Biofilm

Definition
• A Biofilm is an assemblage of surface-associated microbial cells that is
enclosed in an extracellular polymeric substance (EPS) matrix
• Biofilm EPS is also referred to as “slime”, which is a polymeric jumble
of DNA, proteins and polysaccharides
How does a Biofilm form?
• Biofilm formation follows four steps:
• Initial attachment of bacterial cells
• Cell aggregation and accumulation in multiple cell layers
• Biofilm Maturation
• Detachment of cells from biofilm into a planktonic state to initiate
a new cycle of biofilm formation
• Biofilms are initially unstable and susceptible to host
defenses then become more stable and resistant to
elimination once mature
Biofilm in relation to Orthopedics
• Infection associated with prosthetic joints
• Structural and functional heterogeneity, resembling multicellular
organisms
• Cell-to-cell signalling molecules are sufficient to activate genes
involved in biofilm production, a phenomenon called quorum sensing
• The biofilm state offers protection from antimicrobial agents and host
immune responses
• Greater resistance to antimicrobial killing than planktonic bacterium
Biofilm vs Planktonic
• Bacteria in Biofilms are more cooperative and Interactive, which is
achieved through Quorum Sensing
• Biofilm bacterium have much greater resistance to antimicrobial
treatment than planktonic bacterium
Why are Biofilms more likely to form on
Implants than organic tissue?
• Foreign Bodies (Implants) impair local host defenses
• Granulocytes are ineffective
• The Foreign Bodies (Implants) decrease the minimum infection
required to produce an abscess
• The Biofilm state protects from phagocytosis by host defenses
Why are antibiotics ineffective at clearing
Biofilms?
• MIC is raised
• Concentration gradient of antibiotics
• Delay in accumulation of antibiotic at target
• The Biofilm Matrix itself binds to the antibiotics
• Antibiotic concentration may not reach concentration sufficient to
clear infection from implant
• Biofilm may release Beta-lactamase via small vesicles
• Upregulation of efflux pumps
Findings pertaining to infected implants
• There is no spontaneous healing of implant-associated infections
• These infections persist until the device is either spontaneously
expelled or surgically removed
• Often therapy with antibiotics to which the microorganism is highly
susceptible does not eliminate the biofilm from the surface of the
implanted device
 Cure rates of Experimental Device
Associated infections by MRSA (Zimmerli et
al 1994)
Regimen Cure rate (%)
Vancomycin 0
Teicoplanin 0
Ciprofloxacin 17
Rifampin 50
Vancomycin+Rifampin 75
Teicoplanin+Rifampin 67
Ciprofloxacin+Rifampin 92
 Cure rate of experimental device-associated
infection caused by MRSA (John et al 2009)
Regimen Cure Rate (%)
Vancomycin 0
Linezolid 0
Daptomycin 0
Rifampin 33
Vancomycin+Rifampin 8
Daptomycin+Rifampin 67
Levofloxacin+Rifampin 58
Treatment
• Combination of Antimicrobials
• IV route is more effective with regards to compliance
• Minimizes the risk or emergence of resistance
• No consensus on the duration of treatment
• Surgical treatment options:
• Debridement with implant retention
• One stage exchange
• Two stage exchange with a short/long interval
• Long term suppressive antimicrobial treatment
• Implant removal without replacement
Further treatment modalities
• Embedding of Antimicrobial substances in nanoceramics (Simchi et al
2011)
• A thin layer of micro-porous calcium phosphate for local delivery of
cationic antimicrobial peptides (Kazemzadeh-Narbat et al 2010_
• Antibiotic-coated Implants
• Vaccination against staphylococcal biofilms, however identification of
relevant antigen that is present in planktonic and biofilm state of
most clinical strains is a limiting factor for this (Harro et al 2010)
Treatment updates
• Quorum Sensing is crucial for biofilm survival
• The quorum sensing inhibitor RNAIII-inhibiting peptide (RIP) has been
evaluated in vitro and in vivo
• In a rat model, RIP coating on bone cement beads prevented S.Aureus
infection (Anguita-Alonso et al 2007) however therapeutic efficacy of
this concept has not been shown clinically
Summary
• Biofilm can be made by all bacteria
• Once established cannot be eradicated with
any antibiotic regimen alone
• Effective Treatment requires Prosthetic
removal and radical soft tissue debridement
Summary
• Infection Treatment:
• Acute: known infection <3 weeks – irrigation and
debridement, exchange of modular bearings,
component retention, and iV antibiotics
• Chronic (Biofilm state): implant removal, irrigation
and debridement, joint stabilization with antibiotic-
loaded cement spacer, IV antibiotics, and second-
stage reconstruction