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Minimum inhibitory concentrations (MIC) of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl-a1-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen)), a new semisynthetic cephalosporin derivative were determined by a broth dilution technique. In comparison with cefazolin 130 gram-positive and gram-negative bacteria, recent clinical isolates, were tested. In parallel, inhibition zones for the same organisms were determined by a standardized disc technique using 30-micrograms discs. According to the calculated regression lines a good correlation was found for cefazedone and cefazolin between the MIC values and the diameters of the inhibition zones (correlation coefficients r = --0.90 and --0.92, respectively). Taking into account the dosages recommended for cefazedone and the mean serum concentrations to which they give rise, appropriate categories of sensitivity (break points) for susceptibility testing are recommended.

In two consecutive cross-over studies, each involving 10 healthy volunteers, the pharmacokinetics of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamindo)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) in comparison with cefazolin were investigated after single i.v. and i.m. administration. The doses were: i.v. cefazedone 500 mg and 1000 mg; cefazolin 1000 mg; i.m. cefazedone 500 mg, cefazolin 500 mg. The pharmacokinetic parameters were analysed by applying an open two-compartment model. The pharmacokinetics of cefazedone are nearly identical with those of cefazolin. In particular, it must be noted that cefazedone has a relatively long serum elimination half-life (1.64 +/- 0.23 h after i.v. and 1.85 +/- 0.51 h after i.m. administration) and that cefazedone exhibits, in comparison with cefazolin, a more favourable concentration ratio of central vs. peripheral (= tissue) compartment (1:2).

Distinct bactericidal activity of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) could be demonstrated in 2 Staphylococcus aureus and 3 Escherichia coli strains. The effect was less in 1 strain of Proteus mirabilis. Whereas the activity in serum and bile was higher than in nutrient broth, the bactericidal activity in urine was less pronounced. The combination of cefazedone and gentamicin proved to be bactericidal in low concentrations.

In mice, dogs, and rabbits blood and serum levels were evaluated after parenteral application of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephalothin and cefazolin. In all three animal species cefazedone produced higher and more prolonged serum levels than did cefazolin. Evaluation of serum protein binding in mouse, dog and rabbit serum revealed marked differences between the species. Cefazedone and cefazolin tissue concentrations were evaluated in rabbits. Both antibiotics did not penetrate the CSF or brain tissue. In all other tissues examined (except bone marrow) higher and more prolonged tissue levels were attained with cefazedone than with cefazolin.