title: In vivo efficacy of ceftolozane against Pseudomonas aeruginosa in a rabbit experimental model of pneumonia: comparison with ceftazidime, piperacillin/tazobactam and imipenem.
abstract: The aim of this study was to compare ceftolozane with ceftazidime, piperacillin/tazobactam (TZP) and imipenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia. Efficacy was assessed following 2 days of treatment by total colony counts in different tissues (lung, spleen and blood culture). Mean ± standard deviation pulmonary bacterial loads were 4.9 ± 0.3, 3.6 ± 0.3, 4.8 ± 0.2, 5.5 ± 0.8 and 3.9 ± 0.3 log₁₀CFU/g of lung for ceftolozane (1g), ceftolozane (2g), ceftazidime, TZP and imipenem, respectively, compared with 6.3 ± 0.9 log₁₀CFU/g of lung for control animals. The higher ceftolozane dose [2g three times daily (t.i.d.)] showed significantly better efficacy than the lower dose (1g t.i.d.). In conclusion, in this rabbit model of P. aeruginosa pneumonia, ceftolozane had an efficacy equivalent to that of comparator agents at a dose of 1g t.i.d. and had better efficacy at a higher dose (2g t.i.d.).
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France; CHU de Nantes, Pôle Hospitalo-universitaire 3, Service de Réanimation Médicale Polyvalente, Place A. Ricordeau, Nantes F-44093, France. Electronic address: cedric.bretonniere@chu-nantes.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Bretonnière
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: David
authors.initials: D
authors.lastname: Boutoille
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caillon
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Cyndie
authors.initials: C
authors.lastname: Desessard
authors.affiliation: CHU de Nantes, Pôle Hospitalo-universitaire 3, Service de Réanimation Médicale Polyvalente, Place A. Ricordeau, Nantes F-44093, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guitton
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Potel
authors.affiliation: Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, Nantes F-44035, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Jacqueline
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D002442:Ceftazidime / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077725:Piperacillin, Tazobactam Drug Combination; C519491:ceftolozane; D015378:Imipenem; D010397:Penicillanic Acid; D002442:Ceftazidime; D010878:Piperacillin
keywords: Animal model; Pharmacokinetics; β-Lactams