Showing posts with label Vancomycin. Show all posts
Showing posts with label Vancomycin. Show all posts

Sunday, August 25, 2024

Why use topical Vancomycin powder as infection prophylaxis in shoulder arthroplasty?

Periprosthetic infection is a serious complication of shoulder arthroplasty. The most common causative organism is Cutibacterium residing in the pilosebaceous units of the dermis overlying the shoulder. As pointed out in a recent post (see this link), these commensal organisms cannot be eradicated by skin preparation prior to making the incision for shoulder arthroplasty. The result is unavoidable contamination of the wound (see Propionibacterium can be isolated from deep cultures obtained at primary arthroplasty despite intravenous antimicrobial prophylaxis). 

Whether or not this contamination results in a periprosthetic infection depends on (1) the interaction between the host and bacterium and (2) the details of the surgical procedure: the intravenous prophylactic antibiotics used, open wound time, and the composition of the implants. Other measures may help manage the contamination before it establishes a biofilm on the implants: copious irrigation, povidone-iodine lavage and topical in-wound vancomycin. The effectiveness of these measures is difficult investigate rigorously because of the relative infrequency of Cutibacterium infections, the stealthy way in which they typically present, and - in most cases - the need to obtain deep tissue or explant specimens for cultures to determine if an infection is present.

Admitting the need for more robust evidence, let us review some of the information supportive of the use of topical vancomycin in reducing the risk of Cutibacterium periprosthetic infection. 




(1) The cost is low: if 1 to 2 grams are used, the total cost per surgery would range from $10 to $40.

(2) The risk is low:  The risks of vancomycin intravenous infusion reaction are minimized with topical use. The risks of allergy, nephrotoxity and ototoxicity are low with topical administration due to the limited systemic levels.

(3) In vitro data supportive of its effectiveness

    a) 2013 Antimicrobial Susceptibility of Propionibacterium acnes Isolates from Shoulder Surgery: Cutibacterium isolates from shoulder surgery were susceptible to vancomycin.

    b) 2017 In vitro susceptibility of Propionibacterium acnes to simulated intrawound vancomycin concentrationsWhen administered in a fashion meant to simulate time-dependent in vivo intrawound concentrations, vancomycin exhibited bactericidal activity against P. acnes [Cutibacterium].

     c) 2022 Vancomycin is effective in preventing Cutibacterium acnes growth in a mimetic shoulder arthroplastyVancomycin administration effectively prevented C acnes growth in a bioartificial shoulder joint mimetic implant.

(4) Clinical data

    a) 2011 Intrawound application of vancomycin for prophylaxis in instrumented thoracolumbar fusions.   Adjunctive local application of vancomycin powder decreased the postsurgical wound infection rate with statistical significance in posterior instrumented thoracolumbar spine fusions.

    b) 2017 The cost effectiveness of vancomycin for preventing infections after shoulder arthroplasty: a break-even analysisthe prophylactic administration of local vancomycin powder during shoulder arthroplasty is a highly cost-effective practice.

    c) 2017 Intrawound Vancomycin Powder Reduces Early Prosthetic Joint Infections in Revision Hip and Knee ArthroplastyThe use of intrawound vancomycin powder was associated with a significant reduction in the overall incidence of early PJIs following joint arthroplasty, however, only the revision procedures demonstrated a significant reduction in the rate of early PJIs.

    d) 2023 Vancomycin powder embedded in collagen sponge decreases the rate of prosthetic shoulder infectionIntrawound vancomycin powder significantly reduced the rate of periprosthetic shoulder infections without any increase in local and systemic aseptic complications at a minimum follow-up of 12 months. 

    e) 2024 Prophylactic use of vancomycin powder on postoperative infection after total joint arthroplastyThis systematic review of retrospective studies found that local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection.

Comment: Periprosthetic infection are devastating for the patient. Many variables influence a patient's risk, including sex, age, immune defenses, medications, comborbidities, prior surgery, prior injections, skin microbiome, bacterial virulence, surgical procedure, surgical time, as well as preoperative, intraoperative and postoperative prophylactic measures. Controlling for these variables to single out the clinical effectiveness of topical vancomycin in reducing infection rate would be a statistical nightmare. Laboratory data are encouraging and have the advantage of tightly controlling the variables, but they cannot duplicate the clinical situation.

Let's keep our eyes out for more light to shine on this topic.

Comments welcome at shoulderarthritis@uw.edu

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link

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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link). 


Sunday, April 2, 2023

Postoperative infections of the shoulder - demographics and prevention

Shoulder infections are important causes of failed shoulder surgery. Here is a case of a total shoulder periprosthetic infection by Cutibacterium


A number of recent publications are of interest.

I. The authors of The POSI study: gender differences in 94 cases of postoperative shoulder surgery infection: results of a 7-year retrospective multicenter study reported the characteristics of patients experiencing postoperative shoulder infections. A confirmed shoulder infection was defined as 2 positive cultures or more of the same microorganism, or clear clinical infection with 1 positive culture.

The mean patient age at index surgery was 59 years (range: 22-91) with a majority being men (74%). Arthroplasty was the most common index surgery, followed by fracture fixation, arthroscopic surgery, and other open procedures.

The median time between the index surgery and the first positive sample was 5 months (mean 23 months, minimum 6 days to maximum 27 years). The median time between index surgery and diagnosis for cases with Cutibacterium infections was 8.6 months in contrast to 3.9 months for other organisms.

Cutibacterium species were identified in 64 patients (68%), 59 of which were Cutibacterium acnes (63%). In 86% of cases, Cutibacterium was identified at the first revision. The other 2 most common germs were Staphylococcus epidermidis and Staphylococcus aureus, (29% and 17%, respectively). Polymicrobial infection was present in 30% of patients.

Cutibacterium was twice as frequent in men.
S. epidermidis was twice as frequent in women.
S. epidermidis was 3 times more prevalent in chronic than in acute cases.

Comment: Of note: (1) the long intervals between the index procedure and diagnosis, especially for Cutibacterium infections, (2) the sex difference in frequency of Cutibacterium and S. epidermidis, and (3) 5 of the 64 Cutibacterium infections were by species other than C. acnes.

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II. What is the best IV prophylaxis against shoulder infections? As detailed in this link, cephalosporin antibiotics are most effective in preventing shoulder infections from the two most common causative organisms: Cutibacterium and coagulase negative Staphylococcus. This link also addresses the situation in which the patient reports a penicillin allergy. 

Patients with penicillin "intolerance" history
and patients with low risk penicillin allergy history
can be given cephalosporins with low risk of reactions. Whereas patients with high risk history of penicillin allergy

shoulder receive an alternative antibiotic. Clindamycin is not a good second choice because of the relatively high prevalence of Cutibacterium resistance to this organism. 

The authors of When intravenous vancomycin prophylaxis is needed in shoulder arthroplasty, incomplete administration is associated with increased infectious complications point out that vancomycin is often used as antimicrobial prophylaxis for shoulder arthroplasty (SA) either when cephalosporins are contraindicated or colonization with resistant bacteria is anticipated. Vancomycin is recognized as being inferior to cephalosporins in preventing Cutibacerium infections, possibly due to a higher minimum inhibitory concentration required to eradicate infection; thus, weight-based dosing is important. Vancomycin is different than most other antibiotics used in prophylaxis: it necessitates longer infusion times to mitigate potential side effects, such as Red Man Syndrome or Vancomycin flushing syndrome. When infusion is started too close to the time of the incision, administration may not be complete during surgery. 

These authors evaluated whether incomplete administration of intravenous vancomycin prior to SA affects the rate of infectious complications in primary shoulder arthroplasties (hemiarthroplasty, anatomic total SA, or reverse SA) with minimum two-year followup.

A total of 461 primary SAs were included. Vancomycin infusion was considered incomplete if the administration was not finished by 30 minutes preoperatively. (163 cases), and complete if administration was finished more than 30 minutes preoperative. (298 cases). 

The incomplete group demonstrated significantly higher rates of any infectious complication (8% vs. 2.3%); periprosthetic infection (5.5% vs. 1%), and reoperation inclusive of revision due to infectious complications (4.9% vs. 1%). 

Survivorship free of PJI was worse in SA with incomplete compared to those with complete vancomycin administration. Survival rates for incomplete and complete administration were 
97.6% and 99.3% at 1 mo, 
95.7% and 99.0% at 2 yr, 
95.1% and 99.0% at 5 yr, and 
93.9% and 99.0% at 20 yr, respectively. 

Multivariable analyses confirmed that incomplete vancomycin administration was an independent risk factor for PJI compared with complete administration (hazard ratio, 4.22), even when other independent predictors of PJI (age, male sex, prior surgery, methicillin-resistant Staphylococcus aureus colonization, and follow-up) were considered.

Comment: It is of interest that in this series from a major academic medical center, over one-third of the cases had incomplete administration of vancomycin and that those cases with incomplete administration had over 4 times the rate of infectious complications than those with complete administration. This observation suggests that it is important to obtain high blood concentrations prior to the surgical incision in order to reduce the inoculation of the wound by organisms inhabiting the dermis, such as Cutibacterium, which are not eliminated by the standard surgical skin surface preparations. The desired blood level cannot be achieved if vancomycin administration is started in the operating room because of the need for slow infusion to minimize side effects - the infusion needs to be started in the pre-operative holding area.

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III. TopIcal vancomycin

As described above, achieving high tissue levels of vancomycin with IV administration can be difficult because of the limitations on the rate of administration, because of concern about vancomycin toxicity if the weight-based dosage is exceeded, and because of the difficulties in adhering to the ideal administration timing. These concerns might be effectively addressed by the topical, rather than systemic administration of vancomycin. The authors of Vancomycin powder embedded in collagen sponge decreases the rate of prosthetic shoulder infection sought to evaluate whether Vancomycin powder embedded in a collagen sponge could decrease the rate of prosthetic shoulder infection.

They conducted a retrospective analysis of 827 patients undergoing Total Shoulder Arthroplasty (TSA) with 405 patients having no topical vancomycin and a group of 422 having the intraoperative application of intrawound vancomycin powder. Of note these two groups were not assigned randomly and the patients in each group were not systematically matched. Instead, the authors changed their protocol over the time of the study to include topical vancomycin. 

After 1 year of observation, no infections were observed in the group treated with intrawound vancomycin; 13 cases of infection (3.2%) were observed in the group without vancomycin application. No wound complications requiring revision were observed as a result of intrawound vancomycin. 

IV. Nipping it in the bud
Cutibacterium has the ability to form biofilms, especially on the titanium alloy implants from which many shoulder arthroplasty components are mode. These biofilms protect the sessile organisms from host defenses and antibiotics. Thus 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 becomes sessile in a biofilm on the implants. Vancomycin's minimum inhibitory concentration against planktonic Cutibacterium is 0.38 μg/mL while the vancomycin concentration required to eradicate an established biofilm is estimated to be ≥128 μg/mL.  A recent study showed that the concentrations of vancomycin that could be achieved in vivo were effective against planktonic Cutibacterium: In vitro susceptibility of Propionibacterium acnes [Cutibacterium] to simulated intrawound vancomycin concentrations. 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.

The authors of another study, Vancomycin is Effective in Preventing C. acnes Growth in a Shoulder Arthroplasty Mimetic found that vancomycin administration effectively prevented Cutibaterium growth in a bioartificial shoulder joint mimetic implant. 

The size of reduction in the rate of periprosthetic joint infections necessary to justify the cost of topical vancomycin was assessed in: 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.


What we know: 
1. Cutibacterium is the commonest organism to cause shoulder periprosthetic infections; the risk of these infections is increased in young male patients.
2. Cutibacterium live in the dermal pilosebaceous units of the skin overlying the shoulder where they cannot be eradicated by surgical skin surface preparations or by preoperative intravenous antibiotics
3. These dermal pilosebaceous units are incised at shoulder arthroplasty surgery, allowing planctonic Cutibaterium to contaminate the surgical field.
4. If not controlled by host defenses and prophylactic methods, these contaminating organisms can cause shoulder periprosthetic infections that are disabling for the patient and difficult to resolve once a biofilm is formed.
5. The use of topical in-wound Vancomycin appears to be safe and relatively inexpensive.
6. The clinical value of topical in-wound Vancomycin in reducing or eliminating Cutibacterium from the surgical field has yet to be rigorously demonstrated, but deserves careful study.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.

Follow on twitter: https://twitter.com/shoulderarth
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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link).



Sunday, November 13, 2022

Vancomycin prophylaxis and periprosthetic shoulder infecions.

Vancomycin is often used as antimicrobial prophylaxis for shoulder arthroplasty when first generation cephalosporins are thought to be contraindicated or colonization with resistant bacteria is anticipated. In general, vancomycin necessitates longer infusion times to mitigate potential side effects; thus logistical problems may complicate the desired completion of the infusion by 30 minutes prior to the procedure.

The authors of Intravenous Vancomycin Prophylaxis is Needed in Shoulder Arthroplasty, Incomplete Administration is Associated with Increased Infectious Complications sought to determine whether the timeliness of the administration of intravenous vancomycin prior to shoulder arthroplasty affected the rate of infectious complications.

They identified 461 primary arthroplasties performed for elective and trauma indications in which IV vancomycin was the primary antibiotic prophylaxis and 2 year followup was available.

The indication for Vancomycin was penicillin/cephalosporin allergy in 95% of the cases.

A total of 298 (64.6%) of patients received IV vancomycin at least 30 minutes before the procedure start (complete administration) and 163 (35.4%) began infusions less than 30 minutes before the procedure start (incomplete administration).


While most of the "on time" infusions took place in the preoperative holding area, all of the "late" infusions took place in the OR.




The incomplete group demonstrated higher rates of any infectious complication (8% vs. 2.3%; periprosthetic joint infectons (PJI) (5.5% vs. 1%; and reoperation inclusive of revision due to infectious complications (4.9% vs. 1%.

Survivorship free of PJI was worse in SA with incomplete compared to those with complete vancomycin administration. Of interest is that the survivorship for the incomplete infusion group continued to drop years after the procedure.

Multivariable analyses confirmed that incomplete vancomycin administration was an independent risk factor for PJI compared with complete administration (hazard ratio [HR], 4.22). Male sex (HR 4.6), MRSA colonization (HR 8.0), and followup time (HR 1.2) were also independent risk factors.


Comment: Even at the major medical center at which this study was performed, 1/3rd of the patients received "incomplete" vancomycin prophylaxis.

This paper did not present data on the causative organisms responsible for the cases of PJI; it is of interest, however, that the difference in the incidence of PJI from Cutibacterium (the most common causative organism for shoulder PJI) between the incomplete and complete vancomycin groups failed to reach statistical significance.

It is recognized that vancomycin demonstrates an inferior ability to prevent PJI when compared to cefazolin (see What antibiotic prophylaxis should be used against shoulder periprosthetic infection?)

The predominant reason for giving Vancomycin was "allergy to penicillin/cephalosporin". It is known that individuals with medical allergies have a higher rate of shoulder arthroplasty complications (see
The risk of total shoulder complications is significantly greater in patients with antibiotic allergies - why?).

Perhaps of even greater importance is that patients reporting penicillin allergy are very often not actually allergic to penicillin (see What if my total shoulder patient says she is allergic to penicillin? and When is it safe to give cephalosporin antibiotic prophylaxis to patients who are "allergic to penicillin"?

Thus while timing of Vancomycin administration may be an important factor in preventing shoulder periprosthetic infections, it may be even more important to evaluate the necessity of using Vancomycin for prophylaxis.


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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link).ore important to ascertain whether or not the patient must actually receive Vancomycin rather than the more effective cephalosporin.







Monday, September 5, 2022

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.

You can follow this blog by clicking the blue "follow" button at the upper right side of this page.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.

Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link).






Monday, May 9, 2022

What antibiotic prophylaxis should be used against shoulder periprosthetic infection?

At a recent journal club (thanks, Ben, for organizing), we discussed antibiotic prophylaxis for periprosthetic infections (PJI). It is known that multiple different organisms can cause PJI, but - especially in young healthy males - Cutibacterium is most commonly the culprit. We can provide a bit of an update on some of the key questions

(1) What is the best IV prophylactic antibiotic?

Cephalosporins seem superior as reported in Antibiotic Prophylaxis with Cefazolin Is Associated with Lower Shoulder Periprosthetic Joint Infection Rates Than Non-Cefazolin Alternatives. Among 7,713 shoulder arthroplasties 101were classified as having PJIs. Cutibacterium was identified in 44%, Staph aureus in 19%, Coagulase-negative staph in 12%, and Strep in 5%.

Cefazolin had been administered in 6,879 procedures (89.2%) and non-cefazolin antibiotics (vancomycin, clindamycin, and alternative regimens were administered in 834 procedures (10.8%). 

PJI-free survivorship was greater in shoulder arthroplasties in which cefazolin was administered compared with those in which non-cefazolin antibiotics were administered. Cefazolin administration, compared with non-cefazolin administration, was associated with a 69% reduction in all-cause PJI risk and a 78% reduction in C. acnes PJI risk. 

A higher risk of PJI for both groups was observed with vancomycin; the hazard ratio [HR] was 2.32 for all-cause PJI and 2.94 for Cutibacterium PJI. A higher risk of PJI was also observed for both groups for clindamycin; the HR was 5.07 for all-cause PJI and 8.01 for Cutibacterium PJI. The latter may be due to the pervasive use of clindamycin as a treatment for acne - a practice that may select out clindamycin resistant Cutibacterium.

It is of interest that half of the periprosthetic infections were identified more than two years after the index arthroplasty - this complicates the analysis of antibiotic efficacy in studies with only a couple of years of followup.


(2) Is Clindamycin a good alternative for patients reporting penicillin allergy?

This question was addressed in Perioperative Clindamycin Use in Penicillin Allergic Patients Is Associated With a Higher Risk of Infection After Shoulder ArthroplastyThis study reviewed seven thousand one hundred forty primary shoulder arthroplasties comparing deep surgical site infection risk in 444 patients who received perioperative vancomycin alone or 508 receiving clindamycin alone because of penicillin allergy to 6188 patients who received cefazolin alone without penicillin allergy.

Seventy deep infections were observed; most common organism was Cutibacterium acnes (39.4%). 


Compared with patients treated with cefazolin, infection risk was not different for those treated with

vancomycin, but a higher risk of infection was identified for those treated with clindamycin alone. Thus in contrast to the first study above, these authors concluded that vancomycin is preferred over clindamycin for patients with penicillin allergy. Other studies have demonstrated that patients with multiple allergies have a poorer average prognosis after arthroplasty; one might also wonder whether patients with allergies to penicillin are more susceptible to infection independent of which antibiotic is used.


(3) How can we tell if patient-reported allergy should change the antibiotic choice?

This question was addressed in A Simple Algorithmic Approach Allows the Safe Use of Cephalosporin in Penicillin-AllergicPatients without the Need for Allergy Testing. These authors point out that patients who report a penicillin allergy are often given second-line antibiotic prophylaxis during total joint arthroplasty. As seen from the article above, the use of non-cephalosporin antibiotics exposes the patient to an increased risk of PJI. These authors assessed the effectiveness of a simple penicillin allergy screening program to guide the choice of antibiotic prophylaxis.

Basically patients were grouped into three groups

 "intolerance", 


"low risk allergy"


and "high risk allergy"




The "intolerance" and " low-risk"patients received cefazolin, and the high-risk cohort received non-cefazolin antibiotics.


The protocol group (n = 2,078) was propensity score matched 1:1 with a control group that included patients who underwent TJA in the same institution prior to implementation of the protocol, the "control" group.


A total of 357 patients (17.2%) reported a penicillin allergy in the protocol group compared with 310 patients (14.9%) with a recorded allergy in the control group (p = 0.052). 


The number of patients who received non-cephalosporin antibiotics was significantly lower in the protocol group (5.7% compared with 15.2% in the control group; p < 0.001),whereas there was no difference in the rate of total allergic reactions.


Of the 239 low-risk patients (66.9%) in the protocol group, only 3 (1.3%) experienced a mild cutaneous reaction following cefazolin administration. 


There were no differences in the rates of superficial wound, deep periprosthetic, or Clostridioides difficile infections between the protocol and control groups.



(4) Is there evidence that topical Vancomycin is effective against Cutibacterium?


Vancomycin is effective in preventing Cutibacterium acnes growth in a mimetic shoulder arthroplasty


Cutibacterium loves to form biofilms on titanium alloy - one of the most common materials used in shoulder arthroplasty. We recognize that in spite of all available prophylactic measures (skin prep, IV antibiotics), arthroplasty wounds are likely to be inoculated with Cutibacterium. This is especially an issue with patients at high risk (young, healthy males, with high skin surface loads of Cutibacterium and with high serum testosterone levels) as well as those patients truly allergic to cephalosporin antibiotics.


Topical vancomycin powder is a strategy for managing Cutibacterium inoculation at the time of shoulder arthroplasty. Its efficacy is difficult to test through clinical research.


These authors investigated the efficacy of vancomycin as prophylaxis for Cutibacterium growth in vitro using a mimetic shoulder arthroplasty.


Cutibacterium strains 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. Agar plates inoculated with extracts from untreated constructs consistently resulted in the growth of large numbers of C acnes colonies


Ten milligrams of vancomycin powder was applied between the C acnes layer and the human cell–containing scaffold strips to model direct antibiotic application.

Intravenous vancomycin prophylaxis was modeled by adding vancomycin in media at 5 or 20 mg/mL. Treatments with vancomycin powder or vancomycin in media at 20-mg/mL dilution effectively prevented the recovery of any C acnes colonies. However, the lowest vancomycin dilution tested (5 mg/mL) was insufficient to prevent the recovery of C acnes colonies.


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


The authors concluded that topical vancomycin powder and high levels of vanancomycin in the media effectively prevented C acnes growth in a mimetic model of the shoulder arthroplasty environment. 


In our practice we use topical vancomycin powder in the medullary canal and in the wounds of shoulder arthroplasties, noting that the topical application avoids the risks and inconvenience of systematic vancomycin. 


You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.


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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link).


Sunday, August 15, 2021

Topical Vancomycin and periprosthetic joint infection - hip? knee? shoulder?

Can Topical Vancomycin Prevent Periprosthetic Joint Infection in Hip and Knee Arthroplasty? A Systematic Review

Using a systematic review, these authors asked: 

(1) Does topical vancomycin (vancomycin powder) reduce the risk of periprosthetic infection (PJI) in hip and knee arthroplasty? 

(2) Does topical vancomycin lead to an increased risk of complications after hip and knee arthroplasty?


They found nine eligible studies reviewing 3371 patients who received topical vancomycin (vancomycin powder) during a primary THA or TKA and 2884 patients who did not receive it.  Patients 18 years or older with a minimum follow-up of 3 months were included.  Studies were excluded if they included patients with a history of septic arthritis, used an antibiotic other than vancomycin or a different route of administration for the intervention, performed additional interventions that differed between groups, or omitted a control group. 


One of nine studies found a lower risk of PJI after primary THA or TKA, while eight did not, with odds ratios that broadly bracketed the line of no difference. 


In the six studies where overall complications could be compared between topical vancomycin and

control groups in primary THA or TKA, there was no difference in overall complication risks with vancomycin. These studies may have been underpowered to detect differences in the types of uncommon complications associated with vancomycin use (such as allergy, ototoxicity, and nephrotoxicity).


The authors point out that previous studies have sought to investigate the impact of topical vancomycin on PJI after THA and TKA with meta-analyses. In that some of these included studies that were predominantly retrospective, those of poor quality, and some that combined topical vancomycin with Betadine irrigation it has been difficult to draw meaningful conclusions regarding the effectiveness of vancomycin.


The authors of the current study restricted their inclusion criteria to patients without a history of

septic arthritis undergoing primary THA or TKA and limited the interventions to include only topical vancomycin powder administration. They found that the results of their systematic review were not sufficiently convincing on the topic of efficacy to allow them to recommend the routine use of topical vancomycin in THA and TKA.


In a discussion with the journal editor, the author of this paper stated, "While the risk of a patient experiencing a PJI is quite low, it is still a devastating complication to the patient and puts a much larger burden on the medical system. When I treat a patient with PJI, I always ask myself how we can bring the risk to 0%. We’ll never get there, but I believe it is worth exploring potential options that may further decrease the risk of PJI without increasing the risk of other complications, such as the incorporation of topical antibiotic powder. Yes, it would require quite a large sample size to detect a possible difference with the use of vancomycin powder, but our study alone is not enough to conclude whether vancomycin powder is worth using to prevent PJIs. "


Comment: In the shoulder arthroplasty world we have much less data to inform the decision to use or not use topical vancomycin in the prevention of PJI. 


What we do know is that the organism most commonly causing shoulder PJI is Cutibacterium; this is in marked contrast to the Staph, Strep and gram negative organisms that cause hip and knee PJI. Cutibacterium is an anaerobic organism that can thrive in the oxygen poor environment of the medullary canal. It is fond of forming biofilms on the titanium alloy used for most humeral components. See Shoulder joint infections and biofilms. We also know that shoulder arthroplasty incisions are routinely inoculated with Cutibacterium when the skin incision transects the dermal pilosebaceous units - especially in male patients that have high levels of Cutibacterium in their sebaceous glands. See 10 points about Cutibacterium, periprosthetic infection, and revision for failed shoulder arthroplasty


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




How you can support research in shoulder surgery Click on this link.

Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link)
How to x-ray the shoulder (see this link).
The total shoulder arthroplasty (see this link).
The ream and run technique is shown in this link.
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
Shoulder rehabilitation exercises (see this link).
Follow on twitter: Frederick Matsen (@shoulderarth)