3746 was highly resistant to hydrolysis by Il-lactamases derived from various species of bacteria. Killing-curve studies demonstrated bactericidal activity of R-3746 at concentrations above the MIC. R-3746 showed high affinity for penicillinbinding proteins 1, 3, and 4 of Staphylococcus aureus and 1A, 1l$s, and 3 of Escherichia coli. Systemic infections in mice caused by various pathogens, including j3-lactamase-producing strains, responded well to therapy with oral doses of CS-807.Various oral cephem antibiotics having relatively broad antibacterial spectra have been developed and used worldwide (2, 3,15,18,19,34 Fig. 1.The present report deals with the in vitro antibacterial activity of R-3746 together with the therapeutic effect of CS-807 on systemic infections in mice compared with cefaclor, amoxicillin, cefixime, and T-2588 (T-2525).* Corresponding author. MATERIALS AND METHODSChemicals. CS-807 and R-3746 were prepared by Sankyo Co., Ltd., Tokyo, Japan. The other antibiotics were gifts: penicillin G, amoxicillin, and methicillin from Banyu Pharmaceutical Co., Ltd., Tokyo, Japan; cephaloridine from Nihon Glaxo Co., Ltd., Tokyo, Japan; cefaclor from Shionogi & Co., Ltd., Osaka, Japan; cefixime from Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan; and T-2588 and T-2525 from Toyama Chemical Co., Ltd., Tokyo, Japan. All antibiotics were prepared daily with distilled water to the desired concentrations. '4C-labeled penicillin G (potassium 6-phenyl [1-_4C]

Synthesis, characterization and antimicrobial studies of imine derivatives of amoxicillin

“…Very recently, we have reported the synthesis of novel xanthene based imine derivatives showing excellent antibacterial activity [18]. Inspired with biological activities possessed by imines [19][20][21][22][23] and amoxicillin, an endeavor was made to manufacture novel imine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) of amoxicillin by condensing it with different aldehydes and ketones. The novel amoxicillin imine derivatives were characterized well by different spectroscopic techniques and screened for antimicrobial activities.…”

“…Novel amoxicillin imine compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) have been screened for in vitro antimicrobial or antibacterial activities (Table 2). Examining the data of inhibition zone against Pseudomonas aeruginosa, it is observed that almost all the new compounds showed antibacterial activities more than the parent drug amoxicillin.…”

“…Commercially available amoxicillin trihydrate was coupled with different carbonyl compounds in absolute ethanol as solvent. The reaction mixtures were poured in cold water to afford precipitates of the imine derivative (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The progress of the reaction was monitored by thin layer chromatography until the complete consumption of starting material.…”

“…All the synthetic derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were screened for antimicrobial activities using disc diffusion method by measuring the inhibition zone in comparison with the standard drug, amoxicillin. Antimicrobial activity of the compounds was determined against bacterial strains including Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli which were isolated from urinary tract infections, surgical theaters, nose swab and infected wounds respectively in Muller Hinton agar.…”

“…β-lactam drugs are usually obtained from fungi or molds [4]. Though most of the β-lactam antibiotics are active against gram positive bacteria, yet there are some recently developed drug like cephalosporin [5] etc. which serve as broad spectrum antibiotics both against gram positive and gram negative bacteria [6,7].…”