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Bactericidal Activity and Pharmacology of Cefazolin

The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against Escherichia coli and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 μg/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.