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Dr. Sujit Kumar Singh
PG- Orthopedics
PGIMS, Rohtak
In the Beginning…
 Bacteria first appeared
on earth about 3.6 billion
years ago, long before
the appearance of Homo
sapiens around 100,000
years ago..
ANTONIE van LEEUWENHOEK
What is BIOFILM?
 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 ‘slime’, is a polymeric jumble of DNA,
proteins and polysaccharides.
 If there is moisture, there is Biofilm
- Coghlan 1996
Mechanism of formation
 Biofilm formation proceeds as a four-step process:
 (1) initial attachment of bacterial cells
 (2) cell aggregation and accumulation in multiple cell
layers
 (3) biofilm maturation and
 (4)detachment of cells from the biofilm into a
planktonic state to initiate a new cycle of biofilm
formation elsewhere.
Initially-relatively unstable and susceptible to host
defenses
Later – more stable and resistant to elimination
Same yet Different
 Bacteria found in Biofilm differ from their
counterparts found freely as they are more co-
operative and interactive – Quorum Sensing
 much greater resistance to antimicrobial killing
than do planktonic bacteria
Role of Biofilm
•Infection associated with prosthetic joints
•structural and functional heterogeneity, resembling multicellular
organisms
•cell-to-cell signalling molecules is sufficient to activate genes
involved in biofilm production, a phenomenon called quorum
sensing
•protected from antimicrobial agents and host immune responses.
•greater resistance to antimicrobial killing than do planktonic
bacteria
WHY IMPLANTS
 Foreign body impairs local host defense
 Granulocytes are frustrated
 Foreign body decreases the minimum abscess forming
dose
 Biofilms further protects from Phagocytosis
Why Antibiotic are ineffective
 MIC is raised manyfolds
 Concentration gradient of antibiotics
 Delay in accumulation
 Matrix itself binds antibiotics
 Antibiotic conc. May never reach sufficient levels
 Beta-lactamase released in small vesicles
 Upregulation of efflux pumps
In contrast to most other infections, there is no
spontaneous healing of implant-associated
infections. Such infections persist until the
device is either spontaneously expulsed or
surgically removed.
Even therapy with antibiotics to which the
microorganism is highly susceptible does often
not eliminate the biofilm from the surface of an
implanted device. Therefore, until recently, it
has been a dogma that infections around a
foreign body cannot be cured.
Treatment
 Combination of Antimicrobials
 Iv route
 Minimizes the risk of emergence of resistance
 No concensus on the duration of treatment
 Surgical treatment
-debridement with retention
-one stage exchange
-two stage exchange with a short/long interval
-long term suppressive antimicrobial treatment
-implant removal without replacement
Surgical Treatment
 Embedding of antimicrobial substances in
nanoceramics (Simchi et al., 2011).
 For local delivery of cationic antimicrobial peptides, a
thin layer of micro-porous calcium phosphate has
been used (Kazemzadeh-Narbat et al., 2010).
 Antibiotic coated implants
 Vaccination against staphylococcal biofilms.
However, identification of a relevant antigen that is
present in the planktonic and biofilm state of most
clinical strains is the limiting factor(Harro et al., 2010).
Other modalities
Recent advances
 Quorum Sensing is crucial for survival of biofilm
bacteria.
 The quorum sensing inhibitor RNAIII-inhibiting
peptide (RIP) has been evaluated in vitro and in vivo.
 In a rat model, RIP coating to bone cement beads
prevented S. aureus infection (Anguita-Alonso et al.,
2007). However, therapeutic efficacy of this concept
has not yet been shown clinically.
Thank You

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Biofilms

  • 1. Dr. Sujit Kumar Singh PG- Orthopedics PGIMS, Rohtak
  • 2.
  • 3. In the Beginning…  Bacteria first appeared on earth about 3.6 billion years ago, long before the appearance of Homo sapiens around 100,000 years ago.. ANTONIE van LEEUWENHOEK
  • 4. What is BIOFILM?  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 ‘slime’, is a polymeric jumble of DNA, proteins and polysaccharides.  If there is moisture, there is Biofilm - Coghlan 1996
  • 5. Mechanism of formation  Biofilm formation proceeds as a four-step process:  (1) initial attachment of bacterial cells  (2) cell aggregation and accumulation in multiple cell layers  (3) biofilm maturation and  (4)detachment of cells from the biofilm into a planktonic state to initiate a new cycle of biofilm formation elsewhere. Initially-relatively unstable and susceptible to host defenses Later – more stable and resistant to elimination
  • 6.
  • 7. Same yet Different  Bacteria found in Biofilm differ from their counterparts found freely as they are more co- operative and interactive – Quorum Sensing  much greater resistance to antimicrobial killing than do planktonic bacteria
  • 8. Role of Biofilm •Infection associated with prosthetic joints •structural and functional heterogeneity, resembling multicellular organisms •cell-to-cell signalling molecules is sufficient to activate genes involved in biofilm production, a phenomenon called quorum sensing •protected from antimicrobial agents and host immune responses. •greater resistance to antimicrobial killing than do planktonic bacteria
  • 9. WHY IMPLANTS  Foreign body impairs local host defense  Granulocytes are frustrated  Foreign body decreases the minimum abscess forming dose  Biofilms further protects from Phagocytosis
  • 10. Why Antibiotic are ineffective  MIC is raised manyfolds  Concentration gradient of antibiotics  Delay in accumulation  Matrix itself binds antibiotics  Antibiotic conc. May never reach sufficient levels  Beta-lactamase released in small vesicles  Upregulation of efflux pumps
  • 11. In contrast to most other infections, there is no spontaneous healing of implant-associated infections. Such infections persist until the device is either spontaneously expulsed or surgically removed. Even therapy with antibiotics to which the microorganism is highly susceptible does often not eliminate the biofilm from the surface of an implanted device. Therefore, until recently, it has been a dogma that infections around a foreign body cannot be cured.
  • 12.
  • 13.
  • 14. Treatment  Combination of Antimicrobials  Iv route  Minimizes the risk of emergence of resistance  No concensus on the duration of treatment  Surgical treatment -debridement with retention -one stage exchange -two stage exchange with a short/long interval -long term suppressive antimicrobial treatment -implant removal without replacement
  • 16.
  • 17.  Embedding of antimicrobial substances in nanoceramics (Simchi et al., 2011).  For local delivery of cationic antimicrobial peptides, a thin layer of micro-porous calcium phosphate has been used (Kazemzadeh-Narbat et al., 2010).  Antibiotic coated implants  Vaccination against staphylococcal biofilms. However, identification of a relevant antigen that is present in the planktonic and biofilm state of most clinical strains is the limiting factor(Harro et al., 2010). Other modalities
  • 18. Recent advances  Quorum Sensing is crucial for survival of biofilm bacteria.  The quorum sensing inhibitor RNAIII-inhibiting peptide (RIP) has been evaluated in vitro and in vivo.  In a rat model, RIP coating to bone cement beads prevented S. aureus infection (Anguita-Alonso et al., 2007). However, therapeutic efficacy of this concept has not yet been shown clinically.