cefuzonam and Escherichia-coli-Infections

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

Concentrations of cefuzoname in cerebrospinal fluid (CSF) were determined in a total of 16 rabbits, 5 with healthy meninges, 5 with Staphylococcus aureus meningitis, and 6 with Escherichia coli meningitis. Mean percentages of the maximum concentration of the drug in CSF versus that in serum were 0.57, 3.37, and 4.40% for healthy rabbits, those with staphylococcal meningitis, and those with E. coli meningitis, respectively. The percentages of the area under the concentration-time curve of cefuzoname in CSF versus that in serum were, in the order of healthy group, staphylococcal meningitis group, and E. coli meningitis group, 0.61, 4.99, and 8.04% at 15 to 60 min, 1.44, 7.09, and 12.7% at 15 to 120 min, and 1.87, 8.07, and 15.8% at 15 to 180 min after administration, showing significant differences between the healthy and meningitis groups. All of the values in the E. coli meningitis group were greater than those of the staphylococcal meningitis group, but the differences were not significant. The ratios of the half-life of cefuzoname in CSF to that in serum were 2.10, 1.98, and 3.37 for the healthy, staphylococcal meningitis, and E. coli meningitis groups, respectively, with no significant difference between the three groups. Cefuzoname seems to be among the middle ranks of beta-lactam agents as far as penetration rate is concerned; however, when its potent antibacterial activity and broad spectrum are taken into account, the concentrations in CSF in patients with meningitis seem worth examining.

Topics: Animals; Ceftizoxime; Cephalosporins; Escherichia coli Infections; Half-Life; Meningitis; Rabbits; Staphylococcal Infections