title: Efficacy of ceftolozane in a murine model of Pseudomonas aeruginosa acute pneumonia: in vivo antimicrobial activity and impact on host inflammatory response.
abstract: OBJECTIVE
  To assess the activity of ceftolozane, a novel oxyimino-cephalosporin, in comparison with ceftazidime and piperacillin/tazobactam against a multidrug-resistant Pseudomonas aeruginosa strain using a murine model of pneumonia.
  
  
  METHODS
  Quantitative bacteriology, survival, histological examination, myeloperoxidase activity, proinflammatory cytokine levels in lungs and endothelial permeability were evaluated to determine the effects of ceftolozane and comparators on P. aeruginosa-induced pneumonia.
  
  
  RESULTS
  After 48 h of treatment, ceftolozane reduced the bacterial load by 3-4 log(10) cfu/g of lung. Systemic dissemination of the pulmonary infection and development of lung damage were inhibited in all β-lactam-treated animals. P. aeruginosa-induced pneumonia led to elevated concentrations of tumour necrosis factor-α, interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 in the lungs. While the levels of proinflammatory cytokines decreased following ceftazidime and piperacillin/tazobactam therapy, ceftolozane exhibited increased concentrations of IL-1β and MIP-2 after 24 h of infection, resulted in significantly increased levels of recruited neutrophils within the infected lung without increasing lung endothelial permeability.
  
  
  CONCLUSIONS
  These data strongly support ceftolozane as an effective option for the treatment of severe P. aeruginosa respiratory infections by improving the early pulmonary inflammatory response without impairing 48 h post-infection homeostasis.
authors.affiliation: Université de Nantes, Faculté de Médecine, Thérapeutiques Cliniques et Expérimentales des Infections, EA 3826, F-44000 Nantes, France. cedric.jacqueline@univ-nantes.fr
authors.forename: Cédric
authors.initials: C
authors.lastname: Jacqueline
authors.forename: Antoine
authors.initials: A
authors.lastname: Roquilly
authors.forename: Cyndie
authors.initials: C
authors.lastname: Desessard
authors.forename: David
authors.initials: D
authors.lastname: Boutoille
authors.forename: Alexis
authors.initials: A
authors.lastname: Broquet
authors.forename: Virginie
authors.initials: V
authors.lastname: Le Mabecque
authors.forename: Gilles
authors.initials: G
authors.lastname: Amador
authors.forename: Gilles
authors.initials: G
authors.lastname: Potel
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
mesh_terms: D000208:Acute Disease; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002442:Ceftazidime / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; D002442:Ceftazidime