ME1228 is a new cephalosporin with an iminocarboxymethyl moiety on the acyl side chain and a novel pyridiniumthiomethyl group at position 3 of the bicyclic ring. Its activity was compared with those of ceftazidime, imipenem, piperacillin, and gentamicin. ME1228 inhibited most members of the family Enterobacteriaceae, except for some Enterobacter spp. and Citrobacter freundii, at less than or equal to 0.25 micrograms/ml, and it inhibited gentamicin- and piperacillin-resistant isolates. It had MICs for Pseudomonas aeruginosa between 1 and 32 micrograms/ml, comparable to those of ceftazidime, and it inhibited piperacillin- and gentamicin-resistant isolates. Most group A, B, C, and G streptococci and Streptococcus pneumoniae were inhibited by less than or equal to 0.25 micrograms/ml. Enterococci and listeriae were resistant (MICs, 64 to 128 micrograms/ml). The MICs for staphylococci were 4 to 8 micrograms/ml, and methicillin-resistant Staphylococcus aureus was resistant. There was a minimal inoculum effect and no effect of the medium. ME1228 was not hydrolyzed by TEM-1, TEM-2, SHV-1, and S. aureus plasmid beta-lactamases and was stable against hydrolysis by Richmond-Sykes type 1a, 1c, 1d, and IV chromosomal beta-lactamases. It was hydrolyzed by TEM-3 and Xanthomonas maltophilia beta-lactamases. Overall, ME1228 had activity comparable or superior to that of ceftazidime.