Penetration of antibiotics into human leukocytes and dermal suction blisters

Staphylococcus aureus phagocytized by leukocytes from healthy donors and from patients with chronic granulomatous disease were protected from the antibacterial effect of gentamicin. Considerable numbers of phagocytized bacteria remained viable after exposure for 20 hr to antibiotic concentrations that killed greater than 99% of extracellular bacteria in less than 4 hr. A higher proportion of intracellular bacteria were killed by rifampin; this finding indicated that rifampin penetrates better into the phagocytic vacuole than does gentamicin and/or is more active against phagocytized bacteria than is gentamicin. After oral administration of 450 mg of rifampin to three healthy volunteers, concentrations of the antibiotic in serum and skin blister fluid were measured. Concentrations in serum peaked within 3 hr of oral administration (mean peak level, 13.2 micrograms/ml). Concentrations in blister fluid peaked between 6 hr and 9 hr (mean peak concentration, 2.7 micrograms/ml). Between 9 hr and 12 hr, the concentrations of rifampin in serum and blister fluid were similar; later, levels in blister fluid were higher than those in serum. The mean elimination half-life of rifampin was 2.5 hr in serum and 6.0 hr in blister fluid.