Efficacy of ceftolozane in a murine model of Pseudomonas aeruginosa acute pneumonia: in vivo antimicrobial activity and impact on host inflammatory response.

Abstract

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.

• Authors: Cédric Jacqueline, Antoine Roquilly, Cyndie Desessard, David Boutoille, Alexis Broquet, Virginie Le Mabecque, Gilles Amador, Gilles Potel, Jocelyne Caillon, Karim Asehnoune
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 68 Issue 1 Pg. 177-83 (Jan 2013) ISSN: 1460-2091 [Electronic] England
• PMID: 22941899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Cephalosporins
• Ceftazidime

Topics

• Acute Disease
• Animals
• Anti-Infective Agents (pharmacology, therapeutic use)
• Ceftazidime (pharmacology, therapeutic use)
• Cephalosporins (pharmacology, therapeutic use)
• Disease Models, Animal
• Drug Resistance, Multiple, Bacterial (drug effects)
• Inflammation (drug therapy, microbiology, pathology)
• Mice
• Microbial Sensitivity Tests (methods)
• Pneumonia, Bacterial (drug therapy, pathology)
• Pseudomonas Infections (drug therapy, pathology)
• Pseudomonas aeruginosa (drug effects, growth & development)
• Treatment Outcome