Treatment of intra-abdominal infection with granulocyte colony-stimulating factor.
Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002432:Cecum; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007239:Infections / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007416:Intestinal Perforation / Q000150:complications*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015996:Survival Rate; D013997:Time Factors
D005839:Gentamicins; D016179:Granulocyte Colony-Stimulating Factor