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


METHODS
80 male Wistar rats were randomised in a 2 x 2 factorial study design.


METHODS
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.


METHODS
Survival at 120 h was analysed with the Kaplan Meier method.


RESULTS
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.


CONCLUSIONS
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.
Bauhofer
A
A
Institute of Theoretical Surgery, University of Marburg, Baldingerstrasse, 35033, Marburg, Germany. bauhofer@staff.uni-marburg.de
Celik
I
I
Plaul
U
U
Wulf
H
H
Torossian
A
A
D000005:Abdomen; D000818:Animals; D019072:Antibiotic Prophylaxis; D002444:Cefuroxime / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D015242:Ofloxacin / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D018805:Sepsis / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D008795:Metronidazole; D016179:Granulocyte Colony-Stimulating Factor; D015242:Ofloxacin; D002444:Cefuroxime