title: Differential effects of antibiotics in combination with G-CSF on survival and polymorphonuclear granulocyte cell functions in septic rats.
abstract: BACKGROUND
  In addition to their antimicrobial activity, antibiotics modulate cellular host defence. Granulocyte-colony stimulating factor (G-CSF) is also a well known immunomodulator; however little is known about the interactions of G-CSF with antibiotics. We investigated in septic rats the effects of two antibiotic combinations with G-CSF.
  
  
  METHODS
  In two clinic modelling randomised trials (CMRTs), male Wistar rats were anesthetized, given antibiotic prophylaxis, had a laparotomy with peritoneal contamination and infection (PCI), and were randomly assigned (n = 18 rats/group) to: 1) PCI only; 2) PCI+antibiotic; and, 3) PCI+antibiotic+G-CSF prophylaxis (20 mug/kg, three times). This sequence was conducted first with 10 mg/kg coamoxiclav, and then with ceftriaxone/metronidazole (Cef/met, 10/3 mg/kg). In additional animals, the blood cell count, migration and superoxide production of PMNs, systemic TNF-alpha and liver cytokine mRNA expression levels were determined.
  
  
  RESULTS
  Only the combination coamoxiclav plus G-CSF improved the survival rate (82 vs. 44%, p < 0.001). Improved survival with this combination was accompanied by normalised antimicrobial PMN migratory activity and superoxide production, along with normalised systemic TNF-alpha levels and a reduced expression of TNF-alpha and IL-1 in the liver.
  
  
  CONCLUSIONS
  There are substantial differences in the interaction of antibiotics with G-CSF. Therefore, the selection of the antibiotic for combination with G-CSF in sepsis treatment should be guided not only by the bacteria to be eliminated, but also by the effects on antimicrobial functions of PMNs and the cytokine response.
authors.affiliation: Institute of Theoretical Surgery, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany. a-bauhofer@web.de
authors.forename: Artur
authors.initials: A
authors.lastname: Bauhofer
authors.forename: Markus
authors.initials: M
authors.lastname: Huttel
authors.forename: Wilfried
authors.initials: W
authors.lastname: Lorenz
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Alexander
authors.initials: A
authors.lastname: Torossian
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D019072:Antibiotic Prophylaxis; D002443:Ceftriaxone / Q000008:administration & dosage; D002633:Chemotaxis; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005243:Feces / Q000382:microbiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006098:Granulocytes / Q000502:physiology*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D018805:Sepsis / Q000276:immunology* / Q000517:prevention & control*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D008795:Metronidazole; D016179:Granulocyte Colony-Stimulating Factor; D019980:Amoxicillin-Potassium Clavulanate Combination; D002443:Ceftriaxone