- Email: [email protected]
The Diagnosis and Management of Periprosthetic Joint Infections of the Shoulder
The Diagnosis and Management of Periprosthetic Joint Infections of the Shoulder Jia-Wei Kevin Ko, MD,* and Surena Namdari, MD, MSc† Periprosthetic joint infection of the shoulder is a rare complication of shoulder arthroplasty, which can have a profound effect on a patient's clinical outcome and function. The diagnosis and management of these infections is challenging, largely because of the unique microbiome of the shoulder. As current treatment strategies are based upon the infection literature in hip and knee arthroplasty, there is little evidence to support their effectiveness in the shoulder. Although there continues to be innovations in the diagnosis and treatment of this unique joint infection, improving the understanding of periprosthetic joint infection of the shoulder remains an active area of research. Oper Tech Orthop ]:]]]-]]] C 2016 Elsevier Inc. All rights reserved.
KEYWORDS periprosthetic infection, shoulder arthroplasty, complications
Introduction
P
eriprosthetic joint infections (PJIs) of the shoulder are a relatively uncommon complication of shoulder arthroplasty with studies suggesting a rate between 0.7% and 1.8% in primary shoulder arthroplasty and up to 15.4% in revision arthroplasty.1-7 National rates of PJI involving the shoulder have remained relatively constant over the past decade, suggesting that surgeons are not much better at preventing them, and that the number of infections encountered would mirror the increase in shoulder arthroplasty utilization.6 Projections suggest that 46000 new shoulder PJI cases would be encountered each year in the most conservative of estimates.6,8 Although much of our historical understanding of the diagnosis and management of shoulder PJI has been extrapolated from the literature on hip and knee PJI, it is now understood that the unique microbiome of the shoulder may make correlations between lower extremity PJI and shoulder
*Orthopedic Physician Associates at Swedish Orthopedic Institute, Seattle, WA. †The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA. *Address reprint requests to Surena Namdari, MD, MSc, The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA E-mail: [email protected]
http://dx.doi.org/10.1053/j.oto.2015.12.001 1048-6666//& 2016 Elsevier Inc. All rights reserved.
PJI inaccurate. It is becoming increasingly recognized that lowvirulence organisms such as Propionibacterium acnes (P. acnes) and coagulase-negative Staphylococcus species play a more prominent role in PJI involving the shoulder.3,9 This not only underscores the diagnostic challenge of identifying these organisms, but also suggests that the historic rates of shoulder PJI likely underestimate the true incidence of this challenging problem. As our diagnostic tools improve and evolve, it now seems that the harder we search for shoulder PJI, the more likely we are to find it. The goal of this article would be to summarize our current understanding of the diagnosis and management of shoulder PJI through an evidence-based approach.
Clinical Evaluation It is nearly impossible to completely rule out the possibility of infection in any patient who presents to the hospital with a painful or poorly functioning shoulder arthroplasty with current diagnostic tools. Because of this, the highest index of suspicion must be maintained through all steps of the diagnostic workup and any revision procedures undertaken. It is important to remember that, even in the face of obvious mechanical or soft tissue failure, there may be concomitant infection present within the shoulder. One of the reasons for this vigilance is that we now understand that the usual sterile 1
J.-W.K. Ko and S. Namdari
2 preparation of the shoulder is not sufficient to eliminate P. acnes that densely populates the sebaceous glands within the dermal layer of the shoulder.10 Therefore, it is safe to assume that every surgical wound about the shoulder has the potential to contaminate the deep underlying tissues, and studies have suggested that this is likely the case.11-13 The identified risk factors for developing a PJI of the shoulder include male sex,4,14 younger age,4 posttraumatic arthroplasty,15 and the presence of a postoperative hematoma.16 Owing to the higher bacterial prevalence within hair follicles and pores, P. acnes is more commonly associated with men. A possible explanation for the decrease in infection risk with age may relate to the decrease in sebaceous gland secretion with age, resulting from the concomitant decrease in the endogenous production of androgens.17,18 Additionally, infection may be more common following reverse total shoulder arthroplasty19 and revision surgery.20 Other comorbid conditions such as obesity, diabetes, smoking, malnutrition, chronic kidney or liver disease, and immunosuppression have yet to be identified as risk factors, although this is likely because of the fact that most of the current studies have been underpowered to detect a difference in these parameters. Clinical signs and symptoms can vary and are often nonspecific. Although overt signs of infection, such as fevers, chills, erythema, swelling, or a draining sinuse, are easy to identify, they typically only occur with more virulent organisms.5 Some of the most common symptoms, including pain and stiffness, are ubiquitous in nearly all poorly functioning shoulder arthroplasties, but are often the only signs present with low-virulence organisms such as P. acnes.14 A thorough clinical history should be elicited,
A
noting any postoperative wound-healing issues, superficial wound infections, and potential sources for hematogenous seeding of the shoulder joint.
Diagnostic Evaluation Radiologic Evaluation The diagnostic evaluation of a potentially infected shoulder arthroplasty typically starts with radiographs. Radiographs allow for the initial evaluation of other potential causes of a failed shoulder arthroplasty and may demonstrate hallmark findings of infected arthroplasty. Although radiographs cannot confirm an infection, humeral osteolysis, and component loosening have been associated with PJI in the shoulder14 (Fig. 1). More suppurative infections may also demonstrate joint effusion, periosteal reaction, or endosteal scalloping on radiographs. The 3-dimensional imaging including computed tomography scans and magnetic resonance imaging of the shoulder is not typically helpful in the diagnosis of shoulder PJI. Largely, this is because the existing implant can create a substantial amount of artifact on advanced imaging, making interpretation of the study very difficult. However, with metal suppression techniques, these studies are often ordered, more for the purpose of determining rotator cuff integrity and bone loss for preoperative planning, than as a diagnostic tool for shoulder PJI. Radionuclide imaging has not been well studied as a diagnostic tool for identifying infection in shoulder arthroplasty. A labeled white blood cell (leukocyte) imaging study
B
Figure 1 Sequential radiographs of an infected total shoulder arthroplasty, which demonstrate progressive humeral osteolysis most prominent in the inferomedial calcar (A) at 6 years and (B) at 7 years.
The diagnosis and management of PJIs of the shoulder holds the most promise as other radionuclide studies would not differentiate between septic and aseptic loosening. The role of radionuclide imaging in the lower extremity PJI has been studied with unknown benefit.21 Based on the current literature, it is impossible to recommend for or against radionuclide imaging in the diagnosis of shoulder PJI.
Serologic Evaluation Serologic testing is a standard part of the evaluation of any potential PJI. Acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can be elevated in the face of infection, but are nonspecific for infection and can be elevated with any ongoing inflammatory process. More importantly, they are often normal with the lowgrade infections that commonly afflict the shoulder.3,22,23 In a series of 107 patients with unexpected positive intraoperative cultures, Foruria et al24 reported that the ESR was positive in only 5% and the CRP was positive in only 12%. This is in contrast to PJI of the hip and knee where inflammatory markers have a relatively high-negative predictive value and are one of the key diagnostic tests.25,26 Owing to the poor diagnostic accuracy of ESR and CRP, interleukin-6 (IL-6) is a proinflammatory cytokine, which has also been evaluated for identifying shoulder PJI. IL-6 has been used both as a serologic test and as a synovial fluid test, the latter of which would be discussed in a separate section. As a serologic test, IL-6 has shown promise for use in hip and knee PJI.27 However, much like the use of ESR and CRP, the same promise has not been realized in shoulder PJI. Studies have demonstrated the poor sensitivity of serum IL-6 in infected shoulder arthroplasty, making it of limited utility as a diagnostic test.28,29
Synovial Fluid Evaluation The utility of a shoulder aspiration to evaluate for shoulder PJI remains a subject of debate. Although aspiration is a relatively low-risk procedure that can sometimes be performed in the office setting with or without imaging guidance, it can often be difficult to obtain enough fluid for analysis. Recommendations from the hip and knee PJI literature suggest that aspirations should be performed if there are elevated inflammatory markers.30 However, we know that ESR and CRP are often normal in the setting of shoulder PJI. Additionally, infections with low-virulence organisms do not necessarily generate much of a host reaction or enough excess synovial fluid to be easily obtained. There also remains the hypothetical risk for seeding a noninfected joint or falsepositive result through P. acnes contamination with a needle puncturing an underlying sebaceous gland. Until the role of aspiration is more clearly defined in the literature, whether or not to perform an aspiration remains the preference of the treating surgeon. If an aspiration is successful in obtaining enough fluid for analysis, the fluid should be sent for synovial leukocyte count, cell differential, and culture, at a minimum.
3 Synovial Leukocyte Count In the hip and knee literature, a threshold of 1700 cells/μL with 460% polymorphonuclear (PMN) cells has been suggested as a cutoff for being highly suspicious for infection.31 In the absence of studies looking specifically at thresholds in shoulder PJI, these numbers serve as a rough guideline for synovial fluid analysis in the prosthetic shoulder as well. However, it is likely that thresholds in the hip and knee are different from thresholds in the shoulder, particularly with the higher prevalence of low-virulence organisms. With this in mind, a significantly elevated synovial leukocyte count may be diagnostic for infection; however, a low or “normal” synovial leukocyte count cannot definitely rule out the presence of infection. Culture Synovial fluid should also be sent for aerobic and anaerobic cultures. It is important to request that the laboratory hold the cultures for a minimum of 14 days in an effort to isolate fastidious organisms such as P. acnes. In the knee literature, it is known that the false-negative culture rates can be as high as 34% of cultures from preoperative aspiration.32 The sensitivity and specificity of cultures from preoperative shoulder aspirates has not been studied; however, given the relatively low sensitivity from the available total joint literature, a negative culture cannot definitively rule out the presence of infection. Rather, cultures can only be used to increase the suspicion for true infection. Diagnostic Arthroscopy A method for evaluating a potentially infected shoulder arthroplasty is use of diagnostic arthroscopy. This method has the advantage of being able to obtain tissue cultures from the shoulder joint, which has been shown to more reliable than preoperative aspiration results.33,34 Additionally, this approach allows the opportunity to assess for other causes of a painful shoulder arthroplasty, including glenoid loosening or rotator cuff failure (Fig. 2). A diagnostic arthroscopy avoids the morbidity of an open surgery; however, if an infection is discovered, a secondary procedure may be needed. We reserve this approach for patients where other diagnostic tests have not given a clear reason for failure or poor function.
Figure 2 Arthroscopic image of a loose glenoid in an infected shoulder arthroplasty confirmed by diagnostic arthroscopy. (Color version of figure is available online.)
J.-W.K. Ko and S. Namdari
4 Future Directions As the quest for improved infection diagnostics continues, several synovial fluid tests have demonstrated some promise for continued evaluation. Leukocyte esterase is an enzyme secreted by neutrophils in the setting of infection. In the knee, leukocyte esterase has been shown to have a high sensitivity and specificity for PJI and it possesses the additional benefit of being easy and cheap to use through a simple colorimetric strip test.35 However, when a substantial amount of blood is present in the synovial fluid sample, the color change of the leukocyte esterase test strip can become masked and cannot be interpreted.36 Unfortunately, it is unknown if this test is useful in diagnosing shoulder PJI. Synovial fluid IL-6 is a marker that has been studied specifically in the shoulder. Its utility appears to be much greater than measuring IL-6 serum levels, and based on a recent study by Frangiamore et al,37 where there is a relatively high sensitivity (87%) and specificity (90%) and when a cutoff value of 359.2 pg/mL is used. Lastly, α-defensin, an antimicrobial peptide expressed in the presence of infection by PMNs, has been shown to have a sensitivity of 63% and a specificity of 95% for diagnosis of shoulder PJI.38 Ultimately, the optimal preoperative diagnostic tool for shoulder PJI still remains elusive, and it is difficult to completely rule out infection before any surgical intervention.
Intraoperative Management Just as clinical signs and symptoms of infection can be deceptive, so can the intraoperative findings. Even in the absence of overt signs of infection such as purulence, osteolysis, and component loosening, a thorough microbiologic, and possibly histologic, evaluation is recommended in all revision surgery. Additionally, a thorough irrigation and debridement of the surgical field should be undertaken as each revision surgery should be considered infected until proven otherwise, particularly given the high rate of unexpected positive cultures in revision shoulder surgery. Rates of unexpected positive cultures in apparently aseptic revision total shoulder surgeries have been reported to be as high as 29%.39 Certainly, these rates may be confounded by contamination of the deep tissues by bacteria from superficial epidermal or dermal layers.
Surgical Pathology The use of surgical pathology has been much more clearly defined in hip and knee PJI with a cutoff of 45 neutrophils per high-powered field being highly diagnostic for the presence of an acute infection.40,41 The role of frozen sections in the shoulder is less well known with limited data in the literature. In a study by Topolski et al,22 they found that 92% of their patients with positive cultures had negative surgical pathology. When American Academy of Orthopaedic Surgeons' guidelines for the number of PMNs per high-power field to diagnose infection in hip and knee are applied for P. acnes PJI in the shoulder, sensitivity is 50% and specificity is 100% for P. acnes. Grosso et al42 found that by changing the guidelines for
P. acnes infection in frozen section to 10 or more PMN's per high-power field, the sensitivity was increased to 72% and the specificity was 100%. Despite the fact that intraoperative frozen sections can be influenced by sampling error and the expertise of the pathologist reviewing the biopsy specimens, intraoperative pathology may still add intraoperative insight into the presence or absence of shoulder PJI.31,42
Tissue Culture In the absence of high-quality preoperative and other intraoperative criteria for determining shoulder PJI, intraoperative cultures remain the gold standard for the diagnosis of shoulder PJI. The exact method of culture, number of cultures, duration of culture growth, and clinical significance of cultures remain debated. In studies of revision shoulder arthroplasty, the rate of positive cultures increases with the number of culture specimens obtained from each shoulder.14 Because of this, we recommend that multiple tissue cultures (minimum of 3) should be obtained from a variety of anatomical locations, including but not limited to the humeral canal, the glenoid, and from any membrane that has formed on or around implants. Pottinger et al14 have shown that the presence of cloudy fluid and membrane formation were associated with significant increase in the likelihood of obtaining a positive P. acnes culture. All cultures should be sent for aerobic, anaerobic, acid-fast bacilli, and fungal culture. It is important to remember that P. acnes is an aerotolerant anaerobic bacteria that can grow on both aerobic and anaerobic culture mediums. The optimal length of culture incubation is also uncertain as prolonged culture is known to increase the ability to isolate fastidious organisms such as P. acnes, but also has the potential to increase the rate of contamination. Many authors have suggested an incubation period of 14 days,23,34,43 and this is our current protocol; however, it should be noted that some authors have suggested incubation periods up to 28 days.14 Additionally, the clinical meaning of positive cultures, particularly with low-virulence organisms, remains ill defined. Although it is possible that a positive culture does represent a true infection, it is also possible that it represents a low-grade colonization of the joint, which may have no influence on the clinical outcome. This theory has been reinforced by multiple studies that have demonstrated successful outcomes and lowinfection rates following unexpected positive cultures during revision shoulder arthroplasty.22,24,39,44 With no confirmatory diagnostic tests, it is currently impossible to clearly delineate between false-positive cultures, true-positive cultures, and non–pathologic-positive cultures.
Management Nonoperative Management Nonsurgical management of a known shoulder PJI should be reserved only for patients where the surgical risk outweighs the morbidity of the patient living with a persistent infection. Nonoperative management typically entails culture-directed antibiotic treatment involving a
The diagnosis and management of PJIs of the shoulder
Figure 3 Radiographs of a commercially available fabricated articulating antibiotic-impregnated cement spacer.
course of intravenous (IV) antibiotics and often lifelong antibiotic suppression. The failure rate with this course of treatment is quite high and reported to be 60% in a small series of patients.1 Therefore, it should only be reserved for the sickest of patients who are unable to undergo surgical intervention.
Operative Management Surgical Debridement With Implant Retention One strategy for managing acute infections includes open surgical debridement of the infected tissues, thorough irrigation of the implant and surrounding tissues, and exchange of all modular components of the implant. This is followed by a course of IV antibiotics based upon intraoperative cultures. This option can be an attractive treatment option to many surgeons and patients, as it avoids the morbidity of complete implant removal. However, the risk of this approach is that it incompletely removes the biofilm of the infecting microbe, which remains adhered to the retained portions of the implant. This makes the patient susceptible to recurrent infection. The shoulder PJI literature suggests that failure rates using this approach can be as high as 50%.5 Specific risks for failure when using this approach in the shoulder have yet to be identified, but it can be inferred from the hip and knee PJI literature that there are higher rates of failure in debridement performed 42 weeks from presentation45 and infections involving more virulent organisms, such as methicillin-resistant Staphylococcus aureus46 and Gramnegative species.47 Therefore, this approach is generally only recommended for acute infections involving nonresistant organisms. Unfortunately, most shoulder PJIs present with a subacute or chronic nature.
5 One-Stage Revision A one-stage revision involves removal of all components of the prosthesis, a thorough surgical debridement and irrigation, and replantation of a new prosthesis during the same surgical procedure. This approach has the theoretical advantage of removing all foreign materials and the biofilm of the infecting organism, which can remain attached to implants. This may be a more cost-effective method to treat shoulder PJI as it can eliminate the need for an additional operative procedure. It may also improve postoperative function of patients compared to two-stage revisions by limiting the morbidity of the additional procedure, permitting more immediate shoulder rehabilitation, and diminishing the soft tissue and bony compromise that often results from multiple revision surgeries. Unfortunately, there are no studies that directly compare onestage and two-stage exchange arthroplasty techniques in a prospective design in shoulder PJI. Ince et al48 reported on a small series of patients who underwent a one-stage revision with antibiotic cement fixation with no reported failures due to recurrent infection. Looking at results following an unexpected positive culture during revision surgery shows that recurrent infection rates are between 5.9% and 25%.22,24,39,44 These studies are an imperfect surrogate to determine the success or failure of a one-stage revision because all cases typically had positive cultures for low-virulence organisms and patients had variable antibiotic management. Based on these findings, onestage revision with exchange of all components appears to be a very reasonable treatment strategy for cases of low suspicion for PJI or infection with low-virulence organisms such as P. acnes. Two-Stage Revision A two-stage revision involves complete removal of all components of the implant with placement of a temporary antibioticimpregnated cement spacer. Following a course of IV antibiotics, if the infection is deemed to have been adequately treated, a second reimplantation operation is undertaken. Some surgeons have advocated for use of commercially produced articulating hemiarthroplasty spacers as some patients are satisfied enough with the function of an articulating spacer that a second stage reimplantation is not needed49 (Fig. 3). A two-stage approach has the most data to support its use in the shoulder PJI literature. Additionally, it allows the surgeon to more effectively plan for the revision implantation because uncertain variables such as tissue quality and available bone stock can be assessed during the first stage of the revision. In grossly infected shoulder prostheses and infections with virulent organisms, this is our current preferred approach. Reported rates of reinfection following a two-stage revision are variable but are noted to be between 0% and 36%.1,5,20,50-52 Salvage Procedures: Resection Arthroplasty and Arthrodesis. In patients with lower functional demands, high risk for reinfection, extensive bone loss, or high surgical risk, a resection arthroplasty may be the best option for treatment. A resection arthroplasty is good for infection eradication, reasonable for pain relief, but poor for functional outcome. Currently, we reserve use of this approach primarily for patients with multiple-failed infected shoulder arthroplasty
6 in whom any attempt at surgical reconstruction would pose a high risk for failure or reinfection. Another potential option for treatment is shoulder arthrodesis. This may be an option for younger patients with limited options for reconstruction, once the underlying infection has been adequately treated. However, arthrodesis in the setting of multiple-failed arthroplasties can be challenging due to bone loss. Therefore, advanced bone grafting techniques may have to be implemented and the implanted hardware can potentially become a source for reinfection.53,54
Conclusion The diagnosis and management of shoulder PJI remains a challenging clinical problem. Historic treatment strategies have largely been based upon the literature on PJI of the hip and knee. It is now becoming increasingly recognized that the unique microbiome makes shoulder PJI distinct from other regions of the body. This has made the detection and treatment of shoulder PJI more difficult and complex than previously understood. Additionally, the clinical significance of revision shoulder arthroplasties with cultures positive for low-virulence organisms continues to be a topic of debate. As our understanding of shoulder PJI evolves, it remains an area in need of continued research with the hope of developing better evidence-based guidelines for its diagnosis and management.
References 1. Coste JS, Reig S, Trojani C, et al: The management of infection in arthroplasty of the shoulder. J Bone Joint Surg Br 86:65-69, 2004. [PubMed PMID: 14765868] 2. Day JS, Paxton ES, Lau E, et al: Use of reverse total shoulder arthroplasty in the Medicare population. J Shoulder Elbow Surg 24:766-772, 2015. http: //dx.doi.org/10.1016/j.jse.2014.12.023. [PubMed PMID: 25704826] 3. Dodson CC, Craig EV, Cordasco FA: Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge. J Shoulder Elbow Surg 19:303-307, 2010. http://dx.doi.org/10.1016/j.jse.2009.07.065. [Pub Med PMID: 19884021] 4. Singh JA, Sperling JW, Schleck C, et al: Periprosthetic infections after total shoulder arthroplasty: A 33-year perspective. J Shoulder Elbow Surg 21:1534-1541, 2012. http://dx.doi.org/10.1016/j.jse.2012.01.006. [PubMed PMID: 22516570; PubMed Central PMCID: PMC3586318] 5. Sperling JW, Kozak TK, Hanssen AD, et al: Infection after shoulder arthroplasty. Clin Orthop Relat Res 382:206-216, 2001. [PubMed PMID: 11153989] 6. Padegimas EM, Maltenfort M, Ramsey ML, et al: Periprosthetic shoulder infection in the United States: Incidence and economic burden. J Shoulder Elbow Surg 24:741-746, 2015. http://dx.doi.org/10.1016/j.jse.2014.11. 044. [PubMed PMID: 25595360] 7. Ramsey ML, Fenlin Jr. JM: Use of an antibiotic-impregnated bone cement block in the revision of an infected shoulder arthroplasty. J Shoulder Elbow Surg 5:479-482, 1996. [PubMed PMID: 8981275] 8. Kim SH, Wise BL, Zhang Y, et al: Increasing incidence of shoulder arthroplasty in the United States. J Bone Joint Surg Am 93:2249-2254, 2011. http://dx.doi.org/10.2106/JBJS.J.01994. [PubMed PMID: 22258770] 9. Matsen 3rd FA, Butler-Wu S, Carofino BC, et al: Origin of Propionibacterium in surgical wounds and evidence-based approach for culturing Propionibacterium from surgical sites. J Bone Joint Surg Am 95: e1811-e1817, 2013. http://dx.doi.org/10.2106/JBJS.L.01733. [PubMed PMID: 24306704]
J.-W.K. Ko and S. Namdari 10. Lee MJ, Pottinger PS, Butler-Wu S, et al: Propionibacterium persists in the skin despite standard surgical preparation. J Bone Joint Surg Am 96:1447-1450, 2014. http://dx.doi.org/10.2106/JBJS.M.01474. [PubMed PMID: 25187583] 11. Matsen 3rd FA, Russ SM, Bertelsen A, et al: Propionibacterium can be isolated from deep cultures obtained at primary arthroplasty despite intravenous antimicrobial prophylaxis. J Shoulder Elbow Surg 24:844-847, 2015. http://dx.doi.org/10.1016/j.jse.2014.10.016. [Pub Med PMID: 25547858] 12. Maccioni CB, Woodbridge AB, Balestro JC: Low rate of Propionibacterium acnes in arthritic shoulders undergoing primary total shoulder replacement surgery using a strict specimen collection technique. J Shoulder Elbow Surg:. http://dx.doi.org/10.1016/j.jse.2014.12.026. [PubMed PMID: 25700640] 13. Levy O, Iyer S, Atoun E: Propionibacterium acnes: An underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg 22:505-511, 2013. http://dx.doi.org/10.1016/j.jse.2012.07.007. [Pub Med PMID: 22981447] 14. Pottinger P, Butler-Wu S, Neradilek MB: 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. J Bone Joint Surg Am 94:2075-2083, 2012. http://dx.doi.org/ 10.2106/JBJS.K.00861. [PubMed PMID: 23172325] 15. Singh JA, Sperling JW, Schleck C, et al: Periprosthetic infections after shoulder hemiarthroplasty. J Shoulder Elbow Surg 21:1304-1309, 2012. http://dx.doi.org/10.1016/j.jse.2011.08.067. [PubMed PMID: 22154310; PubMed Central PMCID: PMC3310339] 16. Cheung EV, Sperling JW, Cofield RH: Infection associated with hematoma formation after shoulder arthroplasty. Clin Orthop Relat Res 466:1363-1367, 2008. http://dx.doi.org/10.1007/s11999-008-0226-3. [PubMed PMID: 18421541; PubMed Central PMCID: PMC2384030] 17. Pochi PE, Strauss JS, Downing DT: Age-related changes in sebaceous gland activity. J Invest Dermatol 73:108-111, 1979. [PubMed PMID: 448169] 18. Zouboulis CC: Acne and sebaceous gland function. Clin Dermatol 22:360-366, 2004. http://dx.doi.org/10.1016/j.clindermatol.2004.03. 004. [PubMed PMID: 15556719] 19. Cheung E, Willis M, Walker M, et al: Complications in reverse total shoulder arthroplasty. J Am Acad Orthop Surg 19:439-449, 2011. [PubMed PMID: 21724923] 20. Dines JS, Fealy S, Strauss EJ: Outcomes analysis of revision total shoulder replacement. J Bone Joint Surg Am 88:1494-1500, 2006. http://dx.doi. org/10.2106/JBJS.D.02946. [PubMed PMID: 16818975] 21. Palestro CJ: Nuclear medicine and the failed joint replacement: Past, present, and future. World J Radiol 6:446-458, 2014. http://dx.doi.org/ 10.4329/wjr.v6.i7.446. [PubMed PMID: 25071885; PubMed Central PMCID: PMC4109096] 22. Topolski MS, Chin PY, Sperling JW, et al: Revision shoulder arthroplasty with positive intraoperative cultures: The value of preoperative studies and intraoperative histology. J Shoulder Elbow Surg 15:402-406, 2006. http://dx.doi.org/10.1016/j.jse.2005.10.001. [PubMed PMID: 16831641] 23. Millett PJ, Yen YM, Price CS, et al: Propionibacterium acnes infection as an occult cause of postoperative shoulder pain: A case series. Clin Orthop Relat Res 469:2824-2830, 2011. http://dx.doi.org/10.1007/s11999-0111767-4. [PubMed PMID: 21240577; PubMed Central PMCID: PMC 3171528] 24. Foruria AM, Fox TJ, Sperling JW, et al: Clinical meaning of unexpected positive cultures (UPC) in revision shoulder arthroplasty. J Shoulder Elbow Surg 22:620-627, 2013. http://dx.doi.org/10.1016/j.jse.2012.07. 017. [PubMed PMID: 22981448] 25. Parvizi J, Zmistowski B, Berbari EF: New definition for periprosthetic joint infection: From the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 469:2992-2994, 2011. http://dx.doi.org/10.1007/ s11999-011-2102-9. [PubMed PMID: 21938532; PubMed Central PMCID: PMC3183178] 26. Piper KE, Fernandez-Sampedro M, Steckelberg KE: C-reactive protein, erythrocyte sedimentation rate and orthopedic implant infection. PLoS One 5:e9358, 2010. http://dx.doi.org/10.1371/journal.pone.0009358. [PubMed PMID: 20179760; PubMed Central PMCID: PMC2825262]
The diagnosis and management of PJIs of the shoulder 27. Di Cesare PE, Chang E, Preston CF, et al: Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am 87:1921-1927, 2005. http://dx.doi.org/10.2106/JBJS. D.01803. [PubMed PMID: 16140805] 28. Grosso MJ, Frangiamore SJ, Saleh A, et al: Poor utility of serum interleukin-6 levels to predict indolent periprosthetic shoulder infections. J Shoulder Elbow Surg 23:1277-1281, 2014. http://dx.doi.org/10.1016/j. jse.2013.12.023. [PubMed PMID: 24725902] 29. Villacis D, Merriman JA, Yalamanchili R, et al: Serum interleukin-6 as a marker of periprosthetic shoulder infection. J Bone Joint Surg Am 96:41-45, 2014. http://dx.doi.org/10.2106/JBJS.L.01634. [PubMed PMID: 24382723] 30. Della Valle C, Parvizi J, Bauer TW: American Academy of Orthopaedic Surgeons clinical practice guideline onthe diagnosis of periprosthetic joint infections of the hip and knee. J Bone Joint Surg Am 93:1355-1357, 2011. http://dx.doi.org/10.2106/JBJS.9314ebo. [PubMed PMID: 21792503] 31. Della Valle C, Parvizi J, Bauer TW, et al: Diagnosis of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg 18:760-770, 2010. [PubMed PMID: 21119142] 32. Barrack RL, Jennings RW, Wolfe MW, et al: The Coventry Award. The value of preoperative aspiration before total knee revision. Clin Orthop Relat Res 345:8-16, 1997. [PubMed PMID: 9418615] 33. Dilisio MF, Miller LR, Warner JJ, et al: Arthroscopic tissue culture for the evaluation of periprosthetic shoulder infection. J Bone Joint Surg Am 96:1952-1958, 2014. http://dx.doi.org/10.2106/JBJS.M.01512. [PubMed PMID: 25471909] 34. Morman M, Fowler RL, Sanofsky B, et al: Arthroscopic tissue biopsy for evaluation of infection before revision arthroplasty. J Shoulder Elbow Surg 20:e15-e22, 2011. http://dx.doi.org/10.1016/j.jse.2010.11.015. [PubMed PMID: 21330156] 35. Parvizi J, Jacovides C, Antoci V, et al: Diagnosis of periprosthetic joint infection: The utility of a simple yet unappreciated enzyme. J Bone Joint Surg Am 93:2242-2248, 2011. http://dx.doi.org/10.2106/JBJS.J.01413. [PubMed PMID: 22258769] 36. Tischler EH, Cavanaugh PK, Parvizi J: Leukocyte esterase strip test: Matched for musculoskeletal infection society criteria. J Bone Joint Surg Am 96:1917-1920, 2014. http://dx.doi.org/10.2106/JBJS.M.01591. [PubMed PMID: 25410511] 37. Frangiamore SJ, Saleh A, Kovac MF, et al: Synovial fluid interleukin-6 as a predictor of periprosthetic shoulder infection. J Bone Joint Surg Am 97:63-70, 2015. http://dx.doi.org/10.2106/JBJS.N.00104. [PubMed PMID: 25568396] 38. Frangiamore SJ, Saleh A, Grosso MJ, et al: Alpha-defensin as a predictor of periprosthetic shoulder infection. J Shoulder Elbow Surg:. http://dx.doi. org/10.1016/j.jse.2014.12.021. [PubMed PMID: 25672257] 39. Kelly 2nd JD, Hobgood ER: Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res 467:2343-2348, 2009. http://dx.doi. org/10.1007/s11999-009-0875-x. [PubMed PMID: 19434469; PubMed Central PMCID: PMC2866925] 40. Della Valle CJ, Bogner E, Desai P, et al: Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation after hip or knee resection arthroplasty for the treatment of infection. J Bone Joint Surg Am 81:684-689, 1999. [PubMed PMID: 10360696]
7 41. Lonner JH, Desai P, Dicesare PE, et al: The reliability of analysis of intraoperative frozen sections for identifying active infection during revision hip or knee arthroplasty. J Bone Joint Surg Am 78:1553-1558, 1996. [PubMed PMID: 8876584] 42. Grosso MJ, Frangiamore SJ, Ricchetti ET, et al: Sensitivity of frozen section histology for identifying Propionibacterium acnes infections in revision shoulder arthroplasty. J Bone Joint Surg Am 96:442-447, 2014. http://dx. doi.org/10.2106/JBJS.M.00258. [PubMed PMID: 24647499] 43. Lutz MF, Berthelot P, Fresard A, et al: Arthroplastic and osteosynthetic infections due to Propionibacterium acnes: A retrospective study of 52 cases, 1995-2002. Eur J Clin Microbiol Infect Dis 24:739-744, 2005. http: //dx.doi.org/10.1007/s10096-005-0040-8. [PubMed PMID: 16328558] 44. Grosso MJ, Sabesan VJ, Ho JC, et al: Reinfection rates after 1-stage revision shoulder arthroplasty for patients with unexpected positive intraoperative cultures. J Shoulder Elbow Surg 21:754-758, 2012. http://dx.doi.org/ 10.1016/j.jse.2011.08.052. [PubMed PMID: 22305921] 45. Crockarell JR, Hanssen AD, Osmon DR, et al: Treatment of infection with debridement and retention of the components following hip arthroplasty. J Bone Joint Surg Am 80:1306-1313, 1998. [PubMed PMID: 9759815] 46. Bradbury T, Fehring TK, Taunton M, et al: The fate of acute methicillinresistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. J Arthroplasty 24:101-104, 2009. http://dx.doi.org/10.1016/j.arth.2009.04.028 (suppl 6) [PubMed PMID: 19553077] 47. Schoifet SD, Morrey BF: Treatment of infection after total knee arthroplasty by debridement with retention of the components. J Bone Joint Surg Am 72:1383-1390, 1990. [PubMed PMID: 2229118] 48. Ince A, Seemann K, Frommelt L, et al: One-stage exchange shoulder arthroplasty for peri-prosthetic infection. J Bone Joint Surg Br 87: 814-818, 2005. http://dx.doi.org/10.1302/0301-620X.87B6.15920. [PubMed PMID: 15911665] 49. Coffey MJ, Ely EE, Crosby LA: Treatment of glenohumeral sepsis with a commercially produced antibiotic-impregnated cement spacer. J Shoulder Elbow Surg 19:868-873, 2010. http://dx.doi.org/10.1016/j.jse.2010.01. 012. [PubMed PMID: 20392651] 50. Strickland JP, Sperling JW, Cofield RH: The results of two-stage reimplantation for infected shoulder replacement. J Bone Joint Surg Br 90:460-465, 2008. http://dx.doi.org/10.1302/0301-620X.90B4.20002. [PubMed PMID: 18378920] 51. Weber P, Utzschneider S, Sadoghi P, et al: Management of the infected shoulder prosthesis: A retrospective analysis and review of the literature. Int Orthop 35:365-373, 2011. http://dx.doi.org/10.1007/s00264-0101019-3. [PubMed PMID: 20405287; PubMed Central PMCID: PMC 3047637] 52. Seitz Jr. WH, Damacen H: Staged exchange arthroplasty for shoulder sepsis. J Arthroplasty 17:36-40, 2002 (4 suppl 1) [PubMed PMID: 12068401] 53. Safran O, Iannotti JP: Arthrodesis of the shoulder. J Am Acad Orthop Surg 14:145-153, 2006. [PubMed PMID: 16520365] 54. Bilgin SS: Reconstruction of proximal humeral defects with shoulder arthrodesis using free vascularized fibular graft. J Bone Joint Surg Am 94: e94, 2012. http://dx.doi.org/10.2106/JBJS.J.01823. [PubMed PMID: 22760395]
KEYWORDS periprosthetic infection, shoulder arthroplasty, complications
Introduction
P
eriprosthetic joint infections (PJIs) of the shoulder are a relatively uncommon complication of shoulder arthroplasty with studies suggesting a rate between 0.7% and 1.8% in primary shoulder arthroplasty and up to 15.4% in revision arthroplasty.1-7 National rates of PJI involving the shoulder have remained relatively constant over the past decade, suggesting that surgeons are not much better at preventing them, and that the number of infections encountered would mirror the increase in shoulder arthroplasty utilization.6 Projections suggest that 46000 new shoulder PJI cases would be encountered each year in the most conservative of estimates.6,8 Although much of our historical understanding of the diagnosis and management of shoulder PJI has been extrapolated from the literature on hip and knee PJI, it is now understood that the unique microbiome of the shoulder may make correlations between lower extremity PJI and shoulder
*Orthopedic Physician Associates at Swedish Orthopedic Institute, Seattle, WA. †The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA. *Address reprint requests to Surena Namdari, MD, MSc, The Rothman Institute at Thomas Jefferson University Hospital, Philadelphia, PA E-mail: [email protected]
http://dx.doi.org/10.1053/j.oto.2015.12.001 1048-6666//& 2016 Elsevier Inc. All rights reserved.
PJI inaccurate. It is becoming increasingly recognized that lowvirulence organisms such as Propionibacterium acnes (P. acnes) and coagulase-negative Staphylococcus species play a more prominent role in PJI involving the shoulder.3,9 This not only underscores the diagnostic challenge of identifying these organisms, but also suggests that the historic rates of shoulder PJI likely underestimate the true incidence of this challenging problem. As our diagnostic tools improve and evolve, it now seems that the harder we search for shoulder PJI, the more likely we are to find it. The goal of this article would be to summarize our current understanding of the diagnosis and management of shoulder PJI through an evidence-based approach.
Clinical Evaluation It is nearly impossible to completely rule out the possibility of infection in any patient who presents to the hospital with a painful or poorly functioning shoulder arthroplasty with current diagnostic tools. Because of this, the highest index of suspicion must be maintained through all steps of the diagnostic workup and any revision procedures undertaken. It is important to remember that, even in the face of obvious mechanical or soft tissue failure, there may be concomitant infection present within the shoulder. One of the reasons for this vigilance is that we now understand that the usual sterile 1
J.-W.K. Ko and S. Namdari
2 preparation of the shoulder is not sufficient to eliminate P. acnes that densely populates the sebaceous glands within the dermal layer of the shoulder.10 Therefore, it is safe to assume that every surgical wound about the shoulder has the potential to contaminate the deep underlying tissues, and studies have suggested that this is likely the case.11-13 The identified risk factors for developing a PJI of the shoulder include male sex,4,14 younger age,4 posttraumatic arthroplasty,15 and the presence of a postoperative hematoma.16 Owing to the higher bacterial prevalence within hair follicles and pores, P. acnes is more commonly associated with men. A possible explanation for the decrease in infection risk with age may relate to the decrease in sebaceous gland secretion with age, resulting from the concomitant decrease in the endogenous production of androgens.17,18 Additionally, infection may be more common following reverse total shoulder arthroplasty19 and revision surgery.20 Other comorbid conditions such as obesity, diabetes, smoking, malnutrition, chronic kidney or liver disease, and immunosuppression have yet to be identified as risk factors, although this is likely because of the fact that most of the current studies have been underpowered to detect a difference in these parameters. Clinical signs and symptoms can vary and are often nonspecific. Although overt signs of infection, such as fevers, chills, erythema, swelling, or a draining sinuse, are easy to identify, they typically only occur with more virulent organisms.5 Some of the most common symptoms, including pain and stiffness, are ubiquitous in nearly all poorly functioning shoulder arthroplasties, but are often the only signs present with low-virulence organisms such as P. acnes.14 A thorough clinical history should be elicited,
A
noting any postoperative wound-healing issues, superficial wound infections, and potential sources for hematogenous seeding of the shoulder joint.
Diagnostic Evaluation Radiologic Evaluation The diagnostic evaluation of a potentially infected shoulder arthroplasty typically starts with radiographs. Radiographs allow for the initial evaluation of other potential causes of a failed shoulder arthroplasty and may demonstrate hallmark findings of infected arthroplasty. Although radiographs cannot confirm an infection, humeral osteolysis, and component loosening have been associated with PJI in the shoulder14 (Fig. 1). More suppurative infections may also demonstrate joint effusion, periosteal reaction, or endosteal scalloping on radiographs. The 3-dimensional imaging including computed tomography scans and magnetic resonance imaging of the shoulder is not typically helpful in the diagnosis of shoulder PJI. Largely, this is because the existing implant can create a substantial amount of artifact on advanced imaging, making interpretation of the study very difficult. However, with metal suppression techniques, these studies are often ordered, more for the purpose of determining rotator cuff integrity and bone loss for preoperative planning, than as a diagnostic tool for shoulder PJI. Radionuclide imaging has not been well studied as a diagnostic tool for identifying infection in shoulder arthroplasty. A labeled white blood cell (leukocyte) imaging study
B
Figure 1 Sequential radiographs of an infected total shoulder arthroplasty, which demonstrate progressive humeral osteolysis most prominent in the inferomedial calcar (A) at 6 years and (B) at 7 years.
The diagnosis and management of PJIs of the shoulder holds the most promise as other radionuclide studies would not differentiate between septic and aseptic loosening. The role of radionuclide imaging in the lower extremity PJI has been studied with unknown benefit.21 Based on the current literature, it is impossible to recommend for or against radionuclide imaging in the diagnosis of shoulder PJI.
Serologic Evaluation Serologic testing is a standard part of the evaluation of any potential PJI. Acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can be elevated in the face of infection, but are nonspecific for infection and can be elevated with any ongoing inflammatory process. More importantly, they are often normal with the lowgrade infections that commonly afflict the shoulder.3,22,23 In a series of 107 patients with unexpected positive intraoperative cultures, Foruria et al24 reported that the ESR was positive in only 5% and the CRP was positive in only 12%. This is in contrast to PJI of the hip and knee where inflammatory markers have a relatively high-negative predictive value and are one of the key diagnostic tests.25,26 Owing to the poor diagnostic accuracy of ESR and CRP, interleukin-6 (IL-6) is a proinflammatory cytokine, which has also been evaluated for identifying shoulder PJI. IL-6 has been used both as a serologic test and as a synovial fluid test, the latter of which would be discussed in a separate section. As a serologic test, IL-6 has shown promise for use in hip and knee PJI.27 However, much like the use of ESR and CRP, the same promise has not been realized in shoulder PJI. Studies have demonstrated the poor sensitivity of serum IL-6 in infected shoulder arthroplasty, making it of limited utility as a diagnostic test.28,29
Synovial Fluid Evaluation The utility of a shoulder aspiration to evaluate for shoulder PJI remains a subject of debate. Although aspiration is a relatively low-risk procedure that can sometimes be performed in the office setting with or without imaging guidance, it can often be difficult to obtain enough fluid for analysis. Recommendations from the hip and knee PJI literature suggest that aspirations should be performed if there are elevated inflammatory markers.30 However, we know that ESR and CRP are often normal in the setting of shoulder PJI. Additionally, infections with low-virulence organisms do not necessarily generate much of a host reaction or enough excess synovial fluid to be easily obtained. There also remains the hypothetical risk for seeding a noninfected joint or falsepositive result through P. acnes contamination with a needle puncturing an underlying sebaceous gland. Until the role of aspiration is more clearly defined in the literature, whether or not to perform an aspiration remains the preference of the treating surgeon. If an aspiration is successful in obtaining enough fluid for analysis, the fluid should be sent for synovial leukocyte count, cell differential, and culture, at a minimum.
3 Synovial Leukocyte Count In the hip and knee literature, a threshold of 1700 cells/μL with 460% polymorphonuclear (PMN) cells has been suggested as a cutoff for being highly suspicious for infection.31 In the absence of studies looking specifically at thresholds in shoulder PJI, these numbers serve as a rough guideline for synovial fluid analysis in the prosthetic shoulder as well. However, it is likely that thresholds in the hip and knee are different from thresholds in the shoulder, particularly with the higher prevalence of low-virulence organisms. With this in mind, a significantly elevated synovial leukocyte count may be diagnostic for infection; however, a low or “normal” synovial leukocyte count cannot definitely rule out the presence of infection. Culture Synovial fluid should also be sent for aerobic and anaerobic cultures. It is important to request that the laboratory hold the cultures for a minimum of 14 days in an effort to isolate fastidious organisms such as P. acnes. In the knee literature, it is known that the false-negative culture rates can be as high as 34% of cultures from preoperative aspiration.32 The sensitivity and specificity of cultures from preoperative shoulder aspirates has not been studied; however, given the relatively low sensitivity from the available total joint literature, a negative culture cannot definitively rule out the presence of infection. Rather, cultures can only be used to increase the suspicion for true infection. Diagnostic Arthroscopy A method for evaluating a potentially infected shoulder arthroplasty is use of diagnostic arthroscopy. This method has the advantage of being able to obtain tissue cultures from the shoulder joint, which has been shown to more reliable than preoperative aspiration results.33,34 Additionally, this approach allows the opportunity to assess for other causes of a painful shoulder arthroplasty, including glenoid loosening or rotator cuff failure (Fig. 2). A diagnostic arthroscopy avoids the morbidity of an open surgery; however, if an infection is discovered, a secondary procedure may be needed. We reserve this approach for patients where other diagnostic tests have not given a clear reason for failure or poor function.
Figure 2 Arthroscopic image of a loose glenoid in an infected shoulder arthroplasty confirmed by diagnostic arthroscopy. (Color version of figure is available online.)
J.-W.K. Ko and S. Namdari
4 Future Directions As the quest for improved infection diagnostics continues, several synovial fluid tests have demonstrated some promise for continued evaluation. Leukocyte esterase is an enzyme secreted by neutrophils in the setting of infection. In the knee, leukocyte esterase has been shown to have a high sensitivity and specificity for PJI and it possesses the additional benefit of being easy and cheap to use through a simple colorimetric strip test.35 However, when a substantial amount of blood is present in the synovial fluid sample, the color change of the leukocyte esterase test strip can become masked and cannot be interpreted.36 Unfortunately, it is unknown if this test is useful in diagnosing shoulder PJI. Synovial fluid IL-6 is a marker that has been studied specifically in the shoulder. Its utility appears to be much greater than measuring IL-6 serum levels, and based on a recent study by Frangiamore et al,37 where there is a relatively high sensitivity (87%) and specificity (90%) and when a cutoff value of 359.2 pg/mL is used. Lastly, α-defensin, an antimicrobial peptide expressed in the presence of infection by PMNs, has been shown to have a sensitivity of 63% and a specificity of 95% for diagnosis of shoulder PJI.38 Ultimately, the optimal preoperative diagnostic tool for shoulder PJI still remains elusive, and it is difficult to completely rule out infection before any surgical intervention.
Intraoperative Management Just as clinical signs and symptoms of infection can be deceptive, so can the intraoperative findings. Even in the absence of overt signs of infection such as purulence, osteolysis, and component loosening, a thorough microbiologic, and possibly histologic, evaluation is recommended in all revision surgery. Additionally, a thorough irrigation and debridement of the surgical field should be undertaken as each revision surgery should be considered infected until proven otherwise, particularly given the high rate of unexpected positive cultures in revision shoulder surgery. Rates of unexpected positive cultures in apparently aseptic revision total shoulder surgeries have been reported to be as high as 29%.39 Certainly, these rates may be confounded by contamination of the deep tissues by bacteria from superficial epidermal or dermal layers.
Surgical Pathology The use of surgical pathology has been much more clearly defined in hip and knee PJI with a cutoff of 45 neutrophils per high-powered field being highly diagnostic for the presence of an acute infection.40,41 The role of frozen sections in the shoulder is less well known with limited data in the literature. In a study by Topolski et al,22 they found that 92% of their patients with positive cultures had negative surgical pathology. When American Academy of Orthopaedic Surgeons' guidelines for the number of PMNs per high-power field to diagnose infection in hip and knee are applied for P. acnes PJI in the shoulder, sensitivity is 50% and specificity is 100% for P. acnes. Grosso et al42 found that by changing the guidelines for
P. acnes infection in frozen section to 10 or more PMN's per high-power field, the sensitivity was increased to 72% and the specificity was 100%. Despite the fact that intraoperative frozen sections can be influenced by sampling error and the expertise of the pathologist reviewing the biopsy specimens, intraoperative pathology may still add intraoperative insight into the presence or absence of shoulder PJI.31,42
Tissue Culture In the absence of high-quality preoperative and other intraoperative criteria for determining shoulder PJI, intraoperative cultures remain the gold standard for the diagnosis of shoulder PJI. The exact method of culture, number of cultures, duration of culture growth, and clinical significance of cultures remain debated. In studies of revision shoulder arthroplasty, the rate of positive cultures increases with the number of culture specimens obtained from each shoulder.14 Because of this, we recommend that multiple tissue cultures (minimum of 3) should be obtained from a variety of anatomical locations, including but not limited to the humeral canal, the glenoid, and from any membrane that has formed on or around implants. Pottinger et al14 have shown that the presence of cloudy fluid and membrane formation were associated with significant increase in the likelihood of obtaining a positive P. acnes culture. All cultures should be sent for aerobic, anaerobic, acid-fast bacilli, and fungal culture. It is important to remember that P. acnes is an aerotolerant anaerobic bacteria that can grow on both aerobic and anaerobic culture mediums. The optimal length of culture incubation is also uncertain as prolonged culture is known to increase the ability to isolate fastidious organisms such as P. acnes, but also has the potential to increase the rate of contamination. Many authors have suggested an incubation period of 14 days,23,34,43 and this is our current protocol; however, it should be noted that some authors have suggested incubation periods up to 28 days.14 Additionally, the clinical meaning of positive cultures, particularly with low-virulence organisms, remains ill defined. Although it is possible that a positive culture does represent a true infection, it is also possible that it represents a low-grade colonization of the joint, which may have no influence on the clinical outcome. This theory has been reinforced by multiple studies that have demonstrated successful outcomes and lowinfection rates following unexpected positive cultures during revision shoulder arthroplasty.22,24,39,44 With no confirmatory diagnostic tests, it is currently impossible to clearly delineate between false-positive cultures, true-positive cultures, and non–pathologic-positive cultures.
Management Nonoperative Management Nonsurgical management of a known shoulder PJI should be reserved only for patients where the surgical risk outweighs the morbidity of the patient living with a persistent infection. Nonoperative management typically entails culture-directed antibiotic treatment involving a
The diagnosis and management of PJIs of the shoulder
Figure 3 Radiographs of a commercially available fabricated articulating antibiotic-impregnated cement spacer.
course of intravenous (IV) antibiotics and often lifelong antibiotic suppression. The failure rate with this course of treatment is quite high and reported to be 60% in a small series of patients.1 Therefore, it should only be reserved for the sickest of patients who are unable to undergo surgical intervention.
Operative Management Surgical Debridement With Implant Retention One strategy for managing acute infections includes open surgical debridement of the infected tissues, thorough irrigation of the implant and surrounding tissues, and exchange of all modular components of the implant. This is followed by a course of IV antibiotics based upon intraoperative cultures. This option can be an attractive treatment option to many surgeons and patients, as it avoids the morbidity of complete implant removal. However, the risk of this approach is that it incompletely removes the biofilm of the infecting microbe, which remains adhered to the retained portions of the implant. This makes the patient susceptible to recurrent infection. The shoulder PJI literature suggests that failure rates using this approach can be as high as 50%.5 Specific risks for failure when using this approach in the shoulder have yet to be identified, but it can be inferred from the hip and knee PJI literature that there are higher rates of failure in debridement performed 42 weeks from presentation45 and infections involving more virulent organisms, such as methicillin-resistant Staphylococcus aureus46 and Gramnegative species.47 Therefore, this approach is generally only recommended for acute infections involving nonresistant organisms. Unfortunately, most shoulder PJIs present with a subacute or chronic nature.
5 One-Stage Revision A one-stage revision involves removal of all components of the prosthesis, a thorough surgical debridement and irrigation, and replantation of a new prosthesis during the same surgical procedure. This approach has the theoretical advantage of removing all foreign materials and the biofilm of the infecting organism, which can remain attached to implants. This may be a more cost-effective method to treat shoulder PJI as it can eliminate the need for an additional operative procedure. It may also improve postoperative function of patients compared to two-stage revisions by limiting the morbidity of the additional procedure, permitting more immediate shoulder rehabilitation, and diminishing the soft tissue and bony compromise that often results from multiple revision surgeries. Unfortunately, there are no studies that directly compare onestage and two-stage exchange arthroplasty techniques in a prospective design in shoulder PJI. Ince et al48 reported on a small series of patients who underwent a one-stage revision with antibiotic cement fixation with no reported failures due to recurrent infection. Looking at results following an unexpected positive culture during revision surgery shows that recurrent infection rates are between 5.9% and 25%.22,24,39,44 These studies are an imperfect surrogate to determine the success or failure of a one-stage revision because all cases typically had positive cultures for low-virulence organisms and patients had variable antibiotic management. Based on these findings, onestage revision with exchange of all components appears to be a very reasonable treatment strategy for cases of low suspicion for PJI or infection with low-virulence organisms such as P. acnes. Two-Stage Revision A two-stage revision involves complete removal of all components of the implant with placement of a temporary antibioticimpregnated cement spacer. Following a course of IV antibiotics, if the infection is deemed to have been adequately treated, a second reimplantation operation is undertaken. Some surgeons have advocated for use of commercially produced articulating hemiarthroplasty spacers as some patients are satisfied enough with the function of an articulating spacer that a second stage reimplantation is not needed49 (Fig. 3). A two-stage approach has the most data to support its use in the shoulder PJI literature. Additionally, it allows the surgeon to more effectively plan for the revision implantation because uncertain variables such as tissue quality and available bone stock can be assessed during the first stage of the revision. In grossly infected shoulder prostheses and infections with virulent organisms, this is our current preferred approach. Reported rates of reinfection following a two-stage revision are variable but are noted to be between 0% and 36%.1,5,20,50-52 Salvage Procedures: Resection Arthroplasty and Arthrodesis. In patients with lower functional demands, high risk for reinfection, extensive bone loss, or high surgical risk, a resection arthroplasty may be the best option for treatment. A resection arthroplasty is good for infection eradication, reasonable for pain relief, but poor for functional outcome. Currently, we reserve use of this approach primarily for patients with multiple-failed infected shoulder arthroplasty
6 in whom any attempt at surgical reconstruction would pose a high risk for failure or reinfection. Another potential option for treatment is shoulder arthrodesis. This may be an option for younger patients with limited options for reconstruction, once the underlying infection has been adequately treated. However, arthrodesis in the setting of multiple-failed arthroplasties can be challenging due to bone loss. Therefore, advanced bone grafting techniques may have to be implemented and the implanted hardware can potentially become a source for reinfection.53,54
Conclusion The diagnosis and management of shoulder PJI remains a challenging clinical problem. Historic treatment strategies have largely been based upon the literature on PJI of the hip and knee. It is now becoming increasingly recognized that the unique microbiome makes shoulder PJI distinct from other regions of the body. This has made the detection and treatment of shoulder PJI more difficult and complex than previously understood. Additionally, the clinical significance of revision shoulder arthroplasties with cultures positive for low-virulence organisms continues to be a topic of debate. As our understanding of shoulder PJI evolves, it remains an area in need of continued research with the hope of developing better evidence-based guidelines for its diagnosis and management.
References 1. Coste JS, Reig S, Trojani C, et al: The management of infection in arthroplasty of the shoulder. J Bone Joint Surg Br 86:65-69, 2004. [PubMed PMID: 14765868] 2. Day JS, Paxton ES, Lau E, et al: Use of reverse total shoulder arthroplasty in the Medicare population. J Shoulder Elbow Surg 24:766-772, 2015. http: //dx.doi.org/10.1016/j.jse.2014.12.023. [PubMed PMID: 25704826] 3. Dodson CC, Craig EV, Cordasco FA: Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge. J Shoulder Elbow Surg 19:303-307, 2010. http://dx.doi.org/10.1016/j.jse.2009.07.065. [Pub Med PMID: 19884021] 4. Singh JA, Sperling JW, Schleck C, et al: Periprosthetic infections after total shoulder arthroplasty: A 33-year perspective. J Shoulder Elbow Surg 21:1534-1541, 2012. http://dx.doi.org/10.1016/j.jse.2012.01.006. [PubMed PMID: 22516570; PubMed Central PMCID: PMC3586318] 5. Sperling JW, Kozak TK, Hanssen AD, et al: Infection after shoulder arthroplasty. Clin Orthop Relat Res 382:206-216, 2001. [PubMed PMID: 11153989] 6. Padegimas EM, Maltenfort M, Ramsey ML, et al: Periprosthetic shoulder infection in the United States: Incidence and economic burden. J Shoulder Elbow Surg 24:741-746, 2015. http://dx.doi.org/10.1016/j.jse.2014.11. 044. [PubMed PMID: 25595360] 7. Ramsey ML, Fenlin Jr. JM: Use of an antibiotic-impregnated bone cement block in the revision of an infected shoulder arthroplasty. J Shoulder Elbow Surg 5:479-482, 1996. [PubMed PMID: 8981275] 8. Kim SH, Wise BL, Zhang Y, et al: Increasing incidence of shoulder arthroplasty in the United States. J Bone Joint Surg Am 93:2249-2254, 2011. http://dx.doi.org/10.2106/JBJS.J.01994. [PubMed PMID: 22258770] 9. Matsen 3rd FA, Butler-Wu S, Carofino BC, et al: Origin of Propionibacterium in surgical wounds and evidence-based approach for culturing Propionibacterium from surgical sites. J Bone Joint Surg Am 95: e1811-e1817, 2013. http://dx.doi.org/10.2106/JBJS.L.01733. [PubMed PMID: 24306704]
J.-W.K. Ko and S. Namdari 10. Lee MJ, Pottinger PS, Butler-Wu S, et al: Propionibacterium persists in the skin despite standard surgical preparation. J Bone Joint Surg Am 96:1447-1450, 2014. http://dx.doi.org/10.2106/JBJS.M.01474. [PubMed PMID: 25187583] 11. Matsen 3rd FA, Russ SM, Bertelsen A, et al: Propionibacterium can be isolated from deep cultures obtained at primary arthroplasty despite intravenous antimicrobial prophylaxis. J Shoulder Elbow Surg 24:844-847, 2015. http://dx.doi.org/10.1016/j.jse.2014.10.016. [Pub Med PMID: 25547858] 12. Maccioni CB, Woodbridge AB, Balestro JC: Low rate of Propionibacterium acnes in arthritic shoulders undergoing primary total shoulder replacement surgery using a strict specimen collection technique. J Shoulder Elbow Surg:. http://dx.doi.org/10.1016/j.jse.2014.12.026. [PubMed PMID: 25700640] 13. Levy O, Iyer S, Atoun E: Propionibacterium acnes: An underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg 22:505-511, 2013. http://dx.doi.org/10.1016/j.jse.2012.07.007. [Pub Med PMID: 22981447] 14. Pottinger P, Butler-Wu S, Neradilek MB: 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. J Bone Joint Surg Am 94:2075-2083, 2012. http://dx.doi.org/ 10.2106/JBJS.K.00861. [PubMed PMID: 23172325] 15. Singh JA, Sperling JW, Schleck C, et al: Periprosthetic infections after shoulder hemiarthroplasty. J Shoulder Elbow Surg 21:1304-1309, 2012. http://dx.doi.org/10.1016/j.jse.2011.08.067. [PubMed PMID: 22154310; PubMed Central PMCID: PMC3310339] 16. Cheung EV, Sperling JW, Cofield RH: Infection associated with hematoma formation after shoulder arthroplasty. Clin Orthop Relat Res 466:1363-1367, 2008. http://dx.doi.org/10.1007/s11999-008-0226-3. [PubMed PMID: 18421541; PubMed Central PMCID: PMC2384030] 17. Pochi PE, Strauss JS, Downing DT: Age-related changes in sebaceous gland activity. J Invest Dermatol 73:108-111, 1979. [PubMed PMID: 448169] 18. Zouboulis CC: Acne and sebaceous gland function. Clin Dermatol 22:360-366, 2004. http://dx.doi.org/10.1016/j.clindermatol.2004.03. 004. [PubMed PMID: 15556719] 19. Cheung E, Willis M, Walker M, et al: Complications in reverse total shoulder arthroplasty. J Am Acad Orthop Surg 19:439-449, 2011. [PubMed PMID: 21724923] 20. Dines JS, Fealy S, Strauss EJ: Outcomes analysis of revision total shoulder replacement. J Bone Joint Surg Am 88:1494-1500, 2006. http://dx.doi. org/10.2106/JBJS.D.02946. [PubMed PMID: 16818975] 21. Palestro CJ: Nuclear medicine and the failed joint replacement: Past, present, and future. World J Radiol 6:446-458, 2014. http://dx.doi.org/ 10.4329/wjr.v6.i7.446. [PubMed PMID: 25071885; PubMed Central PMCID: PMC4109096] 22. Topolski MS, Chin PY, Sperling JW, et al: Revision shoulder arthroplasty with positive intraoperative cultures: The value of preoperative studies and intraoperative histology. J Shoulder Elbow Surg 15:402-406, 2006. http://dx.doi.org/10.1016/j.jse.2005.10.001. [PubMed PMID: 16831641] 23. Millett PJ, Yen YM, Price CS, et al: Propionibacterium acnes infection as an occult cause of postoperative shoulder pain: A case series. Clin Orthop Relat Res 469:2824-2830, 2011. http://dx.doi.org/10.1007/s11999-0111767-4. [PubMed PMID: 21240577; PubMed Central PMCID: PMC 3171528] 24. Foruria AM, Fox TJ, Sperling JW, et al: Clinical meaning of unexpected positive cultures (UPC) in revision shoulder arthroplasty. J Shoulder Elbow Surg 22:620-627, 2013. http://dx.doi.org/10.1016/j.jse.2012.07. 017. [PubMed PMID: 22981448] 25. Parvizi J, Zmistowski B, Berbari EF: New definition for periprosthetic joint infection: From the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 469:2992-2994, 2011. http://dx.doi.org/10.1007/ s11999-011-2102-9. [PubMed PMID: 21938532; PubMed Central PMCID: PMC3183178] 26. Piper KE, Fernandez-Sampedro M, Steckelberg KE: C-reactive protein, erythrocyte sedimentation rate and orthopedic implant infection. PLoS One 5:e9358, 2010. http://dx.doi.org/10.1371/journal.pone.0009358. [PubMed PMID: 20179760; PubMed Central PMCID: PMC2825262]
The diagnosis and management of PJIs of the shoulder 27. Di Cesare PE, Chang E, Preston CF, et al: Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am 87:1921-1927, 2005. http://dx.doi.org/10.2106/JBJS. D.01803. [PubMed PMID: 16140805] 28. Grosso MJ, Frangiamore SJ, Saleh A, et al: Poor utility of serum interleukin-6 levels to predict indolent periprosthetic shoulder infections. J Shoulder Elbow Surg 23:1277-1281, 2014. http://dx.doi.org/10.1016/j. jse.2013.12.023. [PubMed PMID: 24725902] 29. Villacis D, Merriman JA, Yalamanchili R, et al: Serum interleukin-6 as a marker of periprosthetic shoulder infection. J Bone Joint Surg Am 96:41-45, 2014. http://dx.doi.org/10.2106/JBJS.L.01634. [PubMed PMID: 24382723] 30. Della Valle C, Parvizi J, Bauer TW: American Academy of Orthopaedic Surgeons clinical practice guideline onthe diagnosis of periprosthetic joint infections of the hip and knee. J Bone Joint Surg Am 93:1355-1357, 2011. http://dx.doi.org/10.2106/JBJS.9314ebo. [PubMed PMID: 21792503] 31. Della Valle C, Parvizi J, Bauer TW, et al: Diagnosis of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg 18:760-770, 2010. [PubMed PMID: 21119142] 32. Barrack RL, Jennings RW, Wolfe MW, et al: The Coventry Award. The value of preoperative aspiration before total knee revision. Clin Orthop Relat Res 345:8-16, 1997. [PubMed PMID: 9418615] 33. Dilisio MF, Miller LR, Warner JJ, et al: Arthroscopic tissue culture for the evaluation of periprosthetic shoulder infection. J Bone Joint Surg Am 96:1952-1958, 2014. http://dx.doi.org/10.2106/JBJS.M.01512. [PubMed PMID: 25471909] 34. Morman M, Fowler RL, Sanofsky B, et al: Arthroscopic tissue biopsy for evaluation of infection before revision arthroplasty. J Shoulder Elbow Surg 20:e15-e22, 2011. http://dx.doi.org/10.1016/j.jse.2010.11.015. [PubMed PMID: 21330156] 35. Parvizi J, Jacovides C, Antoci V, et al: Diagnosis of periprosthetic joint infection: The utility of a simple yet unappreciated enzyme. J Bone Joint Surg Am 93:2242-2248, 2011. http://dx.doi.org/10.2106/JBJS.J.01413. [PubMed PMID: 22258769] 36. Tischler EH, Cavanaugh PK, Parvizi J: Leukocyte esterase strip test: Matched for musculoskeletal infection society criteria. J Bone Joint Surg Am 96:1917-1920, 2014. http://dx.doi.org/10.2106/JBJS.M.01591. [PubMed PMID: 25410511] 37. Frangiamore SJ, Saleh A, Kovac MF, et al: Synovial fluid interleukin-6 as a predictor of periprosthetic shoulder infection. J Bone Joint Surg Am 97:63-70, 2015. http://dx.doi.org/10.2106/JBJS.N.00104. [PubMed PMID: 25568396] 38. Frangiamore SJ, Saleh A, Grosso MJ, et al: Alpha-defensin as a predictor of periprosthetic shoulder infection. J Shoulder Elbow Surg:. http://dx.doi. org/10.1016/j.jse.2014.12.021. [PubMed PMID: 25672257] 39. Kelly 2nd JD, Hobgood ER: Positive culture rate in revision shoulder arthroplasty. Clin Orthop Relat Res 467:2343-2348, 2009. http://dx.doi. org/10.1007/s11999-009-0875-x. [PubMed PMID: 19434469; PubMed Central PMCID: PMC2866925] 40. Della Valle CJ, Bogner E, Desai P, et al: Analysis of frozen sections of intraoperative specimens obtained at the time of reoperation after hip or knee resection arthroplasty for the treatment of infection. J Bone Joint Surg Am 81:684-689, 1999. [PubMed PMID: 10360696]
7 41. Lonner JH, Desai P, Dicesare PE, et al: The reliability of analysis of intraoperative frozen sections for identifying active infection during revision hip or knee arthroplasty. J Bone Joint Surg Am 78:1553-1558, 1996. [PubMed PMID: 8876584] 42. Grosso MJ, Frangiamore SJ, Ricchetti ET, et al: Sensitivity of frozen section histology for identifying Propionibacterium acnes infections in revision shoulder arthroplasty. J Bone Joint Surg Am 96:442-447, 2014. http://dx. doi.org/10.2106/JBJS.M.00258. [PubMed PMID: 24647499] 43. Lutz MF, Berthelot P, Fresard A, et al: Arthroplastic and osteosynthetic infections due to Propionibacterium acnes: A retrospective study of 52 cases, 1995-2002. Eur J Clin Microbiol Infect Dis 24:739-744, 2005. http: //dx.doi.org/10.1007/s10096-005-0040-8. [PubMed PMID: 16328558] 44. Grosso MJ, Sabesan VJ, Ho JC, et al: Reinfection rates after 1-stage revision shoulder arthroplasty for patients with unexpected positive intraoperative cultures. J Shoulder Elbow Surg 21:754-758, 2012. http://dx.doi.org/ 10.1016/j.jse.2011.08.052. [PubMed PMID: 22305921] 45. Crockarell JR, Hanssen AD, Osmon DR, et al: Treatment of infection with debridement and retention of the components following hip arthroplasty. J Bone Joint Surg Am 80:1306-1313, 1998. [PubMed PMID: 9759815] 46. Bradbury T, Fehring TK, Taunton M, et al: The fate of acute methicillinresistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. J Arthroplasty 24:101-104, 2009. http://dx.doi.org/10.1016/j.arth.2009.04.028 (suppl 6) [PubMed PMID: 19553077] 47. Schoifet SD, Morrey BF: Treatment of infection after total knee arthroplasty by debridement with retention of the components. J Bone Joint Surg Am 72:1383-1390, 1990. [PubMed PMID: 2229118] 48. Ince A, Seemann K, Frommelt L, et al: One-stage exchange shoulder arthroplasty for peri-prosthetic infection. J Bone Joint Surg Br 87: 814-818, 2005. http://dx.doi.org/10.1302/0301-620X.87B6.15920. [PubMed PMID: 15911665] 49. Coffey MJ, Ely EE, Crosby LA: Treatment of glenohumeral sepsis with a commercially produced antibiotic-impregnated cement spacer. J Shoulder Elbow Surg 19:868-873, 2010. http://dx.doi.org/10.1016/j.jse.2010.01. 012. [PubMed PMID: 20392651] 50. Strickland JP, Sperling JW, Cofield RH: The results of two-stage reimplantation for infected shoulder replacement. J Bone Joint Surg Br 90:460-465, 2008. http://dx.doi.org/10.1302/0301-620X.90B4.20002. [PubMed PMID: 18378920] 51. Weber P, Utzschneider S, Sadoghi P, et al: Management of the infected shoulder prosthesis: A retrospective analysis and review of the literature. Int Orthop 35:365-373, 2011. http://dx.doi.org/10.1007/s00264-0101019-3. [PubMed PMID: 20405287; PubMed Central PMCID: PMC 3047637] 52. Seitz Jr. WH, Damacen H: Staged exchange arthroplasty for shoulder sepsis. J Arthroplasty 17:36-40, 2002 (4 suppl 1) [PubMed PMID: 12068401] 53. Safran O, Iannotti JP: Arthrodesis of the shoulder. J Am Acad Orthop Surg 14:145-153, 2006. [PubMed PMID: 16520365] 54. Bilgin SS: Reconstruction of proximal humeral defects with shoulder arthrodesis using free vascularized fibular graft. J Bone Joint Surg Am 94: e94, 2012. http://dx.doi.org/10.2106/JBJS.J.01823. [PubMed PMID: 22760395]