More is better. Antibiotic management after hemorrhagic shock

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 10(6), 10(8) or 10(10) Staphylococcus 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 10(6) inoculum, SHORT was effective in both shocked and unshocked animals. In the 10(10) 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 10(8) inoculum, SHORT was effective in reducing abscess number, diameter, and weight (all p less than 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 less than 0.05). After shock, both MEGA and MEGA-LONG reduced abscess number (p less than 0.05 vs. control) and MEGA-LONG was superior to all other regimens at the 10(8) 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.