Penetration of Antibiotics into Fibrin Loci in Vivo. III. Intermittent vs. Continuous Infusion and the Effect of Probenecid

In a rabbit model previously used for single-dose studies, penicillins or cephalosporins were given as repeated iv boluses or by continuous infusion. With both methods of administration, levels of antibiotic in sc fibrin clots rose progressively until they were similar to peak concentrations of free drug in serum. Levels of ampicillin in these fibrin loci were strikingly higher when the drug was injected intermittently than when the same total dose was given by continuous infusion. This appeared to be due to the higher peak levels attained in serum with the intermittent approach. The concomitant administration of probenecid increased the-levels of ampicillin or oxacillin in serum and fibrin clots but did not affect distribution between the two compartments.