Effects of rate of infusion and probenecid on serum levels, renal excretion, and tolerance of intravenous doses of cefoxitin in humans: comparison with cephalothin.
Using a randomized crossover design, 1-g intravenous doses of cephalothin and cefoxitin, a cephalosporinase-resistant cephamycin, were infused into 12 normal adult males over periods of 120, 30, and 3 min, the last with and without prior intravenous infusions of probenecid (1 g). Mean peak serum concentrations of antibiotic activity after cephalothin infusions were 23, 56, 103, and 102 mug/ml, respectively, and after cefoxitin infusions they were 27, 74, 115, and 125 mug/ml, respectively. Probenecid treatment prolonged the terminal serum half-life of cephalothin-like activity from 0.52 to 1.0 h, and of cefoxitin from 0.68 to 1.4 h. In contrast to cephalothin, which was found to be metabolized about 25% to the less active desacetyl form, cefoxitin was metabolized less than 2% to the virtually inactive descarbamyl form, as judged from urinary recoveries. Neither antibiotic displayed detectable organ toxicity. Of 300 recent clinical isolates of gram-negative bacilli other than Pseudomonas spp., 83% were susceptible to cephalothin but 95% were susceptible to cefoxitin. Organisms resistant to cephalothin but susceptible to cefoxitin included strains of Escherichia coli, Proteus vulgaris, Klebsiella spp., Serratia marcescens, Enterobacter spp., and Bacteroides spp.
Goodwin
C S
CS
Raftery
E B
EB
Goldberg
A D
AD
Skeggs
H
H
Till
A E
AE
Martin
C M
CM
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002440:Cefoxitin / Q000493:pharmacokinetics* / Q000494:pharmacology; D002512:Cephalothin / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008826:Microbial Sensitivity Tests; D011339:Probenecid / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D002440:Cefoxitin; D011339:Probenecid; D002512:Cephalothin