Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations

Background: Postoperative infections remain common after high-risk gastroin testinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Wor cester, Mass), derived from yeast cell walls, promotes phagocytosis and int racellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antib iotics to reduce mortality in rat peritonitis. Hypothesis: We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing a gent. Design: Multicenter, prospective, randomized, double-blind, placebo-control led trial of 1249 patients prospectively stratified into colorectal or nonc olorectal strata. Setting: Thirty-nine medical centers throughout the United States. Patients: Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors. Interventions: PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preopera tively and 3 times postoperatively. All patients received standardized anti biotic prophylaxis. Main Outcome Measures: Serious infection or death within 30 days. Results: All randomized patients revealed no difference in serious infectio ns and deaths in the treated groups compared with placebo groups (15% vs 14 %, P>.90). In the prospectively defined noncolorectal stratum (n=391), PGG- glucan administration was associated with a statistically significant relat ive reduction (39%) in serious infections and death (placebo, 46 [36%] of 1 29 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P<.02). PGG-glucan reduced postoperative infection or death in malnourished patien ts having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan gr oup; P<.001). Study drug was stopped owing to adverse effects more frequent ly for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the p lacebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, r espectively, P<.003). Conclusion: Perioperative administration of PGG-glucan reduced serious post operative infections or death by 39% after high-risk noncolorectal operatio ns.