Increasing antibiotic dose decreases polymicrobial infection after hemorrhagic shock

: Hemorrhagic shock has been shown to increase the susceptibility to infection despite the administration of conventionally accepted doses of antimicrobial drugs. The efficacy of increasing antibiotic dose in a model of mixed gram-negative infection, both with and without hemorrhagic shock, was examined. Shock was induced by bleeding rats to a mean arterial pressure of 45 millimeters of mercury for 45 minutes followed by resuscitation with shed blood and saline solution. One hour after shock or sham, the rats were inoculated with 1 x 10(8) Escherichia coli plus 1 x 10(9) Bacteroides fragilis in a fecal suspension subcutaneously. Rats were given either no antibiotic (CONTROL) or cefoxitin at 30 milligrams per kilogram (STANDARD) or 200 milligrams per kilogram (HIGH) intraperitoneally, 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes after the initial dose. STANDARD reduced abscess diameter by 58 percent compared with CONTROL in rats that were not shocked, but only by 26 percent after shock (p < 0.05 shock versus sham). HIGH further decreased abscess diameter and weight (4 +/- 1 millimeter and 22 +/- 22 milligrams) after shock compared with STANDARD (9 +/- 1 millimeter and 230 +/- 90 milligrams; both p < 0.05). Peak tissue cefoxitin levels were greater than 19 times the minimal inhibitory concentration for each bacteria for HIGH compared with eight times for STANDARD. These data demonstrate that an increased dose of cefoxitin was superior to a conventional dose in controlling a mixed gram-negative infection after shock and suggest that altering traditional antibiotic use may decrease the incidence of infection after shock and hemorrhage.