A pilot study to determine the feasibility of continuous cefazolin infusion.
BACKGROUND: Animal studies have shown that continuous infusion of beta-lactam antibiotics is more effective than intermittent dosing. We studied several dosing regimens of cefazolin in humans to determine safety and whether or not adequate serum and tissue antibiotic concentrations could be achieved in patients undergoing cardiac bypass. METHODS: A prospective, randomized pilot study was conducted at a university-affiliated teaching hospital over a 2-year period in patients undergoing first-time coronary artery bypass grafting. One hundred and thirty-seven patients were randomized to one of three groups. Group 1 (n = 64) received 1 g of cefazolin intravenously before operation and 1 g intravenously at the end of cardiopulmonary bypass. Group 2 (n = 35) received 2 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 20 mg/min throughout surgery. Group 3 (n = 38) received 3 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 15 mg/min throughout surgery. Venous blood and subcutaneous fat samples were obtained from the sternal wound in a subset of 34 patients at incision, 0.25 h, 0.5 h, and 1 h; at the end of cardiopulmonary bypass; and at wound closure. Venous blood was sampled in the recovery room and on postoperative day 1. Cefazolin concentrations in the samples were determined by reverse-phase high-performance liquid chromatography using a C18 column. RESULTS: Serum cefazolin concentrations were higher for group 3 when compared with group 1 at all six intraoperative intervals (p < 0.02) and for group 2 when compared with group 1 at four of six intraoperative intervals (p < 0.04). When compared with group 1, tissue cefazolin concentrations were higher for group 3 at all intraoperative intervals (p < 0.02). No related toxicity or adverse events were observed. CONCLUSION: Cefazolin administered as a large preoperative bolus with continuous intraoperative infusion resulted in higher serum and tissue concentrations when compared with conventional intermittent dosing. Pharmacodynamically, continuous infusion of beta-lactam antibiotics may be superior to intermittent dosing when used for perioperative prophylaxis against wound infection, especially for cases in which the antibiotic is not redosed intraoperatively.
Waltrip, T; Lewis, R; Young, V; Farmer, M; Clayton, S; Myers, S; Gray, LA; Galandiuk, S
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