In vitro and in vivo evaluation of MDL 19,592, an oral cephalosporin.
MDL 19,592 is a new semisynthetic cephalosporin with a good therapeutic potential against Gram-positive bacterial infections when administered orally or parenterally. In the oral treatment of benzylpenicillin-resistant Staphylococcus aureus infections in mice, MDL 19,592 was superior to cephalexin, cephradine, cefaclor, cefadroxil and cefroxadine. These in vivo results reflect the in vitro superiority expressed by MDL 19,592 over the other oral cephalosporins against staphylococci. Additionally, MDL 19,592 orally was superior to cefazolin and cephalothin administered subcutaneously and to a number of penicillinase-resistant penicillins given orally or subcutaneously in the treatment of S. aureus mouse infections. MDL 19,592 killed S. aureus cells at the same or faster rate than did cephalexin or cephradine. As compared to cephalexin, MDL 19,592 was marginally superior in vitro against Streptococcus pyogenes and Streptococcus pneumoniae. In vivo, MDL 19,592 was significantly the more effective of the two against S. pyogenes and marginally more effective against S. pneumoniae. Against Gram-negative organisms, with the exception of Haemophilus influenzae, cephalexin was the more potent of the two antibiotics both in vitro and in vivo. Administered orally to mice, MDL 19,592 was absorbed as rapidly as cephalexin with both drugs attaining similar concentrations in the blood. MDL 19,592, like cephalexin, was minimally bound by mouse serum.
D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001798:Blood Proteins / Q000378:metabolism; D002511:Cephalosporins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D010405:Penicillinase / Q000378:metabolism; D013329:Structure-Activity Relationship
D001798:Blood Proteins; D002511:Cephalosporins; C039872:MDL 19592; D010405:Penicillinase