Concentration of cefamandole in plasma and tissues of patients undergoing cardiac surgery: The influence of different cefamandole dosage

Objectives: To develop an improved regimen of antibiotic prophylaxis in cardiac surgery, three antibiotic prophylactic regimens for patients scheduled to have elective cardiothoracic surgery involving a median sternotomy were evaluated. Design: A prospective, randomized, unblinded study. Setting: A university teaching hospital. Participants: Sixty-nine men scheduled for elective coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) were included in the study. Interventions: The patients were selected at random to receive 2 g of cefamandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of CM at the beginning of anesthesia followed by an additional dose (2 g) immediately after onset of cardiopulmonary bypass (CPB) (group 2, n = 22), or 4 g of CM just at the initiation of anesthesia (group 3, n = 23). Samples from the mammary artery, sternum, and plasma were obtained at various intervals after injection of the antibiotic (10 minutes intravenously) to compare antibiotic levels, assayed for CM concentrations, with high-pressure liquid chromatography (HPLC) and plasma bactericidal activity as well as infectious complications in these sites as a function of time for the three groups. Measurements and Main Results: There were no significant differences in biometric data, duration of hospitalization, or management of cardiopulmonary bypass, including urinary tract drainage and infusion volume. The mean plasma t1/2 (distributive or alpha-phase) before bypass was 51.7 +/- 16.7 minutes for group 1 and 2 patients and 54.9 +/- 15.9 minutes for group 3 patients. CM plasma values were significantly higher in group 2 (170.3 +/- 105.8 mu g/mL) than in groups 1 and 3 (111.8 +/- 42.2 mu g/mL, 101.2 +/- 57.2 mu g/mL) at the end of bypass periods (p < 0.05). The antibiotic contents of mammary artery and sternum samples of group 2 (15.6 +/- 4.7 mu g/mL, 9.5 +/- 4.7 mu g/mL) were significantly higher after completion of CPB compared with group 1 (5.7 +/- 1.9 mu g/mL, 3.8 +/- 2.9 mu g/mL) and group 3 (6.3 +/- 3.5 mu g/mL, 3.6 +/- 1.8 mu g/mL) (p < 0.05). There were no significant differences in distribution of micro-organisms among the three groups, but two patients of groups 1 and 3 with plasma and tissue CM levels below minimal inhibitor concentration (MIC90) for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp after completion of CPB, respectively, developed a pneumonia postoperatively caused by Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05). Conclusions: It would be preferable to infuse the antibiotic shortly before the operative procedure. However, to keep tissue and plasma CM values more than MIC90 for common pathogens during the time period studied, a second infusion of 2 g of CM administered after onset of CPB suggests better protection against the risk of microbial infections. Therefore, the findings might be important for the choice of antibiotic prophylaxis, particularly for high-risk patients. Copyright (C) 1997 by W.B. Saunders Company.