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 i n cardiac surgery, three antibiotic prophylactic regimens for patients scheduled to have elective cardiothoracic surgery involving a median sternotomy were evaluated. Design: A prospective, randomized, unblinde d 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.Inte rventions: The patients were selected at random to receive 2 g of cefa mandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of C M 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 = 2 3). Samples from the mammary artery, sternum, and plasma were obtained at various intervals after injection of the antibiotic (10 minutes in travenously) to compare antibiotic levels, assayed for CM concentratio ns, with high-pressure liquid chromatography (HPLC) and plasma bacteri cidal 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 ur inary tract drainage and infusion volume. The mean plasma t1/2 (distri butive or alpha-phase) before bypass was 51.7 +/- 16.7 minutes for gro up 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 m u 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 cont ents 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/m L) 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-organis ms among the three groups, but two patients of groups 1 and 3 with pla sma and tissue CM levels below minimal inhibitor concentration (MIC90) for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp aft er completion of CPB, respectively, developed a pneumonia postoperativ ely caused by Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05). Conclusions: It would be preferable to infuse the ant ibiotic shortly before the operative procedure. However, to keep tissu e and plasma CM values more than MIC90 for common pathogens during the time period studied, a second infusion of 2 g of CM administered afte r onset of CPB suggests better protection against the risk of microbia l infections. Therefore, the findings might be important for the choic e of antibiotic prophylaxis, particularly for high-risk patients. Copy right (C) 1997 by W.B. Saunders Company.