hr-810 and Granuloma

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Topics: Abscess; Animals; Bacterial Infections; Cefotaxime; Cefpirome; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Granuloma; Imipenem; Male; Mice; Mice, Hairless; Mice, Inbred C3H; Pneumonia; Rats; Rats, Inbred Strains; Sepsis; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections

Therapeutic effects of intravenously administered cefpirome on experimental bacterial infections in croton oil-induced rat granuloma pouches were compared with those of ceftazidime, moxalactam, cefoperazone, and cefotaxime. Its pharmacokinetic profile in pouch exudate was also examined. Cefpirome showed bactericidal effects and long-lasting bacterial growth-inhibitory effects in granuloma pouches infected in Escherichia coli Ec-7, and its effects were almost equal to those of the other antibiotics. Against Pseudomonas aeruginosa TM-11 infection, cefpirome was more active than moxalactam, cefoperazone, and cefotaxime and comparable to ceftazidime. Cefpirome had the strongest activity against Staphylococcus aureus Smith infection among the five antibiotics, showing bactericidal effects and long-lasting bacterial growth-inhibitory effects. The level of cefpirome in pouch exudate peaked at 1 h after administration, with a value of 16.4 micrograms/ml, and declined in a pattern similar to that of ceftazidime. When compared in peak level, the exudate level of cefpirome was 1.8 to 2.6 times higher than the values of moxalactam, cefoperazone, and cefotaxime. The in vitro exudate protein binding of cefpirome was 8.8%, which was the lowest among the antibiotics used.

Topics: Animals; Bacterial Infections; Cefpirome; Cephalosporins; Croton Oil; Exudates and Transudates; Granuloma; Male; Microbial Sensitivity Tests; Protein Binding; Rats; Rats, Inbred Strains