TOC-39, A NOVEL PARENTERAL BROAD-SPECTRUM CEPHALOSPORIN WITH EXCELLENT ACTIVITY AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS

TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for antibacterial activity against various clinically isola ted strains. TOC-39 had excellent activity, stronger than that of meth icillin, oxacillin, the cephalosporins tested, imipenem, gentamicin, m inocycline, tobramycin, ofloxacin, and ciprofloxacin against methicill in-resistant Staphylococcus aureus (MRSA) and had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin for 90% of the strains tested were 3.13 and 1.56 mu g/ml, respectively). Against Ente rococcus faecalis strains, which are resistant to cephalosporins, TOC- 39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus, coagulase-negative Staphylococcus spp., and Streptococcus p neumoniae, TOC-39 was twice as active as or more active than cefotiam, ceftazidime, flomoxef, and cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam, ceftazidime, and flomoxef and was si milar to cefpirome. In addition, the activity of TOC-39 was equal to o r greater than that of cefotiam, ceftazidime, flomoxef, and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella pneumonia e, Proteus mirabilis, and Morganella morganii. In terms of bactericida l effect against MRSA, TOC-39 was superior to vancomycin. No mutant re sistant to TOC-39 or vancomycin was obtained from susceptible MRSA str ains. In murine systemic infection models, TOC-39 showed potent activi ty against S. aureus and E. coli. Against highly MRSA, the activity of TOC-39 was comparable to that of vancomycin.