Comparative in-vitro activity of Sch 34343, a new penem antibiotic

Using an agar dilution technique we examined the in-vitro activity of Sch 34343 against 485 clinical bacterial isolates. Ampicillin, mezlocillin, cefuroxime, cefotaxime, cefotetan, ceftazidime, ceftriaxone, imipenem (N-formimidoyl thienamycin) and gentamicin were used for comparison. Sch 34343 exhibited activity against all species tested, excepting Pseudomonas aeruginosa and Pseudomonas species. Unlike many newer beta-lactams, Sch 34343 was highly active against Gram-positive species. It was consistently active against the Enterobacteriaceae, with MIC50 and MIC90 being usually closely similar, as were results with two inoculum sizes (104 and 106 cfu). This, together with its activity against strains resistant to many other beta-lactam agents, suggested high stability to beta-lactamases. Sch 34343 was the most active compound tested against Bacteroides fragilis. In tests of combined bacteriostatic action with gentamicin no synergy was seen. It had bactericidal action in broth culture, against sensitive strains of E. coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus faecalis. It showed good stability in aqueous solution and serum at low temperatures at pH values in the physiological range, and was moderately stable at 37 degrees C. Binding in human plasma was 72%. We concluded that Sch 34343 is a highly promising agent with a broad spectrum of activity making it potentially suitable as monotherapy for patients with infection of undetermined bacterial aetiology, particularly if Bact. fragilis is a possible pathogen.