To assess the efficacy of single-dose antibiotic prophylaxis in coronary artery bypass grafting, 1,016 consecutive patients were prospectively randomized to receive either a single dose or a three-day course of cefuroxime. Nine patients (0.9%) died within seven days; no death was caused by infection. For various reasons 163 other patients were not evaluable. Therefore, 844 patients were evaluated. Patients in group A (n = 419) received 20 mg/kg cefuroxime intravenously at induction of anaesthesia; group B (n = 425) received the same dose followed by 750 mg t.i.d. for three consecutive days. Both groups were comparable regarding all risk factors. The efficacy of the prophylactic regimens was evaluated by comparison of occurrence of wound infection in both groups. No significant differences in wound infection were observed between the two treatment groups: sternal site infection in the single-dose prophylaxis group was 14% versus 13% in the three-day course group; donor site infection occurred in 38% versus 39%. It is concluded that in coronary artery bypass grafting a single dose of cefuroxime is as effective as a three-day course in the prevention of wound infection.

The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to O.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against the stable unencapsulated mutant E. coli 07:K-, showed reduction but not lack of the capsular polysaccharide of encapsulated E. coli 07:K1, and better exposure of subcapsular epitopes, after incubation with 0.5 x the MICs of antibiotics. Flow cytometric analysis of encapsulated E. coli exposed to netilmicin, ciprofloxacin, and fleroxacin revealed that the reduction in capsular material was homogeneous among the bacterial population. Treatment with cefepime and ceftriaxone induced two populations of bacteria that differed in the amount of K antigen present. These results indicate that sub-MICs of netilmicin, ceftriaxone, fleroxacin, and ciprofloxacin influenced complement-mediated opsonization, probably due to changes in the capsular polysaccharide structure.The outer structures of bacteria play an important role in the interaction between bacteria and host defenses during infections. Encapsulated strains of Escherichia coli have been shown to be resistant to the lytic and opsonic activities of serum (6, 7) and to phagocytosis by human polymorphonuclear leukocytes (PMN) (8). The invasive capacity of these bacteria is correlated to their ability to resist killing by normal human serum (9,14). Especially Kl capsule appears to be responsible for serum resistance of strains that are otherwise exquisitely sensitive to the action of serum (2) and that are easily ingested and degraded by PMN (21). However, during infection bacteria are exposed not only to the defense mechanisms of the host but also to the action of antimicrobial agents. It is well known that antibiotics exert part of their action in the body fluids, at concentrations below the MICs. Sub-MICs of certain antibiotics have been shown to modify the morphological and ultrastructural characteristics of bacteria, influencing the interactions with host defense mechanisms, i.e., opsonophagocytosis (5, 15). In previous studies we reported that preexposure of encapsulated E. coli strains to sub-MICs of an aminoglycoside (netilmicin) and of a cephalosporin (ceftriaxone) enhanced the phag...

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