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Eur J Cardiothorac Surg 2004;25:256-260
© 2004 Elsevier Science NL

Pharmacokinetics of intravenous flucloxacillin and amoxicillin in neonatal and infant cardiopulmonary bypass surgery

^a Department of Cardiac Surgery, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
^b Department of Microbiology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
^c Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, Bristol, UK

Received 1 August 2003; received in revised form 12 November 2003; accepted 16 November 2003.

^* Corresponding author. Tel.: +44-121-333-9437; fax: +44-121-333-9441
e-mail: david.barron{at}bhamchildrens.wmids.nhs.uk

Objective: To determine the blood and tissue concentrations of flucloxacillin and amoxicillin during cardiopulmonary bypass (CPB) in infants weighing less than 5 kg. Methods: Eleven patients aged between 3 and 60 days and weighing <5 kg. Intravenous flucloxacillin 30 mg kg^-1 and amoxicillin 30 mg kg^-1 were administered at time of anaesthesia. Blood and muscle samples were collected at four stages of the operation: immediately before commencement of CPB; before cross-clamping; after weaning of CPB; and at the time of skin closure. Concentrations, half-lives (t_1/2), clearance and volume of distribution were calculated for both antibiotics in serum and tissue. Results: After connection to CPB the mean serum concentration of flucloxacillin decreased by 42.5% from 75.5 to 43.4 mg l^-1 (P=0.003) and that of amoxicillin decreased by 36.2% from 73.3 to 46.7 mg l^-1 (P=0.021). Serum concentrations of the two antibiotics decreased by a further 16.5 and 14.5% during the remainder of the surgery, but remained >15-fold above the expected minimum inhibitory concentration (MIC) for target pathogens. Muscle concentrations of both antibiotics reached MIC values by the time of the first sample and there was no decrease associated with connection to CPB. Levels remained >8-fold above MIC for target pathogens throughout the procedure. The t_1/2 for flucloxacillin was 2.64(±0.23) h and for amoxicillin was 3.16(±0.29) h, both of which are more than double the values in normal adults. There was an equivalent reduction in clearance for both antibiotics. Conclusions: Single doses of flucloxacillin and amoxicillin at 30 mg kg^-1 maintain serum and muscle concentrations well above the MIC throughout cardiac surgery. This is partly due to a prolonged t_1/2 and reduced clearance of both antibiotics in infants.

Key Words: Antibiotics • Cardiopulmonary bypass • Neonates

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