Teicoplanin in cardiac surgery: intraoperative pharmacokinetics and concentrations in cardiac and mediastinal tissues

Abstract

The concentrations of teicoplanin in the sera and mediastinal and heart tissues of 23 patients undergoing cardiac surgery were measured after two regimens of teicoplanin administration. Intraoperative pharmacokinetic parameters were also obtained. Patients were randomized into two groups. Those in group 1 were given teicoplanin at 6 mg x kg(-1) intravenously at the time of induction of anesthesia. Patients in group 2 were given teicoplanin at 12 mg x kg(-1) during the same period. The maximum concentration in serum (71 +/- 20 and 131 +/- 44 mg x l(-1)), the minimum concentration in serum (3.6 +/- 1.3 and 6.8 +/- 2.1 mg x l(-1)), the area under the concentration-time curve (AUC) from 0 to 12 h (108 +/- 20 and 217 +/- 38 microg x h x ml(-1)), and the AUC from 0 h to infinity (154 +/- 36 and 292 +/- 77 microg x h x ml(-1)) were twice as high after 12-mg x kg(-1) injections as after 6-mg x kg(-1) injections. No differences in mean residence time (9.7 +/- 4.9 and 8.4 +/- 2.7 h) or terminal half-life (8.5 +/- 3.8 and 7.5 +/- 2.3 h) were observed. Teicoplanin penetrated mediastinal and heart tissues but not sternal bone, where the antibiotic was detectable in only 1 of 13 patients in group 1 and 2 of 10 patients in group 2. In group 1, 7 of 13 patients had teicoplanin concentrations in tissue that were lower than the MIC for 90% of the strains of potential pathogens tested (MIC90) that cause infection after cardiac surgery. All of the patients in group 2 but one had teicoplanin concentrations in tissue (other than in sternal bone) far in excess of the MIC90 for the potential pathogens. In conclusion, the 12-mg x kg(-1) regimen of teicoplanin is followed by a significant increase in teicoplanin concentrations in heart and mediastinal tissues and should be preferred to the 6-mg x kg(-1) regimen if teicoplanin is selected for antimicrobial prophylaxis in open heart surgery.