title: Animal model methodology: immunocompetent or leucopenic rats, which is the best? Results from a model of experimental pneumonia due to derepressed cephalosporinase-producing Enterobacter cloacae.
abstract: BACKGROUND
  The aim of this study was to compare the bactericidal activity of cefepime plus amikacin against experimental pneumonia induced by a stably derepressed cephalosporinase-producing Enterobacter cloacae strain in immunocompetent and leucopenic rats.
  
  
  METHODS
  Sixty Wistar rats were used. Leucopenia was induced in half of them by a single intravenous administration of 30 mg/kg cyclophosphamide, while the remaining rats received the same volume of saline. All rats were infected 96 h later by tracheal instillation of 8 log(10) colony-forming units of E. cloacae. Twelve rats (6 immunocompetent and 6 leucopenic) were sacrificed 6 h later to assess the initial bacterial burden to the lungs. Then, the remaining 48 rats received a combination of 60 mg/kg cefepime twice a day and 25 mg/kg amikacin once a day given intraperitoneally or the same volume of saline. Six rats per group (leucopenic or not, treated or not) were sacrificed 12 and 30 h after therapy started.
  
  
  RESULTS
  Spontaneous bacterial clearance with time was observed only in immunocompetent rats. Compared to untreated animals, antibiotic administration induced a decrease in lung bacterial titres in immunocompetent and leucopenic rats. The difference was statistically significant only in leucopenic rats.
  
  
  CONCLUSIONS
  The use of leucopenic rats reduced spontaneous bacterial clearance in the lungs and increased the bactericidal effect of the antibiotic combination and ultimately the confidence in the reliability of the results.
authors.affiliation: CREPIT, CHU Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France. anne.jacolot@avc.aphp.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Jacolot
authors.forename: Claire
authors.initials: C
authors.lastname: Judel
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Chaumais
authors.forename: Kamel
authors.initials: K
authors.lastname: Louchahi
authors.forename: Patrick
authors.initials: P
authors.lastname: Nicolas
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchand
authors.forename: Olivier
authors.initials: O
authors.lastname: Petitjean
authors.forename: Olivier
authors.initials: O
authors.lastname: Mimoz
mesh_terms: D000583:Amikacin / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000077723:Cefepime; D002510:Cephalosporinase / Q000378:metabolism*; D002511:Cephalosporins / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000633:toxicity; D004359:Drug Therapy, Combination; D016972:Enterobacter cloacae / Q000201:enzymology* / Q000472:pathogenicity; D016867:Immunocompromised Host; D007274:Injections, Intraperitoneal; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D023421:Models, Animal; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077723:Cefepime; D000583:Amikacin; D003520:Cyclophosphamide; D002510:Cephalosporinase