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
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.