vitro antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic. Antimicrob. Agents Chemother

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, san-fetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma. Sanfetrinem cilexetil is the oral prodrug of sanfetrinem, the first in a series of novel tricyclic b-lactam compounds, the trinems (Fig. 1). Previous reports have demonstrated that san-fetrinem has high stability to many b-lactamases and to human renal dehydropeptidase I and has a broad spectrum of activity against gram-positive and gram-negative bacteria including penicillin-resistant Streptococcus pneumoniae (PRSP) (2, 8–10, 13). In this study, we evaluated the in vivo activities of san-fetrinem cilexetil and compared them with those of cefdinir and amoxicillin. Sanfetrinem cilexetil and sanfetrinem were supplied by Glaxo Wellcome SpA (Verona, Italy). The other antibiotics were provided by the indicated manufacturers, as follows: imipenem, Banyu Pharmaceutical Co. (Tokyo, Japan); faro-penem, Suntory Co. (Osaka, Japan); cefdinir and amoxicillin