In vitro activity and beta-lactamase stability of a new carbapenem, SM-7338

Abstract

SM-7338, a new carbapenem, inhibited most members of the family Enterobacteriaceae at MICs of 0.015 to 0.25 .mu.g/ml, including Klebsiella oxytoca, Citrobacter freundii, Enterobacter cloacae, and Proteus vulgaris isolates resistant to cefotaxime, ceftazidime, piperacillin, and gentamicin. It was two- to eightfold more active than imipenem, but it inhibited Pseudomonas aeruginosa at 1 to 8 .mu.g/ml, which was comparable to the activity of imipenem. Haemophilus, Neisseria, and Branhamella species were inhibited by .ltoreq. 0.25 .mu.g/ml, which was superior to the activity of imipenem. SM-7338 inhibited Staphylococcus aureus and coagulase-negative staphylococci at 0.25 .mu.g/ml, but for methicillin-resistant isolates MICs were 4 to 16 .mu.g/ml. Group A, B and C. streptococci and Streptococcus pneumoniae were inhibited by .ltoreq. 0.03 .mu.g/ml. Bacteriodes species, including clindamycin-resistant isolates, were inhibited by 0.25 .mu.g/ml. There was no major inoculum size effect, and the MBCs were within a dilution of the MICs. SM-7338 was more active than imipenem at an acid pH under anaerobic conditions. Plasmid .beta.-lactamases of TEM-1, TEM-2, TEM-3, TEM-5, SHV-1, SHV-2, PSE-1, PSE-2, PSE-3, OXA-2, OXA-3, OXA-4, OXA-5 and OXA-7; Staphylococcus aureus enzymes; and the chromosomal .beta.-lactamases P-99 and K-1; Morganella species; and Proteus vulgaris did not hydrolyze SM-7338. The repeated transfer of organisms increased the MICs of SM-7338, as it did the MICs of imipenem.