Ro 13-9904, a long-acting broad-spectrum cephalosporin: in vitro and in vivo studies

Abstract

Ro 13-9904, a new parenteral cephalosporin, was found to have high in vitro activity against Enterobacteriaceae and other gram-negative bacteria, including various isolates resistant to cefuroxime, cefamandole, cefoxitin, and cefazolin. It showed promising activity against Pseudomonas aeruginosa. Although inhibitory against Staphylococcus aureus at concentrations readily achievable in plasma, it was less potent against this pathogen than cefamandole, cefazolin, or cefuroxime.Isolates of Streptococcus faecalis were uniformly resistant to all the cephalosporins tested. Ro 13-9904 was more active than cefotaxime against Proteus mirabilis, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae, but less active against S. aureus. Ro 13-9904 was stable to various types of f,-lactamases. Its therapeutic efficacy against experimental septicemias in mice was equal to or slightly superior to that of cefotaxime and SCE-1365 when the antibiotics were administered in repeated subcutaneous doses after bacterial challenge. Cefoperazone, and particularly cefamandole nafate, cefazolin, and mezlocillin were less effective. Although structurally related to cefotaxime and SCE-1365, Ro 13-9904 was found to differ from them in one important respect, namely, in having a long duration of action; this was observed with single-dose treatment given before bacterial challenge. Its broad spectrum of activity coupled with favorable pharmacokinetic properties make Ro 13-9904 a promising compound for clinical studies.Since the development of cephalothin and cephaloridine, the first cephalosporins on the market, the antibacterial potency of this attractive class of antibiotics has undergone profound improvement over the years. The newest semi-

Failure of beta-lactam antibiotics and marked efficacy of fluoroquinolones in treatment of murine Yersinia pseudotuberculosis infection

“…Here, the 3-lactam treatments administered at usual doses (20 mg/kg) (2,4,26,27,29) demonstrated less efficacy than classic treatments such as gentamicin or doxycycline. Therefore, a treatment can be considered really successful when administration of the drug leads to a decrease in the growth kinetics curves and not merely to a significant difference between treated and nontreated groups of mice.…”

Pharmacokinetic study of sulbactomax

“…Ceftriaxone is a broad spectrum antibiotic that displays potent activity against gram-positive and gram-negative bacteria (Angehrn et al, 1980). The pharmacokinteic parameters of ceftriaxone and sulbactam alone has been reported in several literatures (Foulds et al, 1983;Patel et al, 1981;Meyers et al, 1983).…”

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis

“…Microbiol., in press); and (ii) altered platelet aggregation and bleeding disturbances at the maximal dosages necessary for the therapy of central nervous system infections (29). The in vitro activities of ceftriaxone and cefotaxime are nearly identical (1,14,17,28,39;Scheld et al, in press), including the activities against the major meningeal pathogens, and both of these agents have proven efficacy in the therapy of meningitis in humans (2,6,8,12,29,40). The clinical experience with ceftriaxone exceeds that with cefotaxime alone for this disease.…”

“…Ceftriaxone (RO13-9904) is a new third-generation cephalosporin with excellent in vitro activity against all major meningeal pathogens (1,14,17,28,39; Scheld, Rocha, Sande, and Bryan, Am. J.…”