This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Cannon, C. L.
Right arrow Articles by Youngs, W. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cannon, C. L.
Right arrow Articles by Youngs, W. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2009, p. 3285-3293, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00314-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro and Murine Efficacy and Toxicity Studies of Nebulized SCC1, a Methylated Caffeine-Silver(I) Complex, for Treatment of Pulmonary Infections {triangledown}

Carolyn L. Cannon,1* Lisa A. Hogue,1 Ravy K. Vajravelu,1 George H. Capps,1 Aida Ibricevic,2 Khadijah M. Hindi,1 Aysegul Kascatan-Nebioglu,3 Michael J. Walter,2 Steven L. Brody,2,{dagger} and Wiley J. Youngs3,{dagger}

Departments of Pediatrics,1 Medicine, Washington University School of Medicine, St. Louis, Missouri 63110-1002,2 Department of Chemistry, University of Akron, Akron, Ohio 44325-36013

Received 6 March 2009/ Returned for modification 22 April 2009/ Accepted 1 May 2009

The expanding clinical challenge of respiratory tract infections due to resistant bacteria necessitates the development of new forms of therapy. The development of a compound composed of silver coupled to a methylated caffeine carrier (silver carbene complex 1 [SCC1]) that demonstrated in vitro efficacy against bacteria, including drug-resistant organisms, isolated from patients with respiratory tract infections was described previously. The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture. Thus, it was hypothesized that SCC1 could be administered by the aerosolized route to concentrate delivery to the lung while minimizing systemic toxicity. In vivo, aerosolized SCC1 delivered to mice resulted in mild aversion behavior, but it was otherwise well tolerated and did not cause lung inflammation following administration over a 5-day period. The therapeutic efficacy of SCC1 compared to that of water was shown in a 3-day prophylaxis protocol, in which mice infected with a clinical strain of Pseudomonas aeruginosa had increased survival, decreased amounts of bacteria in the lung, and a lower prevalence of bacteremia. Similarly, by using an airway infection model in which bacteria were impacted in the airways by agarose beads, the administration of SCC1 was significantly superior to water in decreasing the lung bacterial burden and the levels of bacteremia and markers of airway inflammation. These observations indicate that aerosolized SCC1, a novel antimicrobial agent, warrants further study as a potential therapy for bacterial respiratory tract infections.

* Corresponding author. Mailing address: Department of Pediatrics, Campus Box 8208, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110-1002. Phone: (314) 286-2954. Fax: (314) 286-2895. E-mail: cannon_c{at}kids.wustl.edu

{triangledown} Published ahead of print on 18 May 2009.

{dagger} Shared last author.

Antimicrobial Agents and Chemotherapy, August 2009, p. 3285-3293, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00314-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»