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.