Home Clean Living What we know about Cutibacterium perprosthetic infection and what about topical Vancomycin?

What we know about Cutibacterium perprosthetic infection and what about topical Vancomycin?


Several facts are well established about shoulder periprosthetic infection (PJI):

(1) Cutibacterium (formerly Propionibacterium) is the most common causative organism (see 10 points about Cutibacterium, periprosthetic infection, and revision for failed shoulder arthroplasty).

(2) The source of the Cutibacterium is the pilosebaceous glands of the patient’s dermis which are transected at the time of the skin incision.

(3) No preoperative prophylaxis (antibiotics or skin preparation) can completely prevent the inoculation of the wound with Cutibacterium.

(4) Once Cutibacterium is introduced into the wound, it can form a biofilm of the implants – this biofilm protects the bacteria from host defenses and antibiotics (see Shoulder joint infections and biofilms).

(5) Cutibacterium PJI often have a “stealth” presentation with symptoms such as delayed onset of pain and stiffness after a “honeymoon” period of satisfactory recovery.

(6) The clinical onset of Cutibacterium PJI may be months or years after the index arthroplasty.

(7) Cases of Cutibacterium PJI may not meet the criteria set forth by the Proceedings from the 2018 International Consensus Meeting on Orthopedic Infections: the definition of periprosthetic shoulder infection.

(8) The diagnosis of Cutibacterium PJI requires submitting 5 deep tissue or explant specimens for aerobic and anaerobic cultures which are observed for at least two weeks.

(9) Certain patients with painful or failed shoulder arthroplasty can be identified as having a high risk for Cutibacterium PJI by some or all of the following characteristics:

    (a) Young, healthy, males

    (b) Unexplained onset of pain and/or stiffness after a honeymoon of good postoperative function.

    (c) Substantial growth of Cutibacterium on cultures of the unprepared skin over the area of the incision (see Cutibacterium periprosthetic infection – prediction from skin cultures prior to revision arthroplasty and  Revision shoulder arthroplasty – can we predict if bacterial are present?).

    (d) High levels of serum testosterone (see Shoulder joint replacement infections – high testosterone levels may increase the risk).

    (e) Humeral component loosening (see Prognostic factors for bacterial cultures positive for Propionibacterium acnes and other organisms in a large series of revision shoulder arthroplasties performed for stiffness, pain, or loosening).

An important question is how we can reduce the risk of Cutibacterium PJI in these high risk patients. Adjunctive measures, such as Betadine lavage and a three week course of post operative oral antibiotics (doxycycline or augmentin), are often used. Another measure is topical Vancomycin. While robust clinical studies of its effectiveness are lacking, here is a bit of information on this adjunctive measure:

There is in vitro evidence of the effectiveness of topical vancomycin in preventing Cutibacterium growth. See, for example, Vancomycin is Effective in Preventing C. acnes Growth in a Shoulder Arthroplasty Mimetic. In this study the authors investigated the effect of vancomycin powder on Cutibacterium growth within the first 48 hrs. after surgery.  Cutibacterium were applied to titanium alloy foil and embedded beneath multiple layers of collagen-impregnated cellulose scaffold strips containing human shoulder joint capsular fibroblasts, facilitating the development of an oxygen gradient with an anaerobic environment around the foil and inner layers.

10 mg of vancomycin powder was applied between the Cutibacterium layer and the human cell containing scaffold strips to model direct antibiotic application and intravenous vancomycin prophylaxis was modelled by adding vancomycin in media at 5μg/mL or 20 μg/mL. 

After 48 h, the C. acnes inoculum layer was sub-cultured onto agar plates to assess the formation of viable Cutibacterium colonies. Primary human shoulder capsule cells were assessed microscopically to detect any detrimental effects of Vancomycin on cellular integrity.

Agar plates inoculated with extracts from untreated shoulder-joint implant mimetic consistently resulted in the growth of large numbers of Cutibacterium colonies, whereas treatments with vancomycin powder or vancomycin in media at 20μg/dL dilution effectively prevented the recovery of any Cutibacterium colonies. 

Vancomycin powder had no discernable short-term impact on shoulder capsule cell morphology and the presence of these cells had no discernable impact on vancomycin degradation over time.

The authors concluded that vancomycin administration effectively prevented Cutibacterium growth in a bioartificial shoulder-joint implant mimetic. These results support the hypothesis that intra incisional vancomycin application may limit Cutibacterium prosthetic joint infections.

Another paper estimated the size of reduction in PJI rate that would be necessary to justify the use of topical vancomycin, The cost effectiveness of vancomycin for preventing infections after shoulder arthroplasty: a break-even analysis These authors concluded that prophylactic administration of local vancomycin powder during shoulder arthroplasty could be highly cost-effective. They estimated that the overall cost to treat an infection is $46,745. Vancomycin costs vary from $2.50 to $44 per gram of vancomycin. At $2.50 per gram, vancomycin only needs to obtain an efficacy of 0.005% in reducing the rate of PJI to be cost-effective, whereas at $44 per gram, the efficacy needs to be 0.09% to be cost- effective. 

So, admitting that a large-scale randomized controlled trial would be necessary to determine the efficacy and safety of vancomycin in an attempt to reduce the rate of Cutibacterium PJI, the question is, “what should shoulder surgeons do while waiting for the results of such a study – use or do not use topical vancomycin?” 

An example of a Cutibacterium PJI

Here is another recent article of relevance: In vitro susceptibility of Propionibacterium acnes to simulated intrawound vancomycin concentrations 

These authors state that there is convincing evidence supporting the prophylactic use of intrawound Vancomycin powder in spinal fusion surgery and mounting evidence in the arthroplasty literature suggesting that it can reduce surgical site infections. As a result, a number of shoulder arthroplasty surgeons have adopted this practice, despite a paucity of evidence and the presence of a pathogen that is, for the most part, unique to this area of the body—Propionibacterium acnes. 

The purpose of this study was to evaluate the efficacy of vancomycin against planktonic P. acnes in vitro, using time-dependent concentrations one would expect in vivo after intra-articular application based on a prior in vivo study (see this link) in which 2 gm of Vancomycin was applied topically in arthroplasty wounds (although the Vancomycin was not applied as a powder, but rather injected through a drain). Intrawound Vancomycin concentrations were interpolated and extrapolated from these in vivo data.

Planktonic P. acnes was then subjected to a time-kill analysis during 96 hours.

At each time point, the inoculum was centrifuged into pellet form and then reconstituted for serial drop counts onto blood agar plates. After anaerobic incubation, colony-forming units were counted, and log10 colony forming units per milliliter were determined.

Early time points grew to confluence, and thus colony-forming units per milliliter were not calculated. However, at 12 hours of vancomycin treatment, distinct colonies were appreciated. There was a 3 x log10 reduction in colony-forming units per milliliter between 12 and 48 hours, denoting bactericidal activity. P. acnes was completely eradicated after 3 days of treatment.

The authors concluded that when administered in a fashion meant to simulate time-dependent in vivo intrawound concentrations, vancomycin exhibited bactericidal activity against P. acnes. 

Comment: It seems that the best chance to reduce the size of the Cutibacterium inoculum at the time of primary shoulder arthroplasty is to use agents that act against the  organism while it is in its planktonic stage, i.e. before it forms a biofilm on the implants. Although clinical support for this approach is still lacking, these studies suggest that topical Vancomycin may be an effective adjunct. Its minimum inhibitory concentration of 0.38 μg/mL while the vancomycin concentration required to eradicate and established biofilm has been estimated to be ≥128 μg/mL.

Our practice in patients at risk for Cutibacterium PJI is to use preoperative Ceftriaxone and Vancomycin intravenously, vigorous Betadine lavage, topical Vancomycin powder in the medullary canal and in the joint, and a three week course of postoperative oral antibiotics. We are following these patients closely to evaluate the effectiveness of this approach.

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