TABLE 3.

Bacterial tissue burdens in rabbits infected with strain B2.0 and untreated or treated with two different doses of daptomycin in an aortic valve endocarditis modela

GroupbBacterial tissue burden (log10 CFU/g) (mean ± SD) in:
Endocardial vegetationsSpleensKidneys
No DAP (n = 5)7.3 ± 1.05.4 ± 0.25.1 ± 0.6
DAP-12 (n = 9)c6.3 ± 1.83.2 ± 1.6e2.1 ± 1.9e
DAP-18 (n = 9)d4.4 ± 1.6e,f2.3 ± 1.6e2.5 ± 1.2e
  • a A daptomycin dose of 12 mg/kg in rabbits produced an AUC of 719 μg · h/ml, comparable to the human 6-mg/kg dose (which produced an AUC of 632 μg · h/ml). A daptomycin dose of 18 mg/kg in rabbits produced an AUC of 965 μg · h/ml, comparable to the human 10-mg/kg dose (which produced an AUC of 1,039 μg · h/ml).

  • b The three groups were untreated control rabbits (no daptomycin [No DAP]) and rabbits treated with 12 mg of daptomycin/kg/day for 4 days (DAP-12) or 18 mg of daptomycin/kg/day for 4 days (DAP-18).

  • c Eleven rabbits were allocated to this arm. Two rabbits, one found dead on day 1 and the other on day 2, received one dose of daptomycin each and were not included in the data analysis. Two euthanized rabbits were included in the analysis: one, given two doses of daptomycin, was found moribund on day 2 (endocardial vegetation titer of 6.48 log10 CFU/g); the other, given three doses of daptomycin, was found moribund on day 4 (vegetation titer of 8.28 log10 CFU/g).

  • d Nine rabbits were allocated to this arm. One rabbit given two doses of daptomycin was found moribund and euthanized on day 2 (endocardial vegetation titer of 2.79 log10 CFU/g) and included in the data analysis.

  • e Significantly different from the value obtained for the no-DAP group (P < 0.05).

  • f Significantly different from the value obtained for the DAP-12 group (P < 0.05).