TEICOPLANIN IN CARDIAC-SURGERY - INTRAOPERATIVE PHARMACOKINETICS AND CONCENTRATIONS IN CARDIAC AND MEDIASTINAL TISSUES

The concentrations of teicoplanin in the sera and mediastinal and hear t tissues of 23 patients undergoing cardiac surgery were measured afte r two regimens of teicoplanin administration, Intraoperative pharmacok inetic parameters were also obtained, Patients were randomized into tw o groups, Those in group 1 were given teicoplanin at 6 mg kg(-1) intra venously at the time of induction of anesthesia, Patients in group 2 w ere given teicoplanin at 12 mg kg(-1) during the same period. The maxi mum concentration in serum (71 +/- 20 and 131 +/- 44 mg 1(-1)), the mi nimum concentration in serum (3.6 +/- 1.3 and 6.8 +/- 2.1 mg 1(-1)), t he area under the concentration-time curve (AUG) from 0 to 12 h (108 /- 20 and 217 +/- 38 mu g h ml(-1)), and the AUC from 0 h to infinity (154 +/- 36 and 292 +/- 77 mu g h ml(-1)) were twice as high after 12- mg kg(-1) injections as after 6-mg kg(-1) injections. No differences i n 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 penet rated mediastinal and heart tissues but not sternal bone, where the an tibiotic was detectable in only 1 of 13 patients in group 1 and 2 of 1 0 patients in group 2. In group 1, 7 of 13 patients had teicoplanin co ncentrations in tissue that were lower than the MIC for 90% of the str ains of potential pathogens tested (MIC90) that cause infection after cardiac surgery. All of the patients in group 2 but one had teicoplani n concentrations in tissue (other than in sternal bone) far in excess of the MIC90 for the potential pathogens, In conclusion, the 12-mg kg( -1) regimen of teicoplanin is followed by a significant increase in te icoplanin concentrations in heart and mediastinal tissues and should b e preferred to the 6-mg kg(-1) regimen if teicoplanin is selected for antimicrobial prophylaxis in open heart surgery.