PMID- 15457367 OWN - NLM STAT- MEDLINE DCOM- 20050202 LR - 20181113 IS - 0364-2313 (Print) IS - 0364-2313 (Linking) VI - 28 IP - 8 DP - 2004 Aug TI - Dependence of positive effects of granulocyte colony-stimulating factor on the antibiotic regimen: evaluation in rats with polymicrobial peritonitis. PG - 834-44 AB - We tested the hypothesis that the ability of granulocyte colony-stimulating factor (G-CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose-response curve that was sensitive to antibiotic prophylaxis. G-CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G-CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G-CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro-inflammatory cytokine release (tumor necrosis factor-a, interleukin-6, macrophage inflammatory protein-2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G-CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G-CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here. FAU - Bauhofer, Artur AU - Bauhofer A AD - Institute of Theoretical Surgery, Philipps-University Marburg, Baldingerstrasse, 35043, Marburg, Germany. bauhofer@staff.uni-marburg.de FAU - Torossian, Alexander AU - Torossian A FAU - Lorenz, Wilfried AU - Lorenz W FAU - Middeke, Martin AU - Middeke M FAU - Plaul, Ulrike AU - Plaul U FAU - Schutz, Philipp AU - Schutz P FAU - Stinner, Benno AU - Stinner B FAU - Hattel, Markus AU - Hattel M FAU - Celik, Ilhan AU - Celik I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040803 PL - United States TA - World J Surg JT - World journal of surgery JID - 7704052 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM MH - Animals MH - *Anti-Bacterial Agents MH - Antibiotic Prophylaxis MH - Bacterial Infections/*immunology/microbiology MH - Cytokines/blood MH - Dose-Response Relationship, Drug MH - Drug Evaluation, Preclinical MH - Drug Synergism MH - Drug Therapy, Combination/*pharmacology MH - Feces/microbiology MH - Female MH - Granulocyte Colony-Stimulating Factor/*pharmacology MH - Humans MH - Inflammation Mediators/blood MH - Male MH - Neutrophils/drug effects/immunology MH - Peritonitis/*immunology/microbiology MH - Postoperative Complications/*immunology/microbiology MH - Rats EDAT- 2004/10/01 05:00 MHDA- 2005/02/03 09:00 CRDT- 2004/10/01 05:00 PHST- 2004/10/01 05:00 [pubmed] PHST- 2005/02/03 09:00 [medline] PHST- 2004/10/01 05:00 [entrez] AID - 10.1007/s00268-004-7210-1 [doi] PST - ppublish SO - World J Surg. 2004 Aug;28(8):834-44. doi: 10.1007/s00268-004-7210-1. Epub 2004 Aug 3.