Sch 29482, a new oral penem: comparative in-vitro activity, -lactamase stability and inhibition

Abstract

Microdilution susceptibility tests were performed with 527 clinical isolates collected from seven geographically separate institutions: 60% of the strains demonstrated some β -lactamase activity, as detected by nitrocefin hydrolysis. Sch 29482 (SCH) was very resistant to hydrolysis by six different β -lactmäases and was effective against all β -lactamase-producing isolates, except Pseudomonas aeruginosa . SCH was more effective than the oral agents, amoxycillin, cephalexin, or cefaclor and the parenterally administered β -lactams, cephalothin or cefamandole. Its spectrum of activity was most similar to that of cefotaxime. SCH had no activity against Pseudomonas species other than Ps. cepacia and Ps. acidovorans . It was minimally active against Streptococcus faecalis and methicillin-resistant Staphylococcus aureus , but very active against methicillin-susceptible Staph. aureus, Str. pyogenes, Str. pneumoniae, Neisseria meningitidis, N. gonorrhoeae, and Haemophilus influenzae . All but 3 of 218 Enterobacteriaceae strains were inhibited by 80 mg/l. In-vitro activity of SCH was markedly diminished when tested in the presence of 50% human serum. In addition to being β -lactamase stable, SCH markedly inhibited the activity of Type I β -lactamase and partially inhibited Type III (TEM 1 and TEM 2) enzymes.