More Is Better

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Abstract
Previous reports suggest that standard antibiotic prophylaxis is ineffective in reducing the incidence of wound infection after hemorrhagic shock. This study investigated the use of larger and longer doses of antibiotic in a model of staphylococcal infection after hemorrhagic shock. Sprague-Dawley rats resuscitated from hemorrhagic shock were injected with either 106, 108 or 1010Staphylococcus aureus subcutaneously. Five treatments were investigated: 1) control (no antibiotic), 2) short-course cefazolin (CEF) (SHORT), 30 mg/kg intraperitoneal (IP), 30 minutes before and 4 hours after inoculation, 3) long-course CEF (LONG), 30 mg/kg IP, 30 minutes before and 4 hours after inoculation, and thereafter, every 8 hours for 3 days, 4) mega-CEF (MEGA) 200 mg/kg IP, 30 minutes before and 4 hours after inoculation, and 5) mega-long CEF (MEGA-LONG), 200 mg/kg IP, 30 minutes before and 4 hours after inoculation, and thereafter, every 8 hours for 3 days. Abscess number, weight, and diameter were measured on Day 7. At the 106 inoculum, SHORT was effective in both shocked and unshockcd animals. In the 1010 group, all antibiotic regimens decreased the 100% mortality that followed shock without treatment, but they had little effect on abscess formation. In unshocked rats at the 108 inoculum, SHORT was effective in reducing abscess number, diameter, and weight (all p < 0.05 vs. control). After hemorrhagic shock, SHORT did not decrease abscess frequency, but it did diminish abscess diameter. LONG significantly decreased abscess diameter and abscess weight (both p < 0.05). After shock, both MEGA and MEGA-LONG reduced abscess number (p < 0.05 vs. control) and MEGA-LONG was superior to all other regimens at the 108 inoculum. These experimental data show that increasing both the dose and duration of antibiotic administration is more effective than standard short-course antibiotic prophylaxis in preventing experimental infection after hemorrhagic shock.