Clinical pharmacokinetics of amikacin-teicoplanin in infected severely burned patients: A pilot study

A pilot study of kinetics (concerning both serum and urine), clinical tolerance, and microbiological efficacy of an amikacin (AMK) and teicoplanin (TCN) combination was performed in 6 (35.3 +/- 13.2 years of age, 68.3 +/- 8.6 kg) infected severely burned patients. Mean body surface area affected by 3rd degree burns was 43.0 +/- 23.8 %. Two daily 10 mg/kg (or 683 +/- 76 mg) doses of AMK were infused in 30 min., TCN was infused in 10 min. at the loading dose of 12 mg/kg/12 h during 48 h, then 12 mg/kg/24 h (or 820 +/- 90 mg) at steady state. Two series of blood samples were drawn after the 1st (D1), and respectively the 9th (AMK), and the 7th (TCN) (D5 at steady state) dose. Urine was collected at D1 during the first part of the study. Serum and urinary AMK and TCN levels were measured by FPIA and HPLC respectively. A non-compartmental method was used for kinetics and graphic analysis of both antibiotics. Tolerance to and efficacy of treatment were good. There was no systemic accumulation of antibiotic combination and their kinetics remains linear at steady state. The mean duration of treatment was 8.1 +/- 2.9 and 7.8 +/- 2.7 days respectively for AMK and TCN. There was no statistically significant differences between parameters determined at D1 and D5. Peak AMK concentrations (Cmax) were between 33.5 and 53.0 mg/l. Furthermore, for 5/6 subjects, 10 hours after the beginning of the treatment, serum concentrations were inferior to the assay's Limit of quantification (< 0.6 mg/l). Peak TCN concentrations were relatively high (i.e. 91.9 to 197.5 mg/l), Cmin were somewhat inadequate (i.e. Cmin 12 h (D1) = 9.0 +/- 4.4 mg/l and Cmin 24 h (D5) = 7.6 +/- 3.4 mg/l. A new dosage was calculated on the basis of these experimental results. The aim was to obtain: 1) a Cmax value superior or equal to 50 mg/l and a Cmin of the order of 0.9 mg/l for AMK; 2) a Cmax less than or equal to to 100 mg/l and a Cmin greater than or equal to to 12 mg/l for TCN. Thus, the new regimen was set up as follows: 1) 12 mg/kg of AMK every 12 h (i.e. 1,680 mg per day); 2) 10 mg/kg of TCN every 12 h (i.e. 1,400 mg per day) and suppression of the loading dose. Furthermore, both AMK and TCN were to be infused in 20 minutes. This new regimen was submitted to the Ethics Committee and an assessment will be made on 10 more patients. The revision process described in this preliminary study will optimize treatment for these patients.