cp-70429 and cefuzonam

The in vitro and in vivo antibacterial activities of sulopenem (CP-70,429),a new parenteral penem antibiotic, were compared with those of imipenem (IPM), flomoxef, cefuzonam (CZON) and cefotaxime. Sulopenem possessed broad-spectrum activities against Gram-positive bacteria and Gram-negative bacteria. Antibacterial activities of sulopenem against methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae were equivalent to or somewhat superior to those of IPM. Against members of the family Enterobacteriaceae, sulopenem was 4- to 260-fold more active than reference antibiotics with broad-spectra. In a killing kinetics study for Haemophilus influenzae, sulopenem showed a 99.9% decrease of viable cells after 8 hours at a concentration of 0.20 micrograms/ml. This effect was obtained at a concentration 8-fold lower than that of IPM. The protective effects of sulopenem in murine experimental systemic infections were superior to those of imipenem/cilastatin. In murine experimental mixed infection with Escherichia coli and Bacteroides fragilis, sulopenem had lower ED50, in other words stronger antimicrobial activities than IPM. The therapeutic effect of sulopenem are related well with its MIC value. In guinea pigs experimental lung infection with Klebsiella pneumoniae, sulopenem was more effective than CZON or cefotiam.

Topics: Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; beta-Lactam Resistance; Cefotaxime; Ceftizoxime; Cephalosporins; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Guinea Pigs; Imipenem; Klebsiella Infections; Lactams; Lung Diseases; Mice; Mice, Inbred ICR; Thienamycins

In vitro activities of sulopenem, a novel parenteral penem, was compared with those of imipenem, flomoxef, cefuzonam, cefoperazone and sulbactam/ampicillin against 66 reference strains (19 genera, 61 species) and 392 recent clinical isolates of anaerobic bacteria and fastidious aerobic bacteria. Sulopenem had a very broad spectrum against anaerobic bacteria. In general, this compound was active against anaerobic reference strains with MICs of < or = 0.78 micrograms/ml, while being the least active against Bifidobacterium spp. and less active than imipenem against Lactobacillus spp. Sulopenem was more active against Bacteroides fragilis isolates than imipenem and had the highest activities against Bacteroides thetaiotaomicron, Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp. and Peptostreptococcus spp. among the antibiotics tested. Sulopenem was not hydrolyzed by oxyiminocephalosporinase type 1 produced by B. fragilis GAI-0558, GAI-7955 and GAI-10150 and its stability was comparable to imipenem. Its susceptibilities to hydrolysis by a metallo-beta-lactamase from B. fragilis GAI-30144 was less than imipenem. Sulopenem (120 mg/kg, 3 times a day for 4 days) was as effective as imipenem/cilastatin against a mixed intraabdominal mice infection due to E. coli and B. fragilis. Sulopenem (20 mg/kg twice a day for 5 days) did not induce an overgrowth of Clostridium difficile in the caecum of mice.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacteria, Anaerobic; beta-Lactamases; beta-Lactams; Cecum; Cefoperazone; Ceftizoxime; Cephalosporins; Clostridioides difficile; Drug Stability; Drug Therapy, Combination; Imipenem; Lactams; Male; Mice; Mice, Inbred ICR; Sulbactam; Thienamycins