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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Starner, T. D.
Right arrow Articles by Kim, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Starner, T. D.
Right arrow Articles by Kim, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2008, p. 137-145, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00607-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms{triangledown}

Timothy D. Starner,1* Joshua D. Shrout,2 Matthew R. Parsek,2 Peter C. Appelbaum,3 and GunHee Kim1

Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242,1 Department of Microbiology, University of Washington, Seattle, Washington 98195,2 Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 170333

Received 8 May 2007/ Returned for modification 19 August 2007/ Accepted 12 October 2007

Nontypeable Haemophilus influenzae (NTHi) commonly causes otitis media, chronic bronchitis in emphysema, and early airway infections in cystic fibrosis. Long-term, low-dose azithromycin has been shown to improve clinical outcomes in chronic lung diseases, although the mechanism of action remains unclear. The inhibition of bacterial biofilms by azithromycin has been postulated to be one mechanism mediating these effects. We hypothesized that subinhibitory concentrations of azithromycin would affect NTHi biofilm formation. Laboratory strains of NTHi expressing green fluorescent protein and azithromycin-resistant clinical isolates were grown in flow-cell and static-culture biofilm models. Using a range of concentrations of azithromycin and gentamicin, we measured the degree to which these antibiotics inhibited biofilm formation and persistence. Large biofilms formed over 2 to 4 days in a flow cell, displaying complex structures, including towers and channels. Subinhibitory concentrations of azithromycin significantly decreased biomass and maximal thickness in both forming and established NTHi biofilms. In contrast, subinhibitory concentrations of gentamicin had no effect on biofilm formation. Furthermore, established NTHi biofilms became resistant to gentamicin at concentrations far above the MIC. Biofilm formation of highly resistant clinical NTHi isolates (azithromycin MIC of >64 µg/ml) was similarly decreased at subinhibitory azithromycin concentrations. Clinically obtainable azithromycin concentrations inhibited biofilms in all but the most highly resistant isolates. These data show that subinhibitory concentrations of azithromycin have antibiofilm properties, provide mechanistic insights, and supply an additional rationale for the use of azithromycin in chronic biofilm infections involving H. influenzae.

* Corresponding author. Mailing address: Department of Pediatrics, University of Iowa, 2080H Medical Laboratories, 200 Hawkins Drive, Iowa City, IA 52242. Phone: (319) 335-7265. Fax: (319) 356-7171. E-mail: timothy-starner{at}uiowa.edu

{triangledown} Published ahead of print on 22 October 2007.

Antimicrobial Agents and Chemotherapy, January 2008, p. 137-145, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00607-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Presterl, E., Hajdu, S., Lassnigg, A. M., Hirschl, A. M., Holinka, J., Graninger, W. (2009). Effects of Azithromycin in Combination with Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms. Antimicrob. Agents Chemother. 53: 3205-3210 [Abstract] [Full Text]  
  • Foweraker, J. (2009). Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull 89: 93-110 [Abstract] [Full Text]  
  • Idris, S. F, Chilvers, E. R, Haworth, C., McKeon, D., Condliffe, A. M (2009). Azithromycin therapy for neutrophilic airways disease: myth or magic?. Thorax 64: 186-189 [Full Text]  
  • Ryan, R. P., Dow, J. M. (2008). Diffusible signals and interspecies communication in bacteria. Microbiology 154: 1845-1858 [Abstract] [Full Text]  


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