Skip Standard Navigation Links
Centers for Disease Control and Prevention
 CDC Home Search Health Topics A-Z
peer-reviewed.gif (582 bytes)
eid_header.gif (2942 bytes)
Past Issue

Vol. 8, No. 9
September 2002
 EID Home | Ahead of Print | Past Issues | EID Search | Contact Us | Announcements | Suggested Citation


Resistance to Antimicrobial Agents
Production of Endotoxins
Resistance to Host Immune System Clearance
References

Perspective

Biofilms: Microbial Life on Surfaces

Appendix I: Detachment Cells or Biofilm Aggregates

Rodney M. Donlan*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA


As already discussed, cells are routinely detached from biofilms. Sloughing and erosion may also result in aggregates of cells being shed by the biofilm. This may be particularly acute for persons with colonized indwelling medical devices such as central venous catheters. Raad et al. (1) quantified biofilms on central venous catheters and determined the relationship between biofilm formation and catheter-related septicemia. A characteristic of infective endocarditis, a biofilm process on native heart valves, is the production of emboli (cells or clumps of cells and associated platelets, fibrin, and erythrocytes). These emboli may cause serious complications when they are released into the bloodstream. Pathogenic organisms in potable water biofilms might also detach as aggregates, and, especially for those organisms with a low infective dose, consumption or exposure to water containing these organisms might result in infection. Epidemiologic evidence for this process is lacking, however.

Resistance to Antimicrobial Agents

Biofilms are highly resistant to most antimicrobial agents and disinfectants (2). In addition, organisms within biofilms can readily acquire resistance through the transfer of resistance plasmids. Such resistance could be especially acute in the health-care environment for patients with colonized urinary catheters and collection bags. Many of the enteric organisms shown to colonize urinary catheters carry plasmids encoding resistance to multiple antimicrobial agents (3). Transfer of plasmids within biofilms has been well established (as already discussed). Resistant organisms such as methicillin-resistant Staphylococcus aureus have also been shown to form biofilms (4).

Production of Endotoxins

Gram-negative bacteria within biofilms of indwelling medical devices will produce endotoxins. Production of such toxins could be especially relevant for hemodialysis patients, since endotoxins from dialysate may be transported across the dialysis membrane of the dialyzer. Vincent et al. (5) measured endotoxin levels on hemodialysis tubing and showed a correlation with bacterial biofilm counts. Other studies have also measured endotoxin levels of biofilms (6,7). However, the kinetics of endotoxin release from biofilms has not been documented.

Resistance to Host Immune System Clearance

Evidence has been provided to support the hypothesis that microorganisms detaching from biofilms on indwelling medical devices could overcome the host immune system and cause an infection. Ward et al. (8) showed that the immune system of a vaccinated rabbit had no effect (in terms of phagocytosis) on the growth of bacteria in a biofilm on an implanted peritoneal device in the animal. The vaccinated animals had a 1,000-fold higher titer of the antibody than did nonvaccinated animals, but the antibodies apparently did not reach the surface of the bacterial cells within the biofilm. Shiau and Wu (9) showed that the extracellular polymeric substance matrix produced by S. epidermidis interfered with macrophage phagocytic activity. Meluleni et al. (10) found that opsonic antibodies made by patients with chronic cystic fibrosis were unable to mediate phagocytosis and eliminate bacterial cells growing in biofilm microcolonies. Yasuda et al. (11) showed that resuspended biofilm cells of Escherichia coli were less sensitive to the killing activity of human polymorphonuclear leukocytes (PMNL) in vitro and suggested that this was due to resistance of the biofilm organisms to the active oxygen species produced by the PMNL. This indicates that cells detaching from biofilms in indwelling medical devices may have the ability to survive the PMNL phagocytic activity in the bloodstream to initiate a bloodstream infection.  

References

  1. Raad II, Sabbagh MF, Rand KH, Sherertz RJ. Quantitative tip culture methods and the diagnosis of central venous catheter-related infections. Diagn Microbiol Infect Dis 1992;15:13–20.
  2. Donlan RM. Role of biofilms in antimicrobial resistance. ASAIO J 2000;46:S47–S52.
  3. Sedor J, Mulholland SG. Hospital acquired urinary tract infections associated with the indwelling catheter. Urol Clin North Am 1999;26:821–8.
  4. Murga R, McAllister S, Miller JM, Tenover F, Bell M, Donlan RM. Effect of vancomycin treatment of methicillin-resistant S. aureus (MRSA) biofilms on central venous catheters in a model system. Poster No. C276 presented at the 2001 American Society for Microbiology Annual Meeting, Orlando, FL, May 23, 2001.
  5. Vincent FC, Tibi AR, Darbord JC. A bacterial biofilm in a hemodialysis system. Assessment of disinfection and crossing of endotoxin. ASAIO Transactions 1989;35:310–3.
  6. Holland SP, Mathias RG, Morck DW, Chiu J, Slade SG. Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms. Opthalmology 2000;107:1227–34.
  7. Rioufol C, Devys C, Meunier G, Perraud M, Goullet D. Quantitative determination of endotoxins released by bacterial biofilms. J Hosp Infect 1999;43:203–9.
  8. Ward KH, Olson ME, Lam K, Costerton JW. Mechanisms of persistent infection associated with peritoneal implants. J Med Microbiol 1992;36:406–3.
  9. Shiau A-L, Wu C-L. The inhibitory effect of Staphylococcus epidermidis slime on the phagocytosis of murine peritoneal macrophages is interferon-independent. Microbiol Immunol 1998;42:33–40.
  10. Meluleni GJ, Grout M, Evans DJ, Pier GB. Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients. J Immunol 1995;155:2029–38.
  11. Yasuda H, Ajiki Y, Aoyama J, Yokota T. Interaction between human polymorphonuclear leucocytes and bacteria released from in vitro bacterial biofilm models. J Med Microbiol 1994;41:359–67.
   
     
   
Comments to the Authors
Address for correspondence: Rodney M. Donlan, Biofilm Laboratory, Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Mailstop C16, 1600 Clifton Road, N.E., Atlanta, GA 30333, USA; fax: 404-639-3822; e-mail: rld8@cdc.gov

Comments to the EID Editors
Please use this form to submit comments to the EID Editors.

Email (optional)


 

EID Home | Top of Page | Ahead-of-Print | Past Issues | Suggested Citation | EID Search | Contact Us | Accessibility | Privacy Policy Notice | CDC Home | CDC Search | Health Topics A-Z

This page posted August 5, 2002
This page last reviewed August 5, 2002

Emerging Infectious Diseases Journal
National Center for Infectious Diseases
Centers for Disease Control and Prevention