In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase I

Abstract

SM-7338, a new carbapenem antibiotic, was demonstrated to have potent antibacterial activity against a broad spectrum of aerobes, including Staphylococcus aureus, beta-hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria spp., members of the family Enterobacteriaceae, Pseudomonas spp., and gram-positive and gram-negative anaerobes in a collection of 1,102 unselected clinical isolates. At a concentration of 0.5 micrograms/ml, SM-7338 inhibited 90% of these strains. The spectrum of activity of ceftazidime and cefotaxime was more limited, and many of the Enterobacteriaceae and Pseudomonas spp. were resistant to these agents, piperacillin, or gentamicin. A collection of ofloxacin-resistant strains was inhibited by SM-7338 or imipenem at 4 micrograms/ml. SM-7338 was more active than metronidazole and clindamycin against anaerobes. Of the carbapenems, imipenem had greater activity against staphylococci but SM-7338 was much more active against Haemophilus, Branhamella, and Neisseria spp. and all genera of Enterobacteriaceae tested. The MIC of SM-7338 for 90% of these strains ranged from less than or equal to 0.008 to 0.13 micrograms/ml. When tested against 124 strains of Pseudomonas aeruginosa, SM-7338 inhibited 76% at 0.5 microgram/ml but imipenem inhibited only 15% at this concentration. Both carbapenems exhibited similar activities against Bacteroides spp., but SM-7338 was more active than imipenem against Clostridium spp. The MBC of SM-7338 was most commonly the same as or twice the MIC. SM-7338 and imipenem showed excellent activities against bacteria elaborating chromosome- or plasmid-mediated beta-lactamases, including those conferring resistance to broad-spectrum cephalosporins. The activity of SM-7338 was generally unaffected by the culture medium used, pH, 25% human serum, and inoculum size, but the susceptibility of Xanthomonas maltophilia was medium dependent.