Effective serum concentrations of amoxicillin are not always reached in hospitalized patients

OBJECTIVE: The cure of an infection with amoxicillin depends on time above minimal inhibitory concentration (t>MIC). The pharmacodynamic target is t>MIC ≥ 40%. Our aim was to determine what percentage of hospitalized patients treated with intravenous (iv) amoxicilline + clavulanic acid reached this target. METHODS: Serum amoxicillin concentrations were determined in hospitalized patients receiving the standard iv dose of amoxicillin + clavulanic acid: 1000 + 200 mg every 6 hours. Individual pharmacokinetic parameters were calculated using maximum a posteriori Bayesian estimation. t>MIC was calculated using individual pharmacokinetic parameters, dose, dosing interval and MIC. Target attainment at different MIC's (range 0.5-32 mg/L) was determined for standard dose and computer-simulated doses. RESULTS: Serum amoxicillin concentrations were determined in 57 patients (17 female, 40 male) with mean age 67 years (range 23-93 years) and mean creatinine clearance 70 mL/min (range 27-143 mL/min). The mean amoxicillin clearance corrected for body weight was 0.17 L·h -1·kg-1 (range 0.05-0.36 L·h -1·kg-1). Patients older than 70 years had a significantly lower amoxicillin clearance (P = 0.023). 7% and 35% of the patients did not reach the target (t>MIC ≥ 40%) at MIC = 4 mg/L and MIC = 8 mg/L respectively. A computer-simulated dose increase with twice daily 1000 mg amoxicillin decreased these percentages to 0% and 5% respectively. CONCLUSION: The amoxicillin pharmacodynamic target (t>MIC ≥ 40%) is not reached in a substantial part of hospitalized patients treated with the standard iv dose amoxicillin + clavulanic acid. Increasing the amoxicillin dose with twice daily 1000 mg amoxicillin gives maximum target attainment at MIC = 4 mg/L.