Affiliation:
1. Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan
Abstract
SCE-963 {7β-[2-(2-aminothiazol-4-yl)acetamido]-3-[({1-(2-dimethylaminoethyl)- 1H-tetrazol-5-yl}thio)methyl]-ceph-3-em-4-carboxylic acid}, a new semisynthetic cephalosporin, showed excellent antibacterial activity against gram-positive and gram-negative bacteria, including
Haemophilus influenzae
, indole-positive
Proteus, Enterobacter
species, and
Citrobacter freundii
. The minimum inhibitory concentrations of SCE-963 against most strains of clinically isolated
Escherichia coli, Klebsiella pneumoniae, H. influenzae
, and
Proteus mirabilis
were within the range of 0.2 to 0.78 μg/ml. These activities were about 10 times more potent than those of cefazolin, cephaloridine, and cephalothin. Variations in pH, addition of horse serum, and type of growth medium had no significant effect on the activity of the cephalosporin, but the inoculum size elicited a considerable effect on the activity of β-lactamase-producing strains of bacteria. SCE-963 exerted bactericidal and bacteriolytic effects on
Staphylococcus aureus
and
E. coli
. The pronounced in vitro activity was reflected in the remarkable protection in mice infected with a wide range of gram-negative bacteria, such as
E. coli, K. pneumoniae, P. mirabilis, Proteus vulgaris, Proteus morganii
, and
Proteus rettgeri
. The protective effects of SCE-963 in mice infected with
E. coli, K. pneumoniae
, and
P. vulgaris
varied according to the challenge dose. The activity of SCE-963 was far more potent when the drug was administered parenterally rather than orally.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology