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A toll-like receptor 5 agonist improves the efficacy of antibiotics in the treatment of primary and influenza-associated pneumococcal mouse infections

tetano

Editor, Senior Moderator
Antimicrob Agents Chemother. 2015 Jul 20. pii: AAC.01210-15. [Epub ahead of print]
[h=1]A toll-like receptor 5 agonist improves the efficacy of antibiotics in the treatment of primary and influenza-associated pneumococcal mouse infections1.[/h] Porte R[SUP]1[/SUP], Fougeron D[SUP]1[/SUP], Mu?oz-Wolf N[SUP]2[/SUP], Tabareau J[SUP]1[/SUP], Georgel AF[SUP]3[/SUP], Wallet F[SUP]4[/SUP], Paget C[SUP]1[/SUP], Trottein F[SUP]1[/SUP], Chabalgoity JA[SUP]2[/SUP], Carnoy C[SUP]1[/SUP], Sirard JC[SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Prophylactic intranasal administration of toll-like receptor 5 (TLR5) agonist flagellin protects mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation of lung immunity might improve the therapeutic index of antibiotics in the treatment of Streptococcus pneumoniae respiratory infections in mice. Intranasal administration of flagellin was combined with either oral administration of amoxicillin or intraperitoneal injection of trimethoprim-sulfamethoxazole to treat S. pneumoniae-infected animals. Compared with standalone treatments, the combination of antibiotic and flagellin resulted in a lower bacterial load in lung and greater protection against S. pneumoniae dissemination and was associated with an early increase of neutrophil infiltration in the airways. The antibiotic-flagellin combination treatment was however not associated with any exacerbation of inflammation. Moreover, combination treatment was more efficacious than standalone antibiotic treatments in the context of post-influenza pneumococcal infection. Lastly, TLR5 signaling was shown to be mandatory for the efficacy of the combined antibacterial therapy. This study is the first to show that combining antibiotic treatment with the stimulation of mucosal innate immunity is a potent antibacterial strategy in pneumonia.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.


PMID: 26195519 [PubMed - as supplied by publisher]
 
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