Wednesday, February 11, 2015

Propionibacterium – What we think we know today

I. About Propionibacterium                             
   A. Slow growing Gram positive bacillus that form C02 bubbles in Swiss cheese and acne in adolescents

   B. Feed on fatty acids and produce propionic acid, hence their name
   C. Facultative anaerobes - can live in the absence or presence of atmospheric oxygen
   D. Most familiar is P. Acnes, but there are other important subtypes of Propionibacterium including P. humerusii; different subtypes may have different interactions with human host environments.
   E. SKIN IS NOT STERILE – Propionibacterium is not on us, it’s in us
      1. Part of the normal commensal flora accounting fora large portion of the skin microbiota living on and in healthy adult skin; rarely found in preadolescents
      2. Most numerous on the skin of the face, chest and back of males - the oily, not the wet environment

           3. Inhabit the relatively anaerobic sebaceous glands and hair bulbs of the dermis.

      1. FOE: Gene products include digestive enzymes and pore-forming factors that can degrade host molecules and facilitate the growth of opportunistic bacteria, such as coagulase negative Staphylococcus.
      2. FOE: May trigger insidious tissue damage (such as bone resorption leading to loosening, or capsular thickening leading to stiffness).
      3. FOE: Forms biofilms on metal, plastic, cement and in membranes surrounding implants. Biofilms are viscoelastic extracellular slime layers consisting of polysaccharides, extracellular DNA, proteins and lipids that resist detachment and can move across surfaces. These biofilms develop channels allowing for diffusion of nutrients to the embedded bacteria and provide a range of niche environments from aerobic on the surface to anaerobic at the depth. Bacteria in biofilms behave differently from those in the free-floating form and are protected from host defenses by forming conglomerates too large for inflammatory cell phagocytosis and by creating a diffusion barrier that prevents antibodies and antibiotics from reaching the bacteria. If the biofilm is disturbed, it may shed free-floating bacteria than can lead to a more obvious infection. Bacteria in biofilms are difficult to culture and difficult to eradicate. Even while embedded in a biofilm, bacteria may still induce bone resorption by activating macrophages and osteoclasts.

Strains with pili (P. Avidum, P Humerusii) seem to be better biofilm formers (see A, B, C below; D is P. Acnes with no pili).

      4. FRIEND: Close relatives of Streptomyces which have been used to produce two-thirds of the clinically useful antibiotics of natural origin, including aminoglycosides (neomycin, streptomycin), anthracyclines, chloramphenicol, macrolide, and tetracyclines.
      5. FRIEND: Modulate the host immune system, for example by inducing cutaneous interferon and interleukin-producing T cells
      6. ?FRIEND: Is the low incidence of Methicillin-resistant Staphylococcus Aureus, Streptococcus, and E. Coli infections in the shoulder (in comparison to hip and knee arthroplasty) due to a protective effect from products secreted by and enhanced host immunity induced by Propionibacterium?

II. Propionibacterium and shoulder arthroplasty
      1. The most common bacterium to be recovered at surgical revision of a failed arthroplasty
      2. Also seen after failed fracture fixation, failed cuff repair, and Latarjet procedures
      3. Risk Factors for Propionibacterium infection include male sex, young age, reverse total shoulder, arthroplasty for trauma and prior surgery or prior injection.

III. Preventing Propionibacterium from entering the surgical field
      1. Skin preparation cannot sterilize the dermis
      2. Skin incisions must transect hair bulbs and sebaceous glands containing Propionibacterium.
      3. First time shoulder surgery wounds (including scopes) can be culture positive for Propionibacterium in spite of surgical skin preparation and systemic antibiotics.
      1. Assure the skin of the extremity is healthy before taking patient to the OR
      2. Pre-incision IV Prophylaxis with Ceftriaxone 2 gm X 1 and Vancomycin 1 gm q 12 h X 2
      3. Careful preparation and draping to minimize surgical contact with skin surface onto which Propionibacterium flow from the dermal glands
      4. Discard skin knife
      5. Consider using hot knife for dermal incision to cauterize the exposed surface
      6. Minimize contact of surgical tools and implants with wound edge
      7. Minimize open wound time
      8. Copious irrigation with saline containing Ceftriaxone and Vancomycin (dilution is the solution to pollution)
      9. Handle the prosthesis in a way that avoids contact with the skin edge
      10. Avoid drains (= two way street)
      11. Personal exhaust (space) suits do not address the risk of Propionibacterium from the patient's skin.

IV. Clinical presentation of Propionibacterium infection
      1. Propionibacterium exerts its effects by enzymatic and chemical means, rather by inciting the inflammatory response we’re used to looking for
      2. Because Propionibacterium does not usually incite inflammation, the CBC, ESR, CRP, interleukin-6, joint aspiration, white cells/high power field, gram stain, are -  more often than not – normal and calor, rubor, dolor and tumor are absent
      3. Propionibacterium infections may present months or years after the index arthroplasty with symptoms of unexplained pain, stiffness or component loosening appearing long after the usual ‘worry period’ for infection is over. YOU SNOOZE, YOU LOSE.
      4. Perhaps the best suggestion of a Propionibacterium infection is the history of an initially successful arthroplasty with good recovery of comfort and function that is followed by an otherwise unexplained increase in pain and stiffness.
      5. Suspicion of Propionibacterium infection should be heightened in male patients who develop delayed problems with otherwise unexplained stiffness, pain, component loosening, or osteolysis.
      6. POSITIVE CULURES ARE NOT ‘UNEXPECTED’ IN REVISION ARTHROPLASTY. Almost 50% of revisions for failed shoulder arthroplasty have positive deep cultures, most of which are positive for Propionibacterium. In spite of having performed hundreds of these cases, I still can’t tell which ones will have floridly positive tissue and explant cultures for Propionibacterium. Of course, those shoulders with cloudy fluid, osteolysis, periprosthetic membrane, and component loosening are more likely to be culture positive.

V. Recovering Propionibacterium from surgical sites. THE USUAL ROUTINE WILL MISS THEM.
   A. There a many reasons that Propionibacterium in the tissue and explants may be overlooked in revision arthroplasty surgery, leading to the mistaken diagnosis of ‘aseptic’ failure
      1. Cultures may not be sent
      2. Multiple cultures of tissue and hardware may not be sent (TAKE FIVE)
      3. Cultures may not be observed for at least 17 days
      4. Specimens may not be submitted for culturing on aerobic and anaerobic media
      5. Preoperative antibiotics may suppress growth in culture
   B. Bacteria in biofilms may be difficult to recover
      1. Joint fluid aspiration can miss the presence of bacteria concealed in a biofilm
      2. Bacteria in biofilms may transform to a dormant or slow growing phenotype that is not revealed in cultures.
      3. Bacteria in biofilms may not be dislodged from the prosthesis by conventional culturing methods. Sonication may help.
      4. Endonucleases and other host factors may prevent the Propionibacterium from growing.
   C. Can other methods help?
      1. Broad-range 16S rRNA gene multiplex PCR
      2. Immunohistology

VI. Treating Propionibacterium infections. GO RED IF YOU WANT THEM DEAD.
A.   Difficult or impossible for antibiotics to kill Propionibacterium in a biofilm. Surest way is prosthesis exchange. Retaining a biofilm-coated implant may predispose the shoulder to persistent infection
B.    The decision between the ‘yellowprotocol’ (prosthesis retention, oral Augmentin until cultures are finalized) and the ‘red protocol’ (single stage exchange of all components, PICC line, six weeks of IV Ceftriaxone and Vancomycin, possible addition of Rifampin until culture results finalized, one year oral Augmentin) needs to be made at surgery before culture results are known.
C.    Single stage exchange appears to be effective without the obligatory return to the OR that comes with the use of a spacer. New humeral component is fixed by impaction grafting with Vancomycin – soaked cancellous allograft.
D.   Two-stage exchange with a temporary spacer is complication-ladened and appears unnecessary.
E.    If cultures are negative at three weeks, antibiotics are discontinued. If cultures are positive, our infectious disease service will advise Ceftriaxone and/or Vancomycin, possibly with Rifampin.
F.    We do not routinely use Clindamycin because of increasing Propionibacterium resistance and the heightened risk of Clostridium difficile colitis
VII. How do we know if the treatment worked? ONLY IN THE FULLNESS OF TIME.
A.   Since the presence of Propionibacterium cannot be reliably detected without open tissue biopsies and since the clinical symptoms of persistent infection may take years to manifest themselves, the success or failure of treatment cannot be known with confidence.
B.    The surest evidence of treatment failure is if the patient comes to a second revision at which Propionibacterium are again recovered.
C.    We can be relatively confident that the treatment has been successful if the patient has durable restoration of the comfort and function of the revised shoulder.
D.   The problem is that there are many patients who have incomplete restoration of comfort and function after the surgical revision of a failed shoulder arthroplasty and we cannot know if the residual problems are due to persistent infection or to other non-infectious issues with the soft tissues, the bone or the implants.
E.    We wish we had a surefire way to answer the patient’s question “after all this treatment, how do I know that the infection is cured?”

VIII. Relevant References from the University of Washington

Consultation for those who live a distance away from Seattle.

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