A new carbapenem, biapenem, its in vitro activity, affinity to bacterial PBPs, and stability to human renal dehydropeptidase-I

Abstract

Eighty percent minimum inhibitory concentrations (MIC₈₀) of biapenem (BIPM) were 0.39, 6.25, 3.13, ≤0.013, 0.025, ≤0.013, 6.25, >100, 0.2, 0.2, 0.39, 1.56, 6.25, 1.56, 0.78, 0.39, 0.39, 1.56, 6.25, >100, 0.78, 6.25 and 0.39μg/ml against 13 to 50 clinical isolates of Staphylococcus aureus, methicillin-resistant S. aureus, coagulase-negative Staphylococci, Streptococcus pyogenes, βStreptococci, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli CS2 (R⁺), Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Morganella morganii, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, Pseudomonas cepacia, Xanthomonas maltophilia, Acinetobacter calcoaceticus, ampicillin-resistant Haemophilus influenzae and Bacteroides frangilis, respectively.
Biapenem (BIPM) was very stable against allβ-lactamases tested and also showed potent first-order inhibitory activities (i.e. small Ki values), which were stronger than those of imipenem (IPM) against both PCase and CEPase.
BIPM manifested higher binding affinity to PBP 1 of S. aureus, and PBP 2 of E. coli, S.marcescens, and P.aeruginosa than IPM.
BIPM manifested good synergy with mouse cultured macrophages in live E. coli phagocytosis atconcentrations of morer than 1/8 the MIC of BIPM.
The stability of BIPM to human renal dehydoropeptidase-I (DHP-I) was compared with those ofother carbapenems; IPM, panipenem and meropenem. BIPM was the most stable to DHP-I in carbapenems tested.