Table 1

Pharmacokinetic-pharmacodynamic (PK/PD) parameters of therapeutic groups and bacterial counts from TCF at the beginning of treatment (day 1)a

Therapeutic group (n)Bacterial countbSerumTCFEquivalent value for humans
Cmax (mg/liter)AUC0-24h (mg/h/liter)Cmax (mg/liter)Trough (mg/liter)AUC0-24h (mg/h/liter)T>MIC (%)
FOS, 500 mg/kg/12 h (n = 18)6.60 ± 1.042636201128.8808ND8 g/day
D100, 100 mg/kg/day (n = 26)6.40 ± 0.94140120040181100ND10 mg/kg/day
D45, 45 mg/kg/day (n = 26)6.35 ± 0.921037952610830ND6 mg/kg/day
RIF, 25 mg/kg/12 h (n = 23)6.19 ± 0.86242776.63.8304ND900 mg/day
IMI, 120 mg/kg/12 h (n = 15)7.08 ± 0.8081ND321.1ND1002 g/day
FOS+D100 (n = 20)6.50 ± 0.92
FOS+D45 (n = 20)6.45 ± 0.74
FOS+RIF (n = 19)6.78 ± 0.90
FOS+IMI (n = 30)7.00 ± 0.98
D100+RIF (n = 25)6.13 ± 0.66
CON (n = 20)6.66 ± 1.04
  • a Abbreviations: Cmax, peak concentration; AUC0-24h, the area under the concentration-time curve over 24 h; T>MIC, the time the drug concentration remained above the MIC; ND, not determined. Abbreviations for therapeutic groups are defined in the Fig. 2 legend. All of the methodology used for PK/PD studies has been described elsewhere (16). On the basis of previous reports (17, 18), we used the dose of antibiotic that achieved PD parameters in the TCF close to those in human serum; we adjusted the AUC/MIC ratios for all drugs except IMI, for which we selected a dose previously used in rats that mimics the usual dosage in humans due to difficulties in optimizing the PD parameters against the MRSA strain (19).

  • b Mean log CFU/ml ± standard deviation from TCF at day 1.