Effects of G-CSF and antibiotic prophylaxis in a 2 x 2 factorial design on outcome in septic rats.

Abstract

In a recently completed randomised clinical trial in patients with colorectal cancer resections the combination of the granulocyte-colony stimulating factor (G-CSF) + cefuroxime/ metronidazole (cef/met) was superior to ofloxacin/metronidazole (ofl/met). These combinations were used to confirm the clinical data and to validate the concept of clinic modelling randomised trials (CMRTs) in a rat model of intra-abdominal sepsis. 80 male Wistar rats were randomised in a 2 x 2 factorial study design. All animals (n = 20/group) received anaesthesia, antihistamines, antibiotic prophylaxis, peritoneal contamination and infection. Groups were: 1) G-CSF + cef/met; 2) placebo + cef/ met; 3) G-CSF+ofl/met; 4) placebo + ofl/met. G-CSF (20 g/kg) prophylaxis was applied three times. Survival at 120 h was analysed with the Kaplan Meier method. Survival rate was best in the G-CSF + cef/met group with 75% and was significantly improved compared to the cef/met placebo group, in which only 42% survived (P < 0.05). Survival rate between both G-CSF groups was similar being 75% in the cef/met and 72% in the ofl/met group. P = 0.10). Ozone increased TNF-alpha and MIP-2 after infection: 127 +/- 23 pg/ml and 94 +/- 19 pg/ml (control group: 398 pg/ml and 369 pg/ml; P < 0.002 and P < 0.01). IL-6 levels were similar in both groups. The results of this CMRT confirmed the result of our clinical G-CSF trial in that G-CSF prophylaxis was most efficacious in combination with cef/met to improve the outcome.