| Efficacy of ceftolozane in a murine model of Pseudomonas aeruginosa acute pneumonia: in vivo antimicrobial activity and impact on host inflammatory response. | |
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MedLine Citation:
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PMID: 22941899 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVES: 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. |
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Authors:
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Cédric Jacqueline; Antoine Roquilly; Cyndie Desessard; David Boutoille; Alexis Broquet; Virginie Le Mabecque; Gilles Amador; Gilles Potel; Jocelyne Caillon; Karim Asehnoune |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-30 |
Journal Detail:
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Title: The Journal of antimicrobial chemotherapy Volume: - ISSN: 1460-2091 ISO Abbreviation: J. Antimicrob. Chemother. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-9-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7513617 Medline TA: J Antimicrob Chemother Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Université de Nantes, Faculté de Médecine, Thérapeutiques Cliniques et Expérimentales des Infections, EA 3826, F-44000 Nantes, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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