Glycopeptide pharmacokinetics in current paediatric cardiac surgery practice

Abstract

Objective: To examine the evolution of serum concentrations of prophylactic glycopeptides administered during state-of-the-art cardiopulmonary bypass (CPB) and vigorous haemodiafiltration in paediatric patients undergoing cardiac surgery.

Methods: We enrolled infants and children <3 years of age who, based on the preoperative microbiological screening, age and surgical complexity, were at high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Antimicrobial prophylaxis with glycopeptides was administered to 22 patients, randomly assigned to vancomycin (VAN; n=11) versus teicoplanin (TEC; n=11). Fixed doses of each drug (15 mg/kg for VAN and 8 mg/kg for TEC) were administered immediately before the operation, at the time of priming of the extracorporeal circuit, upon admission to the intensive care unit and for 48 h thereafter, q. 8 h for VAN, and once daily for TEC. Vigorous haemodiafiltration was applied during and briefly after CPB.

Results: The second dose of drug added to the prime prevented a fall in serum drug concentrations at the onset of CPB in both groups. A 77% decrease in VAN, versus 53% in TEC concentrations, was observed after the conclusion of CPB. Serum concentrations of TEC>10 microg/ml were observed throughout the treatment period in 91% of patients, while 55% of patients assigned to VAN had serum concentrations consistently >5 microg/ml (p=0.08). Therapeutic serum concentrations were maintained throughout the intraoperative period, particularly with TEC, administered before the first surgical incision, followed by a supplemental bolus in the priming fluid of CPB. Postoperative surgical wound infections occurred in neither group.

Conclusions: The prophylactic use of glycopeptides in paediatric patients at high risk of MRSA infection undergoing cardiac surgery was safe and effective. TEC might be the drug of choice, since stable, therapeutic serum concentrations were easily maintained throughout the treatment period.