ABSTRACT
The purpose of this study was to investigate the pharmacokinetics of teicoplanin (TEIC) in patients undergoing open heart surgery. We also attemped to define the optimum TEIC therapy protocol for prevention of perioperative infection and for treatment of staphylococcal endocarditis such as that caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Serum TEIC concentrations were measured in 14 patients divided into two groups of 7 patients each undergoing elective open heart surgery. Patients in group I received 400mg of TEIC and patients in group II received 800mg, both administered as a slow intravenous infusion over 20min immediately after induction of anesthesia. The peak serum level (mean±standard error) of TEIC was respectively 57±11 and 139±39μg/ml at 2min after administration and then the TEIC level decreased gradually to 26± 7 and 55±10μg/ml at 60min after administration. The serum level of TEIC decreased rapidly to 17±5 and 31±7μg/ml, respectively, at the start of extracorporeal circulation (ECC), and was 11±2 and 27±6μg/ml after 60min of ECC, 8±2 and 23±7μg/ml at 2min after the termination of ECC, 8±3 and 23±6μg/ml at 60min after the termination of ECC, and 7±2 and 22±5μg/ml on admission to ICU. No side effects were seen during the study, such as red neck syndrome, renal dysfunction, hearing disorders, or postoperative infection. Our results suggested that the optimum dose of TEIC for prevention of perioperative infection was around 400mg, providing levels in excess of the MIC for most pathogens that have been found to cause infection following open heart surgery, including MRSA. In addition, a dose of 800mg was needed to keep trough levels above 20μg/ml for treatment of staphylococcal endocarditis. It was also suggested that half of the initial dose should be administered on admission to ICU and also at the start of ECC if the operation is going to last longer than 7h on the basis of the concentration-time curve.
ABSTRACT
Recently several papers have been published on the use of vancomycin (VCM) to prevent perioperative infection during open-heart surgery, but there have been few papers from Japan. In this study, we evaluated the pharmacokinetics of VCM in the serum and right atrial tissues of eight patients (4 men and 4 women) who underwent open-heart surgery, to prevent perioperative infection. Preoperatively all patients had neither hearing disorder nor renal dysfunction. A total of 1, 000mg of VCM was given intravenously over 40-50 minutes before a skin incision. The serum levels of VCM were measured every 20 minutes during open-heart surgery with enzyme-immunoassay. VCM levels in the right atrial tissues were also assayed before the start of extracorporeal circulation (ECC). The peak serum levels of VCM were 55.3±10.1μg/ml and decreased gradually to 10μg/ml prior to the ECC. During the ECC, the serum levels of VCM remained between 7.6 and 9.9μg/ml, while VCM levels in the right atrial tissues were 18.9±6.9μg/ml (serum/tissue ratio: 0.34). Staphylococcal infection is generally inhibited by VCM levels of 2.0-6.5μg/ml. This study suggests that 1, 000mg of VCM given intravenously before a skin incision may be effective to prevent perioperative infection during open-heart surgery.