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Bacterial Biofilm – Orthopaedic Considerations

- bactericidal activity and biofilm:
      - vancomycin is one of the antibiotics with intracellular bactericidal activity and therefore should cover small colony variants of staphylococci and MRSA;
              - vancomycin is a glycopeptide and may have intrinsic ability to bind to glycocalyx and penetrates glycocalices very rapidly;
              - note that with a glycocalyx formation, the MIC value (and the trough levels) will have to be higher;
              - once incorporated in biofilm Vancomycin shows a strain dependent bactericidal biofilm activity between 8 times and 128 times the MIC of planktonic bacteria;
              - shows superior bactericidal activity against biofilm embedded staphylococci and MRSA compared with most other antibiotics;
              - references:
                    - Impact of biofilm on the in vitro activity of vancomycin alone and in combination with tigecycline and rifampicin vs Staphylococcus aureus.
                    - Comparison of biofilm-associated cell survival following in vitro exposure of meticillin-resistant Staphylococcus aureus biofilms to the antibiotics clindamycin, daptomycin, linezolid, tigecycline and vancomycin.
                    - In situ measurement of linezolid and vancomycin concentrations in intravascular catheter-associated biofilm

     - staph aureus
           - Direct demonstration of viable Staphylococcus aureus biofilms in an infected total joint arthroplasty. A case report.  
      - staph epi:
           - its high recurrence rate may be related to its propensity to form a biofilm layer (extra-cellular glycocalyx) which coats the bacteria, which protects by engulfment by neutrophils;
            - slime layer may make antibiotic penetration and bacteria eradication more difficult; 
            - references:
                    - Adherence of Staphylococcus epidermidis to biomaterials is augmented by PIA.
                    - Occurrence of ica genes for slime synthesis in a collection of Staphylococcus epidermidis strains from orthopedic prosthesis infections. 
                    - Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis.
      - small colony variants:
            - may not provoke increase in CRP;
            - do not produce virulence factors 
            - culture:
                   - hemin and menadion need to be added to grow the small-colony variants (or will have false negatives);
                   - may be listed incorrectly as coagulase-negative staph;
            - small colony MIC for aminoglycoside antibiotics can be 16 times higher than for large colony types
            - slow growth and slow cell division reduces antibiotic effectiveness (antibiotics that act on cell walls);
            - small colony variants have the ability to survive in soft tissue cells;
            - antibiotics that do not affect the cell wall may be effective:
                   - tetracycline (hydrophilic antibiotic)
                   - rifampin (hydrophobic antibiotic) + cipro 
      - pseudomonas - the only gram negative that produces a biofilm layer.

- labs:
      - C-reactive protein
            - produced in the liver by cytokines - IL-6
            - staph small-colony variants do not produce virulence factors nor a-toxin  which would stimulate increase in C-reactive protein

- references:
     - Application of a rat osteomyelitis model to compare in vivo and in vitro the antibiotic efficacy against bacteria with high capacity to form biofilms. 
     - Improved aero-anaerobe recovery from infected prosthetic joint samples taken from 72 patients and collected intraop in Rosenow's broth.
     - Biofilm Theory Can Guide the Treatment of Device-Related Orthopaedic Infections
     - Is Aseptic Loosening Truly Aseptic? 
     - The Coventry Award. The value of preoperative aspiration before total knee revision.
     - Is "aseptic" loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in patients with low-grade infection?   
     - Sonication of removed hip and knee prostheses for diagnosis of infection.
     - Prior Use of Antimicrobial Therapy is a Risk Factor for Culture-negative Prosthetic Joint Infection
     - Small-Colony Variants Need Big-Time Busting 
     - Metal-on-metal bearings in total hip arthroplasties: Influence of cobalt and chromium ions on bacterial growth and biofilm formation.
     - The role of small-colony variants in failure to diagnose and treat biofilm infections in orthopedics.
     - Bacterial Adhesion: Seen Any Good Biofilms Lately?