The in vitro and in vivo antibacterial activities of
carumonam (AMA-1080), a synthetic
sulfazecin derivative, were compared with those of
aztreonam,
cefoperazone,
ceftazidime, and
cefsulodin.
Carumonam was highly active in vitro against members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae and weakly active against Streptococcus pneumoniae, but it was not active against Staphylococcus aureus. The MICs of
carumonam for 90% of 1,156 clinical Enterobacteriaceae isolates were between 0.013 and 25 micrograms/ml, which were the lowest MICs of the
antibiotics tested. The MIC of
carumonam for 90% of Klebsiella oxytoca was 0.2 micrograms/ml, whereas that of
aztreonam was 50 micrograms/ml. The superiority of
carumonam to
aztreonam and the reference
cephalosporins was also demonstrated by their activities against Klebsiella pneumoniae and Enterobacter cloacae. The MIC of
carumonam for 90% of P. aeruginosa was 12.5 micrograms/ml, which was comparable to the MICs of
aztreonam and
ceftazidime.
Carumonam showed a high affinity for the
penicillin-binding protein 3 of gram-negative bacteria, but not for the
penicillin-binding proteins of S. aureus and Bacteroides fragilis.
Carumonam was resistant to hydrolysis by 12 plasmid-mediated
beta-lactamases and 7 chromosomal
beta-lactamases. It was more stable than
aztreonam to hydrolysis by the
beta-lactamase of K. oxytoca; this stability is related to the superiority of the in vitro and in vivo activities of
carumonam to those of
aztreonam against this species. In general, the protective activities (50% effective dose) of
carumonam and reference
antibiotics in mice with experimental intraperitoneal
infections correlated with the in vitro activities (MIC);
carumonam showed excellent protective activity against most aerobic gram-negative bacteria.