Is skin preparation effective in reducing the incidence of Cutibacterium in shoulder arthroplasty?

The efficacy of topical preparations in reducing the incidence of Cutibacterium acnes at the start and conclusion of total shoulder arthroplasty: a randomized controlled trial

These authors investigated whether preoperative application of topical antimicrobials to the skin reduced superficial colonization and deep tissue inoculation of Cutibacterium in patients undergoing total shoulder arthroplasty who were randomized to receive either topical 

pHisoHex (hexachlorophene (n = 35), 

5% BPO (n = 33), or 

5% BPO with 1% clindamycin (n = 33). 

The initial demographics are shown here. Of note the percentage of male patients was lower for the BPO-C group than for the other groups.

Skin swabs for culture were obtained 

prior to topical application and

before surgery after topical application 

3 intraoperative swabs were obtained at surgery

dermis after incision,

on joint capsule entry, and 

dermis at wound closure

The results are shown below - the three agents performed in a similar fashion. Of note, one of the groups (BPO) differed from the other two in respect to the percentage with colonization before any treatment was applied.

These data show that Cutibacterium can persist in the dermis despite 5 applications of topical skin preparation: 22% of cases had positive dermal cultures at the beginning of the case. 

A positive Cutibacterium skin culture finding prior to surgery was predictive of intraoperative wound contamination: all 24 cases that had a positive swab culture before starting the procedure had at least one positive culture intraoperatively; in most cases, all subsequent swabs showed positive results.

Thus, failure to eradicate Cutibacterium from the skin with topical preparations consistently was associated with deep tissue inoculation.

None of the 101 control sterile swabs were culture positive for Cutibacterium.

Comment: This study demonstrated that surface washes can reduce the percent of positive skin surface cultures. There were no untreated controls, so the effect of the washes on dermal cultures at incision, joint cultures, and  dermal cultures at closure is not known. While it is recognized that young male patients are at greatest risk for Cutibacterium periprosthetic infections, the study group consisted of older patients, one third of which were female.

The authors found that all control sterile swabs were culture negative for Cutibacterium and concluded that "There is, therefore, no need for control swabs to be included in future C acnes studies".  Actually, this is not the case. As pointed out in An Evidence-Based Approach to Managing Unexpected Positive Cultures in Shoulder Arthroplasty the pooled rate of positive control cultures (sterile gauze, sterile swabs, and sterile suture) reported in the literature was 20%. Cutibacterium represented 14 (48%) of the 29 total control positives. Thus, it seems important that each investigator assess the rate of sterile control culture positivity for Cutibacterium in their environment. 

In conclusion, evidence is lacking that skin preparations can reduce the rate of positive deep wound cultures for Cutibacterium in patients known to be at high risk for Cutibacterium periprosthetic infections. In high risk patients (i.e. young male patients with high loads of Cutibacterium on their skin prior to surgery) surgeons may wish to consider the intraoperative use of Betadine washes, topical Vancomycin, and a course of postoperative oral antibiotics.

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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).

Can Benzoyl Peroxide-Miconazole Nitrate cream reduce Cutibacterium in the deep tissues of the shoulder?

 Acne Cream Reduces the Deep Cutibacterium Acnes Tissue Load before Elective Open Shoulder Surgery: A Randomized-Controlled Pilot Trial

These authors point out that Cutibacterium is the main pathogen in periprosthetic shoulder infections (PSI) and that in acne vulgaris therapy, Benzoyl Peroxide and Miconazole Nitrate cream reduces the superficial Cutibacterium burden of the skin. 

The goal of their study was to investigate the efficacy of a topical acne vulgaris cream (Benzoyl Peroxide; Miconazole Nitrate - 50 mg/g BPO and 20 mg/g MN,) in reducing subcutaneous and capsular Cutibacterium in individuals with Cutibacterium skin colonization in open shoulder surgery.

They conducted a prospective randomized pilot trial, allocating 60 adult patients (1:1) between a 7-days-preoperative application of a commercial acne cream (Benzoyl Peroxide; Miconazole Nitrate) on the preoperative skin (intervention group) versus no cream (controls). The cost of one-week therapy with the cream was about $11.

One week before surgery, and before the first application of the cream, the superficial skin over the planned shoulder incision was swabbed (sample 1) for microbiological cultures. The same skin swabbing (sample 2) was repeated in the operating room immediately before disinfection with povidone-iode, isoprophyl-alcohol and ethanol. The perioperative antibiotic prophylaxis comprised cefuroxime 1.5g intravenously tid for 24 hours. During surgery, two deep intraoperative biopsies were obtained from the subcutaneous (sample 3) and capsular tissue (sample 4).

Sixty patients (mean age 59 years, 55% females) with primary open shoulder surgery were included. 

At baseline, Cutibacterium was present on the skin in 60% (18/30 in the intervention group; 19/30 in the controls. 

In these patients with Cutibacterium skin colonization, application of acne cream resulted in an apparent reduction of the number of positive intraoperative capsular samples (0/18 vs. 4/19). However two of our statistical colleagues pointed out that this study used the Chi Square test to consider the significance of this difference of p 0.04. The Chi Square test is not appropriate with a count of 0. A Fisher's exact test is more appropriate and yields a p value of 0.105, i.e. not significant. The intervention resulted in a significant reduction of the overall number of positive intraoperative samples compared to the control group (8/18 vs. 16/19; Fishers exact p=0.02).

One patient showed an adverse reaction to the cream and was excluded from the per-protocol analysis.

It is recognized that systemic antibiotics cannot eliminate Cutibacterium from shoulder surgical wounds and carry the risk of creating resistant germs. Standard preoperative skin preparation is also ineffective in eliminating Cutibacterium from shoulder surgical wounds.

Benzoyl Peroxide (BPO) is known to have a bactericidal effect on Cutibacterium, but carries the risk of skin irritation.  Miconazole Nitrate (MN) is an imidazole derivative that interferes with lipid synthesis and membrane permeability. The author suggest that the synergistic MN favors the penetration of BPO into the bacterial cells and ultimately supports a better tolerability of the topical combination therapy. See Efficacy and tolerance of a miconazole-benzoyl peroxide cream combination versus a benzoyl peroxide gel in the topical treatment of acne vulgaris, which concluded that this combination supports a better tolerability of BPO.

Further study will be needed to clarify the value of this combination of agents in reducing the load of Cutibacterium in the deep tissues of the shoulder,

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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 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).

Does benzoyl peroxide harm the skin?

The influence of benzoyl peroxide on skin microbiota and the epidermal barrier for acne vulgaris

Benzoyl peroxide (BPO) has been advocated as a means for lowering the Cutibacterium load on the skin of patients having shoulder arthroplasty.

These authors sought to determine the effect of BPO treatment on the skin microbiome and on the epidermal barrier in 33 patients with acne vulgaris and 19 healthy controls.

All subjects received topical treatment with BPO 5% gel for 12 weeks. 

After receiving treatment with BPO, subjects had significant improvement in their Global Acne Grading System (GAGS) score, porphyrin, and red areas.

However, the epidermal barrier indices of stratum corneum hydration (SCH), and transepidermal water loss (TEWL) worsened.

When compared with baseline, microbial diversity was significantly reduced after treatment. The prevalence of the Cutibacterium was significantly reduced after treatment while the prevalence of Staphylococcus tended to increase. 

The authors concluded that BPO treatment may reduce microbial diversity and damage the epidermal barrier.

They suggested that the decline of sebum level by BPO treatment may damage the stratum corneum,

which is known to be covered with a sebum membrane and primarily composed of keratinocytes and lipids to act in the homeostatic control of water. Consequently, increased  transepidermal water loss and decreased stratum corneum hydration were observed and skin irritability and dryness occurred. 

The impaired skin barrier function could promote altered microbial colonization. Their study found that the relative abundance of Staphylococcus increased after treatment alongside a decline in SCH, deterioration of TEWL, and loss of microbial diversity. 

Comment: While BPO treatment can lessen the average load of Cutibacterium on the skin, it can also have adverse effects such as skin irritability, dryness, and cause disturbance of the microbiome (dysbiosis see Cutibacterium - friend or foe?).

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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)

Shoulder arthritis - x-ray appearance (see this link)

The smooth and move for irreparable cuff tears (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).

Safety and efficacy of benzoyl peroxide, blue light and chlorhexidine in Cutibacterium prophylaxis

 Efficacy of Combinational Therapy Using Blue Light and Benzoyl Peroxide in Reducing Cutibacterium Acnes Bioburden at the Deltopectoral Interval: A Randomized Controlled Trial

These authors compared the efficacy of blue light therapy (BLT) and 5% topical benzoyl peroxide (BPO) gel in combination with standard chlorhexidine (CHX) prep in eradicating Cutibacterium on the skin surface at the deltopectoral interval measured by positive, quantitative cultures.

Adult male volunteers were randomized to one of three treatment groups: BPO, BLT, and BPO followed by BLT. Contralateral shoulders served as matched controls. Volunteers randomized to BPO applied the gel for a total of 5 treatments. For BLT group, a single 23- minute treatment was administered at an estimated irradiance of 40 mW/cm2 (radiant exposure 55.2 J/cm2).

 For BPO+BLT group, volunteers received both treatments. After treatment with either BPO, BLT, or both, a single swab culture was taken from the skin of the treatment shoulder. Next, control and treatment shoulders were prepped with CHX, and cultures were taken from each shoulder. 

Sixty male volunteers, 20 per group. Prior to CHX administration, 56 of the 60 samples grew Cutibacterium. 

The  BPO group and BPO+BLT group had significantly less growth of Cutibacterium than the BLT group after treatment but prior to CHX. 

Following CHX administration, BPO and BPO+BLT groups had significantly fewer positive cultures  and less quantity of growth compared to their control arms. This was not seen in BLT group. 

For quantitative between group analysis, no significant synergistic effects were seen in the BPO+BLT group compared to BPO only. 

The authors concluded that blue light therapy alone did not demonstrate effective antimicrobial properties against Cutibacterium. 

Comment: 

(1) An important lesson from this study is that a substantial percentage of subjects receiving prophylaxis experienced side effects (itching, burning, dryness, peeling, flaking, erythema) that would create a concern about making a skin incision for shoulder arthroplasty through the treated area. Six out of the 20 subjects in each group reported at least 1 side effect within 1 week of treatment. These treatments may not be benign. 

(2) The skin surface cultures were obtained soon after the application of CHX. Prior studies have shown that the prophylactic effect of CHX subsides rapidly after application.

(3) This study does not examine the effectiveness of prophylaxis on the levels of Cutibacterium in the dermis. It is the dermal levels that are of concern in that the pilosebaceous units are the reservoir for Cutibacterium; the dermal incision at arthroplasty releases Cutibacterium into the wound.

See the study below:Randomized controlled trial of chlorhexidine wash versus benzoyl peroxide soap for home surgical preparation: neither is effective in removing Cutibacterium from the skin of shoulder arthroplasty patients

These authors point out that home chlorhexidine washes prior to shoulder surgery are commonly used in an attempt to reduce the skin bacterial load. However, recent studies have suggested that this agent is relatively ineffective against Cutibacterium acne.

Benzoyl peroxide (BPO) soap is a treatment for acne, but evidence regarding its effectiveness as prophylaxis in shoulder surgery is lacking. 

The objective of their study was to compare the effectiveness of home chlorhexidine washes with benzoyl peroxide soap in patients undergoing shoulder arthroplasty surgery in reducing Cutibacterium levels on the skin surface and in the dermis. 

50 male patients planning to undergo shoulder arthroplasty were consented to be randomized into treatment with 4% chlorhexidine solution (CHG) or 10% benzoyl peroxide soap (BPO) used to wash the operative shoulder the night prior and morning of surgery. 

Skin swabs prior to incision and swabs of the dermis incised after standard skin preparation and preoperative IV antibiotics were obtained, and the bacterial load was reported in a semiquantitative manner as the Specimen Cutibacterium Value (SpCuV). 

Skin surface swabs were positive in 100% of patients using CHG and 100% of patients using BPO soap. 

The Cutibacterium load (SpCuV) on the skin surface was similar between the two groups (CHG 1.6 ± 1.1 vs. BPO 1.5 ± 1.4, p = 0.681). 

The percentages of dermal cultures that were positive were not significantly different between the two groups (CHG 61% vs BPO 46%, p = 0.369). 

The Cutibacterium load (SpCuV) on the incised dermal edge was similar between the two groups (CHG 0.8 ± 1.0 vs. BPO 0.8 ± 1.4, p = 0.991). 

The authors concluded that neither BPO soap nor chlorhexidine washes prior to shoulder surgery were effective in eliminating Cutibacterium from the skin surface or the incised dermal edge. 

Follow on twitter: https://twitter.com/shoulderarth

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Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/

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)

The smooth and move for irreparable cuff tears (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).

Periprosthetic infections of the shoulder - what can be done to reduce the Cutibacterium load at the time of arthroplasty?

Cutibacterium is the pathogen most commonly isolated from periprosthetic infections of the shoulder. Because Cutibacterium is found in the dermis of normal shoulder skin, the skin incision for arthroplasty can introduce the bacteria into the shoulder wound where it can cause an infection. 

We've learned that certain patient characteristics are associated with increased risk for Cutibacterium periprosthetic infections of the shoulder, including young age, male sex, use of testosterone supplements, increased serum testosterone levels and increased loads of Cutibacterium on preoperative cultures of the unprepared shoulder skin.

We recently posted on the use of topical Betadine to reduce the load of Cutibacterium in open shoulder surgery (see this link). 

Last year a review article concluded that home skin-disinfection using benzoyl peroxide (BPO) was more effective than chlorhexidine in reducing the rate of positive Cutibacterium cultures on the skin surface but that neither completely eliminated Cutibacterium from the field (see this link).

Last month our colleagues in Linköping, Sweden published an excellent  randomized trial, Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure. They examined the effect of benzoyl peroxide (BPO) topically applied to the skin of the shoulder on bacterial colonization in 100 patients having elective shoulder surgery, randomizing the patients to preoperatively prepare their planned incisional area with either BPO or with soap (control group). 

Four skin swabs were taken in a standardized manner at different times, before and after surgical skin preparation, 1 in dermis, and finally after the skin was sutured. Before skin incision, 5 punch biopsies were retrieved spaced 2 cm apart in the planned skin incision. 

Quantification of Cutibacterium was obtained by serial dilutions.

Treatment with BPO considerably lowered the amount of Cutibacterium compared to the control group. The positive effect of BPO persisted until skin closure, at which time some recolonization of Cutibacterium had occurred.

They found that men had a 5-fold higher amount of Cutibacterium on untreated skin. 

Five patients in the study were subsequently treated for early deep surgical site infections with surgical debridement, deep tissue cultures, and antibiotics. 

Three were from the BPO group (1 woman and 2 men) and 2 men from the control group. Deep cultures from the BPO group cases detected Staphylococcus aureus in 2 and a mixture of S epidermidis and C

acnes in the third. 

Two were from the control group had a growth of Cutibacterium only.

Comment: For the shoulder surgeons and patients that have had to deal with the risk of Cutibacterium periprosthetic infections, data supporting interventions to minimize this risk are most needed and welcome. 

Evidence is mounting that  intraoperative application of Betadine is effective. Other treatments, such as topical Vancomycin and a course of post operative antibiotics are in common use, but as yet do not have rigorous data to support them. Other preventative steps include avoiding contact of implants with the cut dermal edge and handling the implant with fresh gloves. Taken together these steps are not costly in comparison to the cost and loss of comfort and function associated with a Cutibacterium infection. Even with these steps, the risk of Cutibacterium PJI cannot be completely eliminated; however, risk reduction is surely worth the effort. 

This study points to the effectiveness of the preoperative application of BPO to the skin in the area of the planned arthroplasty incision in reducing the levels of Cutibacterium in the arthroplasty wound, but that this effect is no longer significant at the time of wound closure. 

Reducing the levels of Cutibacterium  seems like a good thing, however, it is a potential concern that there were three early deep surgical site infections in the group receiving BPO and an even greater concern that three of these were infections from Staphylococcus (2 aureus and 1 epidermidis). Infections from Staphylococcus (especially aureus) are rare in the shoulder. This causes us to wonder if Cutibacterium is more Jekyll or Hyde (see this link). It would be unfortunate to lower the risk of Cutibacterium while increasing the rate of Staph.

We can be sure to learn more from future clinical research on this critical topic.

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).

The smooth and move procedure for irreparable rotator cuff tears (see this link).

Shoulder rehabilitation exercises (see this link).

Follow on twitter: Frederick Matsen (@shoulderarth)

Benzoyl peroxide treatment: what is its effect on Cutibactacterium on and in the skin?

Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure

These authors point out that most of the surgical site infections after shoulder surgery are caused by Cutibacterium. Topically applied benzoyl peroxide (BPO) has for years been used to decrease the skin load of Cutibacterium in treatment of acne vulgaris. They examined this effect on bacterial colonization in patients subjected to elective shoulder surgery at different stages of the procedure in 100 patients scheduled for primary elective open shoulder surgery. Patients were randomized to preoperative skin preparation either with BPO or with soap (control group). 

All patients were instructed to shower and wash with regular soap the night before and in the morning of the day of surgery. The BPO group were instructed as follows: in the morning and evening two days prior to surgery a 5 cm strip of 5% BPO gel was applied to the shoulder on dry skin and rubbed in. The procedure was repeated next day and a fifth and final application was made in the morning on the day of surgery. The last two applications were made after showering. 

Four skin swabs were taken in a standardized manner at different times, before and after surgical skin preparation, one in dermis, and finally after the skin was sutured. Before skin incision five punch biopsies (3 mm in diameter and maximum 4 mm deep) were obtained spaced 2 cm apart in the planned skin incision. 

They found that men had a five-fold higher amount (colony forming units/ml) of Cutibacterium on untreated skin. Treatment with BPO considerably lowered this count compared to the control group. This positive effect of BPO persisted until skin closure, a point at which some recolonization of Cutibacterium occurred; recolonization was to a higher degree in the control group. No patients were noted to have side effects from the skin preparation.

Dermal skin swabs showed bacterial growth in 31/100 participants. There was mixed bacterial flora in 3/31: two with S. saprophyticus and in one S. epidermidis. In the remaining 28/31 there was growth solely of Cutibacterium– 17/55 in the control group and 11/45 in the BPO group. Only 12 of these had bacterial growth when culturing the biopsies. Bacterial counts in the dermis showed no difference between the groups.

23/100 patients had bacterial growth in the biopsies, 15 men and 2 women in the control group (n=55) and 6 men and no woman in the BPO group (n=45). Out of these 23, there was Staphylococci growth in five (4/5 control group, 1/5 BPO group). Remaining 18/23 had Cutibacterium but not in all biopsies. There was no significant difference between the groups when requiring three out of five as a positive culture.

Comment: This is a well done, controlled study. It is of interest that BPO appeared to have an effect on the skin surface swabs, but not on the dermal samples (swabs or punch biopsies). 12 of subjects with the culture negative swabs after skin preparation still had viable bacteria in the dermal cultures. Thus despite preoperative skin preparation, viable Cutibacterium persisted in the dermal layer. 

It seems likely that these living bacteria in the dermal layer are released into the surgical field when the surgeon cuts through the skin

The reader interested in the value of benzoyl peroxide skin treatment will want to read these six posts:

link1, link2, link3, link4, link5, link 6

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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 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).

Home Prophylaxis with Benzoyl Peroxide or Chlorhexidine in Shoulder Surgery

 Efficacy of Home Prophylactic Benzoyl Peroxide and Chlorhexidine in Shoulder Surgery.A Systematic Review and Meta-Analysis

Articles were included in this review if they (1) had a clear objective of investigating the effectiveness of a home prophylactic measure prior to shoulder surgery, (2) reported a primary outcome of skin surface culture positivity or diagnosis of infection with Cutibacterium, and (3) were in the English language.

Chlorhexidine can be administered in a variety of formulations, including infused cloths or a topical solution with concentrations ranging from 2% to 4%. On the other hand, BPO can be administered as a 5% gel or applied as an emollient foam. In each of the evaluated studies, BPO was consistently applied preoperatively in gel form.

Chlorhexidine, with or without isopropyl alcohol, is a broad-spectrum antiseptic effective against most grampositive and gram-negative bacteria and fungi and exhibits both bacteriostatic and bactericidal activity.

BPO functions as an antimicrobial agent that is toxic to ductal bacteria because its lipophilic structure allows it to penetrate into the pilosebaceous glands. Once it has entered, it decomposes to release free radicals to eradicate bacteria in sebaceous follicles. 

BPO treatment resulted in a significantly lower rate of culture positivity (17%) compared with chlorhexidine treatment (37%, p , 0.00001).

As none of the studies reported infections, the authors could not compare the effectiveness of the preparations in reducing infection rates. There were insufficient data available to compare adverse reactions from the use of BPO and Chlorhexidine.

Comment: This is an important area of study, in that Cutibacterium periprosthetic infections (PJI) are a major issue in shoulder arthroplasty. Young male patients are known to be at increased risk. Thus it would be of interest to see a comparison of these two preparations in that higher risk population. Currently, it is possible to assess the load of bacteria culture specimens, so it would be of interest to know the effect of these two agents on the amount of bacteria in the specimen (not just the presence or absence). 

Finally, it is of interest that neither agent was completely successful in eliminating Cutibacterium from the skin cultures. This points to the fact that a multimodal approach to reducing the chance of Cutibacterium PJI is needed - especially in patients at high risk - including preoperative skin treatment, intraoperative measures (e.g. irrigation, Betadine lavage, topical antibiotics, etc), and consideration of a short course of postoperative antibiotics.

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