Bactericidal activity and killing rate of serum in volunteers receiving teicoplanin alone or in combination with oral or intravenous rifampin

Abstract

A total of 10 volunteers, in two groups of 5 each, received the following on separate days: group 1,200 mg of teicoplanin intravenously (i.v.), 600 mg of rifampin orally, or teicoplanin-rifampin; group 2,400 mg of teicoplanin i.v., 300 mg of rifampin i.v. in 60 min, or teicoplanin-rifampin. Blood samples were obtained before, at the end, and at 1 and 6 h after the administration of the antibiotics. Bactericidal activity in serum (SBA) was measured in microtiter plates against 20 clinical isolates (five strains each) of oxacillin-susceptible and-resistant Staphylococcus aureus and Staphylococcus epidermidis. The endpoint of the SBA corresponded to 99.9% killing. Killing rates were measured in serum obtained at 1 and 6 h. The concentrations of each antibiotic were measured by bioassay. The antibiotic concentrations in serum obtained at the peak and at 1 and 6 h after the end of administration were as follows: group 1, teicoplanin, 26, 15.6, and 8.4 mg/liter; rifampin, not determined, 8.3, and 3.8 mg/liter; group 2, teicoplanin, 66, 29.4, and 11.5 mg/liter; rifampin, 14.8, 3.8, and 1.2 mg/liter. Higher median SBAs were obtained after treatment with rifampin than after that with teicoplanin. No interaction was observed between rifampin and teicoplanin. This was confirmed by determination of the killing rate in serum. Teicoplanin killed more slowly than rifampin. The combination had the same killing rate as rifampin alone. Rifampin neither improved nor antagonized the bactericidal activity of teicoplanin, as determined by the SBAs or the rate of killing.