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

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. (C) 2003 Elsevier B.V. All rights reserved.