title: Experimental model for treatment of extended spectrum betalactamase producing-Klebsiella pneumoniae.
abstract: BACKGROUND
  Animal models are useful to evaluate the efficacy of antimicrobials in experimental sepsis.
  
  
  OBJECTIVE
  To elucidate the steps of producing an experimental model for the treatment of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sepsis
  
  
  METHODS
  Several ESBL inoculums ranging from 1.5x109 colony-forming units per milliliter (CFU/mL) to 2.0x1010 CFU/mL were administered by peritoneal injection in adults Wistar rats. Outcomes and microbiological data of quantitative peritoneal and blood cultures were observed in untreated animals. Animals which received 2.0x1010 CFU/mL inoculums were treated with single meropenem dose (30mg/kg) after one hour and those which received 1.0x1010 CFU/mL inoculums were treated immediately with three doses of meropenem 50 mg/kg. Outcomes were observed for 24 hours after inoculation.
  
  
  RESULTS
  Solutions with 1.5 x109 and 6.0x109 CFU/mL were not lethal within 24 hours. Inoculums of 1.0x1010 CFU/mL were lethal in 80% and solutions with 2.0x1010 CFU/mL were lethal in 100% of animals. ESBL lethal sepsis (1.0x1010CFU/mL) was treated immediately with 50 mg/kg of meropenem every eight hours for 24 hours and presented 40% mortality compared with 80% mortality of the control group (p=0.033). Quantitative cultures of peritoneal fluid presented 104 CFU/mL or less for treated animals compared to more than 105 for untreated animals (p=0.001).
  
  
  CONCLUSIONS
  Inoculums of 1.0x1010CFU/mL achieved the best results to study a model of lethal sepsis and this model of treatment of carbapenem-susceptible Enterobacteriaceae can serve as control to further evaluation of treatment of carbapenemase-producing Enterobacteriaceae models.
authors.affiliation: Department of Medicine, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Paula Virginia Michelon
authors.initials: PV
authors.lastname: Toledo
authors.affiliation: Department of Medicine, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Felipe Francisco
authors.initials: FF
authors.lastname: Tuon
authors.affiliation: Department of Pharmacy and Biochemistry, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Bail
authors.affiliation: Department of Pharmacy and Biochemistry, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Francine
authors.initials: F
authors.lastname: Manente
authors.affiliation: Department of Medicine, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Polliane
authors.initials: P
authors.lastname: Arruda
authors.affiliation: Department of Medicine, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
authors.forename: Ayrton Alves
authors.initials: AA
authors.lastname: Aranha-Junior
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy*; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000890:Anti-Infective Agents; D001618:beta-Lactamases