In vitro studies of the pharmacodynamics of teicoplanin against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium.

摘要

OBJECTIVE: To investigate the basic pharmacodynamic properties of teicoplanin in vitro for Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium. METHODS: The following experiments were performed: (1) bacterial killing by teicoplanin at different concentrations; (2) bacterial killing by teicoplanin at 8 x MIC against the same strains with inocula of 5 x 10(3), 5 x 10(5) and 5 x 10(7) CFU/mL; (3) studies of the postantibiotic effect (PAE) and the postantibiotic sub-MIC effect (PASME) of teicoplanin; (4) studies of the killing by teicoplanin in an in vitro kinetic model following exposure to simulated human serum pharmacokinetic concentrations (6 mg/kg OD at steady state). RESULTS: Concentration-dependent killing was noted against S. epidermidis, with a > 4 log10 difference in CFUs between 2 x MIC and 64 x MIC at 24 h. Also, against S. aureus there was slight concentration-dependent killing, which, however, did not reach 2 log10 CFU/mL. Teicoplanin exerted a similar killing rate at all inocula for S. epidermidis, except for slower initial killing up to 6 h at the highest inoculum. In contrast, overall slower killing at all inocula was seen for S. aureus, where an inoculum effect was noted at the highest inoculum. For E. faecium, only a bacteriostatic effect was noted at all concentrations and inocula. No or very short PAEs were noted for the investigated strains. However, when the strains in the postantibiotic phase were exposed to 0.1, 0.2 and 0.3 x MIC of teicoplanin (PASME), substantial prolongation of the PAEs was seen. Although no significant killing was achieved in our kinetic model for any of the strains, regrowth of S. epidermidis was noted first after 8 h, despite a T > MIC24 of only 5% (1.2 h), illustrating the long post-MIC effect for this strain. For S. aureus, T > MIC was 38%, and regrowth occurred later than for S. epidermidis. Neither killing nor regrowth was seen for E. faecium with a T > MIC24 of 27%. CONCLUSION: Teicoplanin exerted a concentration-dependent bactericidal effect against S. epidermidis, a less notable one against S. aureus, and a bacteriostatic effect against E. faecium. A reduced killing rate with increasing inocula was seen for S. aureus and also for S. epidermidis at the highest inoculum. No or very short PAEs were noted for the investigated strains, but were substantially prolonged with the addition of subinhibitory concentrations. When human pharmacokinetics was simulated (6 mg/kg OD at steady state) in the kinetic model, no net bactericidal effect was noted for any of the strains at 24 h.