cefotaxime 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

The rat granuloma pouch model was used to study the penetration of imipenem into inflammatory exudate and its efficacy in an experimental local infection. Rats were given a single intravenous injection of drug via the tail vein at a dose of 40 mg/kg. The peak concentrations of imipenem, ceftizoxime, cefazolin, and cefsulodin in exudates ranged from 10.1 to 12.3 mg/l, except that ampicillin achieved only 5.4 mg/l. Imipenem rapidly reached peak concentration after injection, but the half life for elimination of imipenem from exudate was 77.7 min, which was shorter than that of other beta-lactam antibiotics. Imipenem exhibited more rapid reduction in bacterial growth than cefsulodin in an experimental local infection with Pseudomonas aeruginosa in the pouch model. The results suggested that imipenem was an effective agent in treating the local infection.

Topics: Animals; Anti-Bacterial Agents; Cefazolin; Cefotaxime; Cefsulodin; Ceftizoxime; Exudates and Transudates; Granuloma; Imipenem; Inflammation; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Inbred Strains; Thienamycins

Cefodizime was compared with cefotaxime (CTX) in regard to its distribution to an inflammatory site (exudate in croton oil-induced granuloma pouch) of rats and its therapeutic effects on experimental infections in such pouches after intravenous injection. Cefodizime levels in rat serum and pouch exudate were higher than those of CTX, and the former compound disappeared from the serum and pouch exudate far more slowly than the latter. In the tests for therapeutic effects, cefodizime showed almost the same degree of inhibitory activity as CTX against growth in pouch exudate of Escherichia coli Ec-7, Proteus mirabilis Pm-428, and Serratia marcescens Sm-390 for which the minimum inhibitory concentrations (MICs) of cefodizime were equal to or greater than the CTX values, and such activity of cefodizime lasted for a longer period than that of CTX. These results suggest that the above pharmacokinetic features of cefodizime compensate for its MICs against organisms displaying lower values for CTX.

Topics: Animals; Bacterial Infections; Cefotaxime; Croton Oil; Exudates and Transudates; Granuloma; Male; Microbial Sensitivity Tests; Rats