[RU 51807 (cefpodoxime proxetil). In vitro and in vivo antibacterial activity of a new orally administered active cephalosporin].
Cefpodoxime proxetil (RU 51807) is an enterally absorbed ester prodrug which is rapidly cleaved in vivo after oral administration, with release of the active free acid metabolite cefpodoxime. The in vitro antibacterial activity of the sodium salt of cefpodoxime (RU 51746) against approximately 800 clinical isolates was evaluated comparatively with other orally active beta-lactams. RU 51746 was found to be active against enterobacteria normally susceptible to third generation cephalosporins, with MIC50 values ranging from 0.02 mg/l (Providencia sp) to 5 mg/l (C. freundii). RU 51746 was also active against H. influenzae, including beta-lactamase producing strains (MIC50 0.04 mg/l), oxa-S S. aureus (2,5), beta-hemolytic streptococci (0.05) and S. pneumoniae (0.002). Oxa-R staphylococci and P. aeruginosa were resistant to RU 51746 (MIC50 greater than 40 mg/l for both organisms). The antibacterial activity of RU 51746 was bactericidal in nature and independent from test conditions. The molecule was stable to all the beta-lactamases studied, with the exception of cefuroximase (type Ic). RU 51746 exhibited no strong inhibitory effects on these enzymes, except with Enterobacter P99 (type Ia). A good correlation was found between in vivo activity of RU 51807 and in vitro activity of RU 51746. Cefpodoxime proxetil was found to be more effective than cefaclor in mice with experimental septicemia caused by various streptococci, with a DP50 ratio in the 10-100 range. This advantage was again evidenced for septicemias due to various enterobacteria. In contrast, cefaclor proved more effective in experimental staphylococcus infections. In mice with experimental pneumonia, cefpodoxime proxetil caused sharp falls in K. pneumoniae lung counts. Six days after induction of the infection, 60% of animals under cefpodoxime proxetil had sterile lungs, versus 25% of animals under amoxicillin.
Chantot
J F
JF
Centre de Recherche Roussel-Uclaf, Romainville, France.
Mauvais
P
P
D000818:Animals; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004755:Enterobacteriaceae / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects*; D007710:Klebsiella Infections / Q000188:drug therapy; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013210:Staphylococcus / Q000187:drug effects*; D013290:Streptococcal Infections / Q000188:drug therapy; D001618:beta-Lactamases / Q000032:analysis; D000097627:Cefpodoxime Proxetil
D015296:Ceftizoxime; D001618:beta-Lactamases; D000097627:Cefpodoxime Proxetil
RU 51807 (cefpodoxime proxétil). Evaluation de l'activité antibactérienne in vitro et in vivo d'une nouvelle céphalosporine active par voie orale.