In vitro evaluation of BO-3482, a novel dithiocarbamate carbapenem with activity against methicillin-resistant staphylococci

BO-3482, a dithiocarbamate carbapenem, inhibited clinical isolates of methicillin-resistant staphylococci (MRS) at 6.25 microg/ml (MIC at which 90% of isolates tested are inhibited [MIC90]), while the MIC90 of imipenem was > 100 microg/ml. BO-3482 was generally less active than imipenem against methicillin-susceptible Staphylococcus aureus, streptococci, enterococci, and gram-negative bacteria, although BO-3482 showed better activity (MIC90) than imipenem against Enterococcus faecium, Haemophilus influenzae, Proteus mirabilis, and Clostridium difficile. The affinities (50% inhibitory concentrations) of BO-3482 for penicillin-binding protein (PBP) PBP 2' of MRS and PBP 5 of E. faecium (both PBPs have low affinities for ordinary Beta-lactam Antibiotics) were 3.8 and 20 microg/ml, respectively, reflecting the greater activity of BO-3482 against MRS than against E. faecium.