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Int Orthop. Author manuscript; available in PMC 2024 Jun 1.
Published in final edited form as:
Int Orthop. 2023 Jun; 47(6): 1511–1515.
Published online 2023 Mar 29. doi:10.1007/s00264-023-05786-x
PMCID: PMC10694997
NIHMSID: NIHMS1946545
PMID: 36977799
Jason E. Hsu, M.D.,1 Anastasia J. Whitson, BSPH,1 Rufus Van Dyke, M.D.,1 John C. Wu, M.D.,1 Frederick A. Matsen, III, M.D.,1 and Dustin R. Long, M.D.2
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Abstract
Purpose:
The objective of this study was to characterize the temporal dynamics of Cutibacterium repopulation of the skin surface after application of chlorhexidine to the shoulder.
Methods:
Ten shoulders in 5 male subjects were used. A skin swab was taken prior to (0 minutes) and then at 3, 30, 60, 120, and 240 minutes after skin preparation with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Semi-quantitative bacterial load was measured for each timepoint.
Results:
From 0 minutes (pre-treatment) to 3 minutes, chlorhexidine-isopropyl alcohol reduced the skin bacterial load in 8 out of 10 shoulders. Of these 8 shoulders, 4 (50%) had growth by 30 minutes, 7 (88%) had growth by 60 minutes, and all 8 (100%) had growth by 240 minutes. Compared to the 3 minutes after chlorhexidine application, bacterial load had significantly increased by 60 minutes but were still significantly lower than the pre-prep bacterial load (0 minutes).
Conclusion:
Following standard surgical skin preparation with chlorhexidine-isopropyl alcohol, the surface of the shoulder is repopulated with Cutibacterium within one hour, presumably from reservoirs in sebaceous glands not penetrated by topical antiseptic agents. Since these dermal glands are transected by skin incision for shoulder arthroplasty, this study suggests that they may be sources of wound contamination during surgery in spite of skin preparation with chlorhexidine.
Level of Evidence:
laboratory study
Keywords: shoulder PJI, antiseptic, chlorhexidine, Cutibacterium, skin
INTRODUCTION
Skin antisepsis prior to shoulder surgery is aimed at minimizing the risk of bacterial inoculation of the deeper tissues and onto prosthetic components once skin incision is made. The most common bacterium causing shoulder periprosthetic joint infection (PJI) is Cutibacterium acnes [9, 17]. This bacterium has the unique property of feeding off fatty acids in the sebaceous glands common around the shoulder and living in the relatively anaerobic environment beneath the skin surface. Because of the ability of Cutibacterium to exist under the skin surface, antiseptic approaches must account for the fact that agents applied to the surface may not eliminate bacteria in the subepidermal layers that are transected in surgical procedures on the shoulder.
Chlorhexidine gluconate is a commonly utilized skin preparation in orthopaedic surgery and is recommended as the standard skin preparation solution prior to shoulder arthroplasty [6]. However, more recently, its effectiveness in shoulder surgery has been questioned. Studies have demonstrated that standard skin antiseptics may not significantly decrease the load of Cutibacterium on the skin surface [11, 16, 21]. In addition, there are concerns that the inability of standard antiseptics to reach the pilosebaceous glands where Cutibacterium reside can lead to persistence of the bacterium in the dermal structures that are exposed at the time of surgery [5].
The time course of the response of skin surface Cutibacterium loads to chlorhexidine application have not been well-described. Therefore, the objective of this study was to characterize the temporal dynamics of skin surface repopulation of Cutibacterium onto the skin surface after application of standard chlorhexidine antiseptic.
METHODS
Participants
Ten shoulders in 5 consenting male volunteers were included in this study. We enrolled male subjects only, given the clear data showing the risk for positive skin surface cultures and deep cultures is significantly higher in men [5, 10, 19]. Mean age of the participants was 38 years (range, 32-51). Participants had no history of prior surgery and did not have any history of antibiotic use within the preceding 3 months.
Skin sampling and culturing protocol
A standard clinical swab (ESwab #480C, Copan Diagnostics, Inc., Murrieta, CA, USA) was used to collect skin surface samples as previously described [10]. Pen-like pressure was used to swab a line 2 cm in length over the coracoid process. The swab was turned 90 degrees and swabbed an additional 3 times. The swab was then sent within one hour to the lab for culturing on multiple media types and held for 21 days as previously described [3, 15].
Skin sampling was performed immediately prior to antiseptic treatment (0 minutes) as a baseline. This time point was defined as the “pre-prep baseline.” A 2% chlorhexidine gluconate (CHG) and 70% isopropyl alcohol (IPA) skin preparation solution (ChloraPrep, BD, Franklin Lakes, NJ) was applied over the area of a typical deltopectoral incision following the manufacturer’s directions. This was followed by a 3-minute drying period as recommended by the manufacturer. Subsequent skin sampling was performed at 3 minutes, 30 minutes, 60 minutes, 120 minutes, and 240 minutes to assess bacterial load on the skin after application. Between each time point, a sterile surgical dressing was applied over the sampling area to prevent exogenous contamination. Skin samples taken at 3 minutes (first sample after preparation) were defined as the “post-prep baseline.” Two shoulders in which there was no decrease from 0 minutes (pre-prep baseline) to 3 minutes (post-prep baseline) were excluded from the temporal analysis and of the surface bacterial load as measurement of repopulation dynamics was not possible for cases without initial response to treatment.
Reporting of semi-quantitative culture results
Bacterial load was reported in a semi-quantitative manner as the Specimen Cutibacterium Value (SpCuV) scale where no growth is assigned a value of 0, one colony or broth only growth is assigned a value of 0.1, then 1+, 2+, 3+, and 4+ growth assigned values of 1, 2, 3, and 4, respectively [1].
Statistical analysis
Repopulation growth curves were constructed by calculating the proportion with positive cultures (SpCuV >0) over time. SpCuV was treated as an ordinal variable. A Mann-Whitney U test was used to compare time points.
RESULTS
Skin surface preparation with chlorhexidine-isopropyl alcohol was initially effective in decreasing the SpCuV from 0 minutes (pre-prep) to 3 minutes (post-prep) in 8 out of 10 shoulders (80%). At each subsequent time point, the proportion of samples with increased growth compared with the post-prep baseline was increased (50% at 30 minutes, 88% at 60 and 120, 100% at 240 minutes; Figure 1).
Figure 1:
Proportion of patients with a higher Specimen Cutibacterium Value (SpCuV) at 30, 60, 120, and 240 minutes compared to post-preparation baseline (3 minutes).
For the 8 shoulders initially responding to Chlorhexidine, the mean skin SpCuV was significantly decreased from 2.4 at 0 minutes to 0.1 immediately after skin prep (3 minutes). At each subsequent time point, the bacterial load increased from a mean of 0.63 at 30 minutes (p=0.208) to 1.1 at 60 minutes (p=0.010) to 1.4 at 120 (p=0.009) and 240 minutes (p=0.002) (Figure 2). While all 8 of the shoulders showed cutibacterium growth at 240 minutes, the mean SpCuV of 1.4 remained significantly lower than the mean pre-prep baseline of 2.4 (p=0.024).
Figure 2:
Skin surface Cutibacterium load recovery after chlorhexidine preparation. * p<0.05. SpCuV, Specimen Cutibacterium Value.
DISCUSSION
Cutibacterium can exist in both aerobic and anaerobic environments and can feed off fatty acids contained with pilosebaceous glands. Given the location of these glands beneath the skin surface, it may be difficult for skin surface preparations to eradicate bacteria from the deeper dermal layers which are incised at surgery. This study demonstrates that, following standard surgical preparation with chlorhexidine, repopulation of the skin surface by Cutibacterium occurs over one hour. These organisms likely arise from Cutibacterium reservoirs in sebaceous glands which repopulate the epidermis as sebum flows to the skin surface (Figure 3). These findings emphasize the need for alternative skin prophylactic measures or intraoperative treatments specifically targeting bacteria in the subepidermal skin structures.
Figure 3:
A) At 0 minutes (pre-prep), Cutibacteria (represented by red dots) is present on the skin surface and the pilosebaceous glands. (B) At 3 minutes (post-prep), the Cutibacteria on the surface of the skin has been eliminated by the skin preparation, but the Cutibacteria in the pilosebaceous glands remain. (C) By 60 minutes post-prep, the Cutibacteria from the pilosebaceous glands repopulates the skin surface. Modified from the National Institutes of Health (NIH), Department of Health and Human Services.
Several adjuvant skin preparations to chlorhexidine have been investigated in shoulder surgery [18]. Benzoyl peroxide can be applied by the patient at home in the days prior to shoulder surgery. Studies have suggested that this approach can decrease, but not completely eliminate, the bacterial burden of Cutibacterium on the skin [13, 18, 20, 22]. Hydrogen peroxide applied to the skin surface just prior to skin incision has also been suggested as an adjunctive prophylactic measure. While two studies suggest a decrease in the rate of positivity of deeper cultures taken after skin incision [4, 23], another randomized controlled trial has suggested a lack of efficacy[7] and the clinical efficacy of these measures for the outcome of prosthetic joint infection has not been studied.
A number of studies have utilized skin biopsy samples to access the deeper dermal structures including pilosebaceous glands [8, 14]. While this method does allow for sampling of the pilosebaceous glands, it is relatively invasive and often requires local anesthetic such as lidocaine in the area of the biopsy which may affect culture results given the potential cytotoxic nature of some local anesthetics [2, 12]. Because skin surface levels of Cutibacterium emanate from the dermal glands, these skin surface levels provide an indication of the effectiveness of different approaches to prophylaxis. The results of this study suggest that skin surface preparation with chlorhexidine initially substantially reduces the skin levels of Cutibacterium but that much of this effectiveness is lost after 60 minutes.
This study has a few limitations. First, given the invasiveness of dermal punch biopsies, we decided against its utilization as a comparator in this study. As a result, association between repopulation of Cutibacterium onto the skin surface from the sebaceous glands after skin preparation is likely but not proven. Second, we utilized both shoulders from 5 volunteers. Results may have been different if one shoulder from 10 separate volunteers were tested. Third, we used male volunteers only due to the higher risk for periprosthetic infection; therefore, our results may not be applicable to all patients.
In conclusion, following standard surgical preparation of the shoulder with chlorhexidine-isopropyl alcohol, Cutibacterium largely repopulates the skin surface within an hour, presumably from reservoirs in sebaceous glands not penetrated by topical antiseptic agents. Since these dermal glands are transected by the skin incision for shoulder arthroplasty, this study suggests that they may be sources of wound contamination during surgery in spite of the skin preparation with chlorhexidine.
Acknowledgements:
The authors acknowledge support for this study from the University of Washington’s Douglas T. Harryman II/Depuy Endowed Chair for Shoulder Research and The Rick and Anne Matsen Endowed Professorship for Shoulder Research.
We would also like to thank Susan DeBartolo (University of Washington, Department of Orthopaedics and Sports Medicine) for her editorial work on the manuscript.
Funding:
Dr. Long reports his efforts on this project were supported by the following National Institutes of Health awards: National Institute of General Medical Sciences T32 GM086270-11 and National Institute of Arthritis and Musculoskeletal and Skin Diseases 1K23AR080209-01.
Relevant financial activities outside of the submitted work for Dr. Hsu: Consultation/personal fees for DJO Surgical, committee member of the American Shoulder and Elbow Surgeons, and Associate Editor for the Journal of Bone and Joint Surgery.
Footnotes
Competing Interests:
Authors Anastasia Whitson and Drs. Van Dyke, Wu, and Matsen declare they have no financial interests. Dr. Jason Hsu reports the relevant financial activities outside of the submitted work: Consultation/personal fees for DJO Surgical, committee member of the American Shoulder and Elbow Surgeons, and Associate Editor for the Journal of Bone and Joint Surgery.
Ethical Approval/IRB: Not applicable.
Consent to Participate: Informed consent was obtained from all patients included in this study.
Consent to Publish: Non applicable.
Code availability: N/A.
Informed consent: Formal consent was obtained from all patients included in this study.
Availability of data and material:
Data has not been deposited into a public repository but is available upon request.
REFERENCES
1. Ahsan ZS, Somerson JS, Matsen FA 3rd (2017) Characterizing the propionibacterium load in revision shoulder arthroplasty a study of 137 culture-positive cases. J Bone Joint Surg Am99:150–154. doi: 10.2106/JBJS.16.00422 [PubMed] [CrossRef] [Google Scholar]
2. Aydin ON, Eyigor M, Aydin N (2001) Antimicrobial activity of ropivacaine and other local anaesthetics. Eur J Anaesthesiol18:687–694. doi: 10.1046/j.1365-2346.2001.00900.x [PubMed] [CrossRef] [Google Scholar]
3. Butler-Wu S, Burns EM, Pottinger PS, Magaret AS, Rakeman JL, Matsen FA 3rd, Cookson BT (2011) Optimization of periprosthetic culture for diagnosis of Propionibacterium acnes prosthetic joint infection. J Clin Microbiol49:2490–2495. doi: 10.1128/JCM.00450-11 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
4. Chalmers PN, Beck L, Stertz I, Tashjian RZ (2019) Hydrogen peroxide skin preparation reduces Cutibacterium acnes in shoulder arthroplasty: a prospective, blinded, controlled trial. J Shoulder Elbow Surg28:1554–1561. doi: 10.1016/j.jse.2019.03.038 [PubMed] [CrossRef] [Google Scholar]
5. Falconer TM, Baba M, Kruse LM, Dorrestijn O, Donaldson MJ, Smith MM, Figtree MC, Hudson BJ, Cass B, Young AA (2016) Contamination of the surgical field with Propionibacterium acnes in primary shoulder arthroplasty. J Bone Joint Surg Am98:1722–1728. doi: 10.2106/JBJS.15.01133 [PubMed] [CrossRef] [Google Scholar]
6. Garrigues GE, Zmistowski B, Cooper A, Green A, ICM Shoulder Group (2019) Proceedings from the 2018 International Consensus Meeting on Orthopedic Infections: the definition of periprosthetic shoulder infection. J Shoulder Elbow Surg28:S8–S12. doi: 10.1016/j.jse.2019.04.034 [PubMed] [CrossRef] [Google Scholar]
7. Grewal G, Polisetty T, Boltuch A, Colley R, Tapia R, Levy JC (2021) Does application of Hydrogen Peroxide to the dermis reduce incidence of Cutibacterium acnes during shoulder arthroplasty: a randomized control trial. J Shoulder Elbow Surg30:1827–1833. doi: 10.1016/j.jse.2021.03.144 [PubMed] [CrossRef] [Google Scholar]
8. Heckmann N, Sivasundaram L, Heidari KS, Weber AE, Mayer EN, Omid R, Vangsness CT Jr., Hatch GF 3rd (2018) Propionibacterium acnes persists despite various skin preparation techniques. Arthroscopy34:1786–1789. doi: 10.1016/j.arthro.2018.01.01 [PubMed] [CrossRef] [Google Scholar]
9. Hsu JE, Bumgarner RE, Matsen FA 3rd (2016) Propionibacterium in shoulder arthroplasty: what we think we know today. J Bone Joint Surg Am98:597–606. doi: 10.2106/JBJS.15.00568 [PubMed] [CrossRef] [Google Scholar]
10. Hsu JE, Neradilek MB, Russ SM, Matsen FA 3rd (2018) Preoperative skin cultures are predictive of Propionibacterium load in deep cultures obtained at revision shoulder arthroplasty. J Shoulder Elbow Surg27:765–770. doi: 10.1016/j.jse.2018.01.021 [PubMed] [CrossRef] [Google Scholar]
11. Hsu JE, Whitson AJ, Woodhead BM, Napierala MA, Gong D, Matsen FA 3rd (2020) 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. Int Orthop44:1325–1329. doi: 10.1007/s00264-020-04594-x [PubMed] [CrossRef] [Google Scholar]
12. Johnson SM, Saint John BE, Dine AP (2008) Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt)9:205–213. doi: 0.1089/sur.2007.036 [PubMed] [Google Scholar]
13. Kolakowski L, Lai JK, Duvall GT, Jauregui JJ, Dubina AG, Jones DL, Williams KM, Hasan SA, Henn RF 3rd, Gilotra MN (2018) Neer Award 2018: Benzoyl peroxide effectively decreases preoperative Cutibacterium acnes shoulder burden: a prospective randomized controlled trial. J Shoulder Elbow Surg27:1539–1544. doi: 10.1016/j.jse.2018.06.012 [PubMed] [CrossRef] [Google Scholar]
14. Lee MJ, Pottinger PS, Butler-Wu S, Bumgarner RE, Russ SM, Matsen FA 3rd (2014) Propionibacterium persists in the skin despite standard surgical preparation. J Bone Joint Surg Am96:1447–1450. doi: 10.2106/JBJS.M.01474 [PubMed] [CrossRef] [Google Scholar]
15. Matsen FA 3rd, Butler-Wu S, Carofino Bc, Jette JL, Bertelsen A, Bumgarner RE (2013) Origin of propionibacterium in surgical wounds and evidence-based approach for culturing propionibacterium from surgical sites. J Bone Joint Surg Am95:e1811–1817. doi: 10.2106/JBJS.L.01733 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
16. Matsen FA 3rd, Whitson AJ, Hsu JE (2020) While home chlorhexidine washes prior to shoulder surgery lower skin loads of most bacteria, they are not effective against Cutibacterium (Propionibacterium). Int Orthop44:531–534. doi: 10.1007/s00264-019-04477-w [PubMed] [CrossRef] [Google Scholar]
17. Nelson GN, Davis DE, Namdari S (2016) Outcomes in the treatment of periprosthetic joint infection after shoulder arthroplasty: a systematic review. J Shoulder Elbow Surg25:1337–1345. doi: 10.1016/j.jse.2015.11.064 [PubMed] [CrossRef] [Google Scholar]
18. Nhan DT, Woodhead BM, Gilotra MN, Matsen FA 3rd, Hsu JE (2020) Efficacy of home Prophylactic Benzoyl Peroxide and Chlorhexidine in shoulder surgery: a systematic review and meta-Analysis. JBJS Rev8:e2000023. doi: 10.2106/JBJS.RVW.20.00023 [PubMed] [CrossRef] [Google Scholar]
19. Richards J, Inacio MCS, Beckett M, Navarro RA, Singh A, Dillon MT, Sodl JF, Yian EH (2014) Patient and procedure-specific risk factors for deep infection after primary shoulder arthroplasty. Clin Orthop Relat Res472:2809–2815. doi: 10.1007/s11999-014-3696-5 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
20. Sabetta JR, Rana VP, Vadasdi KB, Greene RT, Cunningham JG, Miller SR, Sethi PM (2015) Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoulder surgery. J Shoulder Elbow Surg24:995–1004. doi: 10.1016/j.jse.2015.04.003 [PubMed] [CrossRef] [Google Scholar]
21. Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL (2009) Efficacy of surgical preparation solutions in shoulder surgery. J Bone Joint Surg Am91:1949–1953. doi: 10.2106/JBJS.H.00768 [PubMed] [CrossRef] [Google Scholar]
22. Scheer V, Jungestrom MB, Lerm M, Serrander L, Kalen A (2018) Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes: a randomized study. J Shoulder Elbow Surg27:957–961. doi: 10.1016/j.jse.2018.02.038 [PubMed] [CrossRef] [Google Scholar]
23. Stull JD, Nicholson TA, Davis DE, Namdari S (2020) Addition of 3% hydrogen peroxide to standard skin preparation reduces Cutibacterium acnes-positive culture rate in shoulder surgery: a prospective randomized controlled trial. J Shoulder Elbow Surg29:212–216. doi: 10.1016/j.jse.2019.09.038 [PubMed] [CrossRef] [Google Scholar]
