Periprosthetic infection in shoulder and elbow joints

Periprosthetic infection in shoulder and elbow joints

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M.H. Amini*, P.J. Evans*, E.T. Ricchetti*,† * Cleveland Clinic, ​Orthopaedic and Rheumatologic Institute, Cleveland, OH, United States, †Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States

8.1 Introduction The incidence of upper extremity arthroplasty in the United States continues to rise, a trend that increases at a faster pace with time. Shoulder arthroplasty grows each year not only because of the continued growth of hemiarthroplasty and anatomic total shoulder arthroplasty (TSA) but also because of the rapid acceptance of the reverse total shoulder arthroplasty (RSA) and the evolution of its indications. The incidence rose 2.5 fold over a decade [1]. Similarly, the incidence of total elbow arthroplasty (TEA) grew 248% from 1993 to 2007, and the incidence of upper extremity revision arthroplasty grew 500% during the same time period [2]. This rise in surgical volume can lead to a similar rise in volume of surgical complications, including infection. In a systematic review of TSA, Bohsali et al. reported that infection affected 0.7% of all TSAs and that infection made up 4.6% of all complications [3]. More recently, Gonzalez et al. similarly reported an incidence of infection after TSA of 1.1%, which comprised 2.9% of all complications [4]. In 2011, median hospitalization costs for shoulder periprosthetic joint infections (PJI) were $17,163.57, a substantial burden to the healthcare system given the large volume of shoulder arthroplasties performed and the incidence of infection [5]. The risk of infection after TEA is substantially higher than the risk after shoulder arthroplasty, or even hip and knee arthroplasty. Earlier studies reported infection rates near 10%, though more recently this has been reported to be around 3% [6,7]. However, the rate of infection is higher in patients with rheumatoid arthritis at 5% [8,9], and in the revision setting at 8% [10]. Despite the growing incidence of shoulder and elbow arthroplasty, and the difficulty in treating infections in these joints, there is relatively little evidence to guide prognosis, diagnosis, and management in comparison to the large volume of high-quality evidence in the literature on infected hip and knee arthroplasty. Studies are often retrospective, with small case series of a single institution; therefore, results may not be generalizable. Further compounding these issues is the predominance of less virulent organisms in the shoulder and elbow, particularly Propionibacterium acnes (P. acnes) and coagulase-negative Staphylococcus, that may be less clinically evident and more difficult to diagnose, particularly in shoulder arthroplasty [11–13]. We will review the clinical presentation, diagnostic testing, and treatment and outcomes of infection after shoulder and elbow arthroplasty. Management of Periprosthetic Joint Infections (PJIs). http://dx.doi.org/10.1016/B978-0-08-100205-6.00008-2 © 2017 Elsevier Ltd. All rights reserved.

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8.2 Clinical presentation Infections in total joint arthroplasty are often classified by chronicity as acute (less than 3 months after surgery), subacute (3–12 months after surgery), and late/chronic (greater than 1 year after surgery) [3,14,15]. A slightly different classification in the hip and knee literature includes four types: type 1 (the presence of positive intraoperative cultures at revision surgery), type 2 (acute postoperative infection within 30 days of arthroplasty), type 3 (acute hematogenous infection occurring at any time), and type 4 (chronic infection) [16]. Infections caused by nonvirulent organisms, such as P. acnes, are typically present since the time of primary arthroplasty but are often chronic by the time of diagnosis, as the paucity of clinical signs of infection leads to a delay in diagnosis. As with any clinical evaluation, the workup should begin with a detailed history of the patient’s clinical course and symptoms after the index procedure. The surgeon should specifically ask about the recovery after the initial arthroplasty, whether there was a period of pain relief and functional gain followed by eventual decline or if the patient never experienced improvement in pain and/or motion, and whether there were any wound healing issues, prolonged drainage, or antibiotic use. Patients with infected shoulder arthroplasty typically present with pain as the primary complaint, frequently noting that the pain never went away postoperatively. While component loosening may cause pain with activity, patients with infection typically report rest pain and constant pain, though the pain may be worse with activity if the infection leads to early component loosening. Stiffness is also commonly reported in patients with infected shoulder arthroplasties [14,17]. They typically never regained full or adequate motion after the arthroplasty despite thorough rehabilitation. The stiffness is often associated with pain, which then further worsens the stiffness. Patients frequently do not have the typical signs of infection, including wound drainage, fevers, chills, etc., with infections caused by indolent organisms, such as P. acnes. A history of wound issues in the immediate postoperative period should be noted, however. A history of hematoma formation at the time of the arthroplasty, particularly one requiring reoperation, is associated with an increased risk of PJI [18]. The surgeon should carefully review the medical history and comorbidities, evaluating for risk factors for PJI. Intrinsic factors include diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, prior surgery, other sources of infection, malnutrition, obesity, and older age, while extrinsic factors include repeated steroid injections, oral corticosteroid use, chemotherapy, and local radiation [3,14,17,19,20]. The surgeon should examine the previous incision for healing, erythema, cellulitis, swelling, drainage, or a sinus tract. Sometimes P. acnes presents with a diffuse, nonblanching, erythematous rash about the incision; however, most shoulder arthroplasty infections have normal-appearing surgical incisions. Wound complications after elbow arthroplasty, however, are more frequent, particularly in those patients with a poor soft tissue envelope or in immunocompromised hosts. Jeon et al. noted a 5.5% rate (97 of 1749) of wound problems, including delayed healing and hematoma in 34 cases, and hematoma in 33, 9 of which progressed to infection. Of the 97 cases with wound problems, 24 progressed to a deep infection and 11 of them required resection arthroplasty [21]. Palpation of the joint line, along with other relevant structures, will help localize the pain and look for other sources of pain. Active and passive range of

Periprosthetic infection in shoulder and elbow joints159

motion are commonly restricted in all planes as a result of the scar tissue and ensuing stiffness that form because of an infection. Differences in active and passive motion or deficits in strength testing may suggest rotator cuff pathology in the shoulder or impairment of the biceps and triceps in the elbow. The clinician must also evaluate for other sources of pain and/or dysfunction, especially the cervical spine.

8.3 Diagnostic testing 8.3.1 General Working up a prosthetic shoulder or elbow joint for infection should begin with a detailed history and physical examination as outlined previously. Further diagnostic testing includes laboratory and imaging studies. Serum white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), radiographs, and joint aspiration are the most common first line tests [3,20]. Advanced imaging, such as CT, US, MRI, or indium In-111-labeled WBC scan may also be obtained. It is important to note that no single test is reliable enough by itself to diagnose PJI [22]. Though ESR and CRP are nonspecific inflammatory markers, they are often elevated in cases of PJI [14,17,23,24]. They both often remain elevated in the acute postoperative period and are less useful during this time, with CRP normalizing by roughly 2 weeks and ESR returning to normal over a more prolonged period [25–27]. It is important to consider that inflammatory conditions, such as rheumatoid arthritis, may elevate inflammatory markers, making the interpretation of ESR and/or CRP in the workup of possible PJI challenging in these patients. If a patient has baseline elevation of ESR and/or CRP from an inflammatory disease process, a further increase in these markers may be a sign of developing PJI. However, interpreting an elevation in this setting may still not always be straight forward, as fluctuations of ESR and/or CRP can occur as a part of the normal disease process for such inflammatory conditions. Aspiration of synovial fluid from the prosthetic joint can be extremely helpful in the diagnostic work-up. This can often be done in the office, blindly or with US-guidance, or if unsuccessful, this can be performed fluoroscopically by a radiologist to ensure that the needle is within the joint. As with any other aspiration, the needle should not be placed through any areas of cellulitis. Patients should be off antibiotics for at least 2 weeks prior to the aspiration to maximize the yield of the synovial culture [22]. Synovial WBC count and WBC differential have been well reported in the hip and knee literature, and well-­ established guidelines exist in the diagnosis of hip and knee PJI. Combining the synovial WBC count and differential with ESR and CRP also improves the ability to diagnose a hip or knee PJI [22]. However, in the upper extremity, established cutoff levels do not exist. Radiographs should be carefully examined for new or progressive radiolucencies, or gross loosening of one or both components. Particularly if there is no identifiable cause for early progressive radiolucencies or loosening, the clinician should have a high index of suspicion for PJI. In addition to lucencies, periosteal new bone formation may suggest a PJI [26]. Technetium Tc-99 bone scan and indium In-111-labeled WBC scan largely play a limited role in the work-up of PJI, though they may be helpful if other testing has been equivocal [22].

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For those scheduled to undergo revision surgery, particularly if the work-up was negative but the suspicion for PJI remains, the patient should again be off antibiotics for at least 2 weeks prior to surgery, and intraoperative cultures and pathologic specimens, including frozen sections, should be obtained. The surgeon should obtain samples from the joint capsule/synovial lining, the prosthesis-bone interface, and the medullary canal(s) to adequately sample all potential niduses for infection. Intraoperative frozen sections are often the only point-of-care test available to the surgeon in the operating room. Generally, five or more polymorphonuclear (PMN) leukocytes per high-powered field are considered positive for infection, based on literature from hip and knee arthroplasty [15,23,26,28–30]. Intraoperative gram stain is no longer obtained because of its poor utility and because it has been reported negative in cases of confirmed infection. Even cultures have been reported to be negative in the same scenario. This may be because of insufficient tissue samples, inadequate culture length, or failing to discontinue antibiotics early enough before the operation [14,15,17,31]. Because of the prevalence of slow-growing, low-virulence organisms in upper extremity PJI, cultures should often be held for more prolonged periods of time than usual. We will discuss this in more detail in the following sections.

8.3.2 Shoulder specific Because of the indolent nature of many of the offending organisms in PJIs of the shoulder, many of the typical diagnostic tests may be negative. Villacis et al., in a study of 14 infected shoulder arthroplasties in 34 patients, evaluated the utility of common serum markers and noted poor sensitivity for all. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for WBC were 7%, 95%, 50%, 59%, and 59%, for ESR were 21%, 65%, 30%, 54%, and 47%, and for CRP were 0%, 95%, 0%, 57%, and 56% [32]. Another recent prospective study of 24 infections in 69 patients undergoing revision shoulder arthroplasty by Grosso et al. showed a sensitivity and specificity for ESR of 42% and 82%, and for CRP of 46% and 93% [33]. Piper et al. showed in a systematic review that ESR and CRP have sensitivities of 16% and 42% in shoulder PJIs compared to 75% and 88% in hip and knee PJIs [34]. Serum interleukin-6 (IL-6) has received attention in hip and knee PJI due to increased sensitivity and specificity in diagnosis of PJI [35] and has subsequently been evaluated in the shoulder, as well. The study by Villacis et al. also prospectively evaluated the utility of IL-6 and showed that there was no difference in IL-6 levels between infected and noninfected shoulder arthroplasties, and that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 14%, 95%, 67%, 61%, and 62%, respectively [32]. Similarly, in the study by Grosso et al., the sensitivity was 12% and the specificity was 93%, making it less sensitive than ESR and CRP (42% and 46%, respectively) in that series [33]. Aspiration is an important part of the diagnostic workup in possibly infected shoulder arthroplasties. But again, the indolent nature of many shoulder PJIs leads to a decreased synovial inflammatory response and decreased synovial fluid production relative to infected hip and knee arthroplasties. Frequently, attempts at aspiration are unsuccessful. Sperling et al. noted that aspiration was successful in only 56% of patients who were later confirmed to have a PJI, the majority of which were coagulase-negative

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Staphylococcus or P. acnes [14]. Codd et al. noted that aspiration was successful in only 38.8% of shoulder arthroplasties, and a pathogen was isolated in only 29% [36]. Dilisio et al. recently evaluated fluoroscopically guided aspiration of 19 painful arthroplasties that later went on to revision and found a sensitivity, specificity, positive, and negative predictive values of 16.7%, 100%, 100%, and 58.3% [37]. Even when successful, the volume of aspirate can be limited and may preclude testing of synovial WBC count and differential. As a result, shoulder-specific cutoff values have not been reported. In addition to sending the fluid for aerobic and anaerobic cultures, some newer tests examining synovial fluid biomarkers have shown promise in the detection of prosthetic infection. Synovial IL-6 was prospectively evaluated by Frangiamore et al. in a study of 35 painful shoulder arthroplasties undergoing revision surgery. Using receiver operating characteristic curve analysis, a cutoff value of 359.3 pg/mL led to sensitivity, specificity, positive, and negative likelihood ratios of 87%, 90%, 8.45, and 0.15. Seven patients with negative preoperative workup were later diagnosed with infection based on multiple positive intraoperative cultures, and the synovial IL-6 level was elevated in five of them, with a mean level of 1400 pg/mL. Levels were also significantly elevated in patients with P. acnes infections [38]. In a similarly modeled study, Frangiamore et al. evaluated synovial α-defensin in 33 painful shoulder arthroplasties undergoing revision surgery. Sensitivity, specificity, positive, and negative likelihood ratios were 63%, 95%, 12.1, and 0.38, and α-defensin was significantly elevated in the presence of a culture positive for P. acnes and moderately correlated with the number of positive intraoperative cultures [39]. Nearly all culture-positive cases in these two studies were P. acnes or coagulase-negative Staphylococcus. Leukocyte esterase is another synovial fluid analysis that has been evaluated in shoulder arthroplasty after showing promising results in hip and knee PJI [40,41]. However, Nelson et al. evaluated 85 primary and revision arthroplasties, including 10 infected revisions, and showed sensitivity, specificity, positive, and negative predictive values of only 30%, 67%, 43%, and 83%. It is important to note that aspirates that contain blood must be centrifuged prior to testing, and 29% of the time, even after centrifuging, the aspirate was too bloody for analysis [42]. If workup of a painful shoulder arthroplasty is negative for infection, but there is no other indication for revision surgery and the concern for PJI remains high, arthroscopic tissue biopsy may be considered. Multiple tissue samples can be taken from around the components as well as from the joint capsule, and other cause of pain can also be evaluated, including component loosening and rotator cuff deficiency. The recent study by Dilisio et al. retrospectively evaluated 19 patients with painful arthroplasties who underwent arthroscopic biopsy prior to revision surgery, 7 (41%) of which later grew P. acnes. The sensitivity, specificity, positive, and negative predictive values were all 100%, and all arthroscopic cultures matched cultures taken during the revision surgery [37]. Preoperative workup can often be equivocal, leaving the surgeon to rely on intraoperative findings and testing if revision surgery is performed. Gram staining has previously been a mainstay of point-of-care testing for infection, but because of poor sensitivity noted in the hip and knee literature, is no longer recommended [22,43–45]. In a known infection, however, intraoperative gram stain may guide immediate empiric antibiotic coverage. Frozen section histology has also been evaluated in shoulder arthroplasty. One study noted a 92% rate of negative intraoperative frozen sections

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in patients later confirmed with culture-positive infection, and another showed no correlation between frozen sections and positive cultures, with the exception of Staphylococcus aureus [30]. However, recent data suggest that the use of alternate criteria for intraoperative frozen section analysis may improve the ability to detect P. acnes infections in the shoulder. Grosso et al. evaluated 45 patients who underwent frozen section histology during revision shoulder arthroplasty, including 18 P. acnes infections and 12 infections from other organisms. Using a standard threshold of 5 PMN cells per high-power field (400×), the sensitivity was 50% for P. acnes infections and 67% for other infections, while the specificity was 100%. Using a new threshold of 10 PMNs in each of the 5 densest high-power fields, the sensitivity for P. acnes infections improved to 72%, while the specificity remained 100% [46]. Implant sonication is another method that may improve the ability to detect organisms of low virulence. Ultrasonic pressure waves dislodge biofilms from the surface of the implant to increase the sensitivity of detection. Piper et al. showed that sonication improves the sensitivity from 54.5% to 66.7%. However, the workflow and coordination necessary to transmit large, sterile containers for holding the components have limited the widespread use of this technique [12]. Despite advances in the preoperative and intraoperative diagnosis of shoulder PJI, the possibility of an unexpected positive culture remains, and the surgeon may have to rely on other signs to guide intraoperative decision-making. In a study of 193 apparently aseptic revision shoulder arthroplasties, male sex, humeral loosening, membrane formation, and cloudy fluid were independent predictors of postoperative positive culture growth for P. acnes. In this study, the rate of unexpected positive cultures was 56% [47]. Another study from the same institution compared P. acnes positive revision arthroplasties to aseptic revisions and noted that the P. acnes positive patients were more likely to be male; have glenoid erosions, osteolysis, or loosening; and have a humeral membrane [48]. Several other studies have reported lower rates of unexpected positive cultures. In a cohort of 148 apparently aseptic revisions performed 3 years or more after primary arthroplasty, the rate of positive cultures was 9.5% [49]. Another study noted a rate of 15% in a similar cohort of apparently aseptic revision arthroplasties, and of these, only 10% resulted in a symptomatic infection [50]. Grosso et al. found that only 5.9% of patients with unexpected positive cultures experienced a symptomatic infection [51]. Prolonged postoperative antibiotic therapy may not be necessary for patients with unexpected positive cultures, particularly if all previous hardware was removed and antibiotic cement was used at the time of revision, but further data are needed to confirm this.

8.3.3  Propionibacterium acnes P. acnes is a relatively slow-growing organism that can be difficult to isolate in routine cultures with standard incubation periods and can remain in the soft tissues even after adequate antisepsis. Lee et al. showed that after skin preparation with ChloroPrep (CareFusion, San Diego, California) that punch biopsies of 7 of 10 male volunteers were culture positive for P. acnes [52]. Matsen et al. showed that 3 of 10 male patients had P. acnes growth from deep tissues during primary arthroplasty after skin

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p­ reparation and intravenous antibiotics [53]. In a study of revision arthroplasties from the same authors, P. acnes grew from dermal specimens in 12 of 21 males and 0 of 20 females, and deep specimens grew from 12 of 20 males and 1 of 20 females [54]. Many have recognized the need to incubate cultures for longer than standard incubation times of five days in order to improve the ability to isolate P. acnes. Some studies recommend incubation periods of up to 21–28 days [55–57]. However, the clinical relevance and the risk of reinfection in those with late culture growth remain unknown. Butler-Wu et al. recommended holding cultures for 13 days, as those that grew after this point were considered to be contaminants. They also noted that holding only the anaerobic cultures for prolonged incubation periods would have missed 29.4% of P. acnes isolates and suggest holding both aerobic and anaerobic cultures for this time frame [58]. We routinely obtain three to five specimens for culture during revision shoulder arthroplasty from different locations—capsule, periprosthetic humeral and glenoid tissue—­and hold each for aerobic and anaerobic culture for a period of 14 days. P. acnes positive cultures have been reported in several recent studies in patients undergoing first time open shoulder surgery. Levy et al. cultured aspirates and specimens in 55 consecutive patients undergoing primary shoulder arthroplasty and noted that 41.8% of patients were culture positive for P. acnes. No patient developed a postoperative infection, though the authors treated culture-positive patients with 4 weeks of oral antibiotics and also suggested that P. acnes may be implicated as a possible cause for glenohumeral osteoarthritis based on the high positive culture rate [59]. However, other recent studies using strict specimen collection protocols and/or control specimens suggest that P. acnes positive cultures during first time shoulder surgery may more likely represent contaminants rather than true positive results. Maccioni et al. utilized a strict specimen collection protocol in 32 patients undergoing primary shoulder arthroplasty in which 5 capsule/synovium specimens were sent for culture and a sixth was sent for histopathology and noted that only 3 patients (9.4%) grew P. acnes, with only 1 showing growth on more than 1 specimen. Histopathology was negative for infection in all positive culture cases [60]. Mook and Garrigues also recently reported a 17.1% (14/82) rate of positive P. acnes culture in patients undergoing first time open shoulder surgery, with most cases representing an isolated result (three capsule specimens taken per case) that grew out late. In addition, a sterile gauze sponge was sent as a control culture specimen in all of the prospectively enrolled patients in the study and had a 13.0% (7/54) rate of positive culture (5/7 positive cultures grew P. acnes). Taken together, these studies suggest a significant contamination rate with P. acnes positive cultures, likely due to the increased incubation times for these specimens and the increased handling of samples as a result of the longer culture times [61]. In the setting of revision shoulder arthroplasty, interpretation of a positive P. acnes culture result should be made in the context of the overall clinical picture. This should take into account other positive preoperative and intraoperative markers for infection, including traditional serum markers and intraoperative frozen section findings, as well as newer synovial fluid biomarkers, if available, and the characteristics of the positive culture result(s) themselves, such as the timing of the first positive culture and the number of positive culture results relative to the overall number of cultures taken. Such data taken together can help determine whether a positive culture is likely to represent

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a false positive result consistent with contamination or a true positive finding. A recent study by Frangiamore et al. highlights this approach. In 46 patients who underwent revision shoulder arthroplasty and had at least one positive P. acnes culture, cases were classified into one of two groups based on culture results and other perioperative findings of infection, a probable true positive culture group and a probable contaminant group. Time to P. acnes growth in culture was found to be significantly shorter in the probable true positive culture group compared with the probable contaminant group (median of 5 days compared with 9 days). There were also significantly fewer days to P. acnes culture growth among cases with a higher number of positive cultures and a higher proportion of positive cultures, regardless of group classification [38,39,62].

8.3.4 Elbow specific Workup should begin with routine blood tests as in any other possibly infected arthroplasty, including ESR, CRP, and WBC count and differential. However, there is little literature on the utility of these tests in PJI of the elbow, and a large number of patients with TEAs have inflammatory arthritis, limiting the use of inflammatory markers in these patients. Mean ESR in infected TEA has been reported between 30 and 55 mm/h [7,63,64]. Because of the lack of information to guide the use of serum markers, aspiration and culture remains the main diagnostic test to augment clinical suspicion of infection in the elbow. Similar to the shoulder, we recommend the surgeon should obtain three to five specimens for culture and intraoperative frozen section histology. Ahmadi et al. evaluated 227 revision TEAs and noted a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 51.3%, 93.1%, 60.6%, 90.2%, and 85.9% with frozen section histology [65]. As a result, negative frozen section histology does not exclude an infection, but a positive result is highly suggestive of one. Implant sonication has been evaluated in the diagnosis of an infection. Vergidis et al. reported on a series of 36 patients, including 9 infections, and noted a sensitivity and specificity of 89% and 100% compared to 55% and 93% for standard tissue culture [66]. However, because of limitations previously noted, it is not commonly used. Just as in the evaluation of a possibly infected shoulder arthroplasty, the perioperative workup may be completely negative in elbow PJI with indolent organisms, but intraoperative cultures may later become positive. Wee et al. evaluated 213 apparently aseptic revision TEAs and noted unexpected positive cultures in 7.5%. One patient was treated for infection because of early loosening, and nine of ten remained infection free at more than 2 years. One patient sustained an infection with a different organism [67].

8.4 Treatment and outcomes—Shoulder Treatment of shoulder PJI includes several surgical and nonsurgical options and can and should be tailored to each patient's specific clinical scenario, including the virulence and chronicity of infection, the stability of the implants, the quality of the soft tissues, the remaining bone stock and quality, and the patient's physiologic and psychological

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preparedness to undergo two-stage revision surgery if necessary. Treatment options include antibiotic suppression, irrigation and debridement with implant retention, resection arthroplasty, permanent antibiotic cement spacer placement, one-stage exchange with the use of antibiotic-impregnated cement, two-stage exchange with a temporary antibiotic cement spacer, arthrodesis, or amputation. Regardless of the method of treatment, care should include medical management of the infection with a peripherally inserted central catheter (PICC) line to receive organism-specific IV antibiotics typically for 6 weeks [68]. In patients too medically infirm to undergo surgical treatment of a PJI, or in patients who are unwilling to undergo surgical treatment, long-term antibiotic suppression is an option. This is particularly true if the patient has minimal to no symptoms, is not septic, and has a low-virulence organism. One small series noted a recurrence rate of 60% in shoulder arthroplasty [17]. Other series in knee arthroplasty note rates as low as 24% [69]. Implant retention with irrigation and debridement is most appropriate for acute postoperative infections (type 2) and acute hematogenous infections (type 3). Modular component exchange can be performed as part of the procedure, such as exchange of the modular head component in standard shoulder arthroplasty and exchange of the glenosphere and polyethylene liner in RSA. Modular component exchange also significantly facilitates exposure of the joint for thorough debridement, as much of the posterior joint would be inaccessible with component retention. Postoperatively, the patient receives 4–6 weeks of intravenous antibiotics, potentially followed by a period of oral antibiotic suppression. Most commonly, treatment of a shoulder PJI includes removal of the infected implant, particularly in chronic infections (type 4), in cases with highly virulent organisms, or in cases that have previously failed less aggressive surgical treatments. Removal of the implant should also include thorough bone and soft tissue debridement and removal of all cement [23,24,70–73]. The surgeon may need fluoroscopy to guide implant and cement removal, and a multitude of instruments should be available, including osteotomes, curettes, reamers, and a saw. A longitudinal unicortical osteotomy made the length of the stem and lateral to the bicipital groove may minimize the risk of unintended humeral fracture during implant removal [74]. The split can be gently hinged open to loosen the stem and remove cement, or if needed, the split can be converted to a cortical window and secured back at the end of the case with a monofilament cerclage wire or suture. As mentioned previously, three to five culture specimens should be obtained from the joint capsule and periprosthetic tissue of the humeral canal and the glenoid vault. Following implant removal, resection arthroplasty is an option in those with intractable infections, medical illnesses that preclude multiple operations, or soft tissue, bony, or neurologic deficits that preclude reimplantation of a new prosthesis (Fig. 8.1). Typically, resection arthroplasty provides good pain relief but leaves the patient with significant functional limitations. Sperling et al. noted that 11 patients all had moderate to complete pain relief, however, surgery was graded as successful in only three patients because of functional limitations, with mean abduction of 69 degrees and external rotation of 31 degrees [14]. Braman et al. followed seven patients

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Fig. 8.1  Anteroposterior radiograph demonstrating a resection arthroplasty of the shoulder for infection.

with resection arthroplasty and reported that all patients were satisfied, though none were considered satisfactory by Neer's criteria. All were able to perform activities of daily living (ADLs), but mean flexion was 28 degrees and mean external rotation was 8 degrees [75]. Rispoli followed 18 patients with resection arthroplasty (13 for infected arthroplasty) and reported significant pain relief in all, though five still had moderate to severe pain. Patients had significant functional limitations, with mean elevation of 70 degrees and mean external rotation of 31 degrees, simple shoulder test (SST) score of 3.1, and American Shoulder and Elbow Surgeons (ASES) score of 36 [76]. Muh et al. followed 26 patients and reported significant improvements in visual analog scale pain scores, with mean flexion of 45 degrees and mean external rotation of 9 degrees, and Constant scores of 27.3 [77]. Permanent placement of an antibiotic cement spacer can be performed for the same indications as resection arthroplasty, specifically those with contraindications to multiple surgical interventions (Fig. 8.2). Additionally, patients may be satisfied with the pain relief and function of a spacer initially placed as part of a two-stage protocol and may not wish to undergo reimplantation. A study of nine patients with antibiotic spacers who elected not to undergo reimplantation because of satisfaction with the spacer reported satisfaction in all nine patients, no or mild pain, and adequate performance of

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Fig. 8.2  Articulating antibiotic-impregnated cement spacer made with a prefabricated mold.

ADLs. Mean abduction was 75 degrees, mean external rotation was 25 degrees, and QDASH scores were 37.5 [78]. Reimplantation of a prosthesis typically provides the best functional outcome and can be done in one or two stages. One-stage exchange, with placement of a new prosthesis at the same time as the debridement and removal of the infected prosthesis, should be performed with antibiotic-impregnated cement. This approach may not be adequate in cases of highly resistant or highly virulent infections. Ince et al. studied 16 one-stage exchanges (15 to hemiarthroplasty, 1 to RSA) treated with antibiotics until the CRP was trending down, a mean of 8.6 days. There were no recurrent infections, mean abduction was 51.6 degrees, mean Constant scores were 33.6, and mean UCLA scores were 18.3 [79]. Beekman also reported on 11 patients, all of whom were revised to an RSA with antibiotic-impregnated cement and all of whom received at least 3 weeks of antibiotic therapy. There was one recurrent infection, and mean Constant scores were 55 [80]. Klatte et al. evaluated 35 patients treated with single-stage revision to various implants and a mean of 10.6 days of antibiotics. Two patients (5.7%) developed recurrent infection and were treated with resection arthroplasty. Mean Constant scores were 43.3 for hemiarthroplasties, 56.0 for bipolar hemiarthroplasties, and 61 for RSAs [81]. Two-stage exchange involves placement of an antibiotic-impregnated cement spacer followed by delayed reimplantation (Fig. 8.3). The cement spacer delivers a high concentration of antibiotics locally, minimizes soft tissue contractures by maintaining some soft tissue length, and maintains a space for future implant placement. Cement spacers can be made by hand or by a prefabricated mold. Prior to reimplantation, the surgeon should confirm that the infection has been cleared. At least 2 weeks after completion of a 6-week course of IV antibiotics, a new serum WBC, ESR, CRP,

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Fig. 8.3  Infected anatomic total shoulder arthroplasty. (A and B) Anteroposterior (AP) and lateral radiograph demonstrating loose glenoid and humeral components. Note the lucencies around the central glenoid peg (black arrow) and the endosteal erosion at the tip of the humeral stem (white arrows).

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Fig. 8.3 Continued.  (C) AP radiograph after removal of the prostheses and cement, and placement of a hand-molded antibiotic-impregnated cement spacer. (D) AP radiograph after revision to a reverse shoulder arthroplasty with a long humeral stem to bypass the endosteal erosion and cancellous allograft to fill the cavitary defects in the glenoid.

and glenohumeral aspiration should be obtained to ensure that serum tests have normalized and that the aspiration is culture negative [73]. If the infection clears after the initial debridement and antibiotic course, reimplantation is performed typically three months later. A computed tomography (CT) scan before reimplantation is helpful to better evaluate glenoid bone loss and morphology. At the time of the reimplantation,

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the surgeon should obtain multiple specimens for culture and pathology, as outlined previously. If there is still evidence of infection preoperatively or intraoperatively, the surgeon should perform a repeat surgical debridement and should place a new antibiotic spacer. Recently, Zhang et al. reported on 18 patients who underwent open biopsy before reimplantation and noted evidence of persistent infection in 22% of patients, and in 38% of patients with P. acnes. These patients underwent repeat debridements and further antibiotic therapy before final reimplantation [82]. Seitz and Damacen first reported on eight patients with infected shoulders (five shoulder arthroplasties) treated with two-stage exchange 6 months apart with 3 months of IV antibiotics. There were no recurrent infections, all patients noted improved pain and function, and mean Penn Shoulder scores were 68.4, though patients had decreased motion and strength compared to their contralateral shoulder [72]. Strickland et al. followed 19 patients who underwent 4–6 weeks of IV antibiotics and reimplantation at 11 weeks and noted that 7 of 19 had recurrent infections based on need for suppressive antibiotics in 6 and a subsequent resection arthroplasty in 1. Pain improved significantly, but outcomes were rated unsatisfactory in 68%, and there were 14 complications in the study group. Mean elevation was 89 degrees, mean external rotation was 43 degrees, and internal rotation was to L5 [15]. Hattrup and Renfree reported on 25 infected shoulders (20 arthroplasties) treated with 6 weeks of IV antibiotics and subsequent reimplantation. There were 3 recurrent infections, mean flexion was 100.9 degrees, abduction was 93.6 degrees, and external rotation was 32.6 degrees [83]. Coffey et al. treated 16 shoulders (11 arthroplasties) with a commercially produced cement spacer, IV antibiotics for 5.6 weeks, and reimplantation at 11.2 weeks. Four patients refused reimplantation because of satisfaction, and one underwent arthrodesis because of deltoid deficiency. There were no recurrent infections, and pain improved in all. Mean flexion was 110 degrees, mean external rotation was 20 degrees, UCLA scores were 26, SST scores were 6.6, ASES scores were 74, and Constant scores were 57 [84]. Sabesan et al. evaluated 17 patients treated with two-stage exchange, 6.3 weeks of IV antibiotics, and revision to RSA at 4.0 months. There was one recurrent infection, and seven complications, including the one recurrence, one hematoma, and five patients with instability. Mean flexion was 123 degrees, mean external rotation was 26 degrees, and Penn Shoulder scores were 66.4 [24]. Several studies have directly compared the previously mentioned treatment methods. Verhelst et al. evaluated 11 patients treated with resection arthroplasty and 10 patients with permanent spacers and noted no difference in recurrence rate or functional outcomes [85]. Codd et al. compared resection arthroplasty in five patients to reimplantation in 13 patients. Pain relief was similar in the two groups, though elevation was 66 degrees compared to 117 degrees, external rotation was 27 degrees compared to 38 degrees, and internal rotation was to the sacrum compared to L2 [36]. Stine compared permanent spacers to two-stage exchange in 30 patients. There were no recurrent infections and no differences in functional outcomes [73]. Cuff et al. compared one-stage exchange in 10 patients to two-stage exchange in 12 patients. There were no recurrent infections and no differences in functional outcomes between groups; however, there were 11 complications in 7 shoulders [23].

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Several studies have evaluated outcomes in case with unexpected positive culture results. Topolski et al. reported on 75 cases of revision arthroplasty with unexpected positive cultures. Fifty-four of 75 were treated with standard postoperative antibiotics. Ten patients underwent a second revision surgery, only one of which was for a documented recurrent infection, though 7 of the 10 had positive cultures at the time of the second revision [30]. Kelly and Hobgood evaluated eight patients with unexpected positive cultures and noted that two of eight developed a late infection. They recommended placing all revisions on oral antibiotics until cultures are negative and that culture-positive patients should be treated with 6 weeks of IV antibiotics [28]. We similarly reviewed 17 patients with unexpected positive cultures who were not treated with prolonged antibiotic therapy and noted recurrent infection in 1 of 17. There was no difference in recurrence rate or functional outcomes in these patients compared to one- and two-stage revisions for infection from our institution [51]. In the largest and most recent of these series, Foruria et al. evaluated the results of 107 consecutive cases of revision shoulder arthroplasty without preoperative or intraoperative signs of infection that were found to have at least one positive intraoperative culture. Sixtyeight (64%) of the cases grew P. acnes. Following one-stage revision, 53 cases were treated with an extended course of antibiotics, while 54 were not. At mean follow-up of 5.6 years, 11/107 (10%) cases had a subsequent positive culture result either by aspirate or during a second revision surgery that matched the culture result of the original revision surgery. Ten of the cases were P. acnes positive. Treatment with antibiotics did not appear to lower the risk of having a second positive culture result [50]. Dodson et al. reported on 11 patients with P. acnes infections, all of whom received prolonged antibiotic treatment. In five patients diagnosed preoperatively and treated with twostage exchange, there were two recurrent infections. Six patients were diagnosed with unexpected positive cultures, though the recurrence rate was not reported [86]. Arthrodesis is an option in those with axillary nerve or brachial plexus injuries, or combined loss of the rotator cuff and deltoid. Functional outcome is typically better than resection arthroplasty as it provides a stable platform for distal function; however, it is a technically demanding procedure given the bone loss typically present after implant removal. Scalise and Iannotti reported on a series of seven patients who underwent arthrodeses after failed arthroplasty and noted the need for a vascularized fibula in three patients and subsequent operations to obtain union in four [87]. As the above information shows, most studies on outcomes of treatment for infected shoulder arthroplasty report results on only a small number of patients, often with varying treatment protocols. This lack of uniformity in treatment approach, as well as in reported outcome measures, makes it difficult to draw definitive conclusions on specific treatment methods. As the most common clinical scenario in shoulder PJI is a chronic infection involving an indolent organism, further data are particularly needed to better define the indications and outcomes in cases of one- and two-stage exchange. Improved diagnostic testing to better identify P. acnes and other less virulent organisms preoperatively or intraoperatively may help more clearly define indications for one- versus two-stage exchange, as well as the need for postoperative antibiotic therapy in the setting of a presumed aseptic one-stage revision with unexpected positive culture results. Currently, our preferred management approach for a chronic PJI

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of the shoulder is a two-stage reimplantation when one or more perioperative signs of infection are present. We also routinely maintain all presumed aseptic revision shoulder arthroplasty cases on oral antibiotics postoperatively until all cultures are negative, due to the possibility of an unexpected positive culture. In this scenario, cases found to have multiple positive intraoperative cultures are treated with 6 weeks of IV antibiotic therapy, with transition to a more extended course of oral antibiotics based on the clinical presentation. If only one intraoperative culture turns positive, no further antibiotic therapy may be needed if the clinical picture is suggestive of a probable contaminant result. This is particularly true if the culture growth is late and all prior components were removed at revision surgery; however, retention of some of the prior components may still be an indication for postoperative antibiotic treatment.

8.5 Treatment and outcomes—Elbow Choosing a method of treatment for infected elbow arthroplasty depends on patientand disease-specific factors. The surgeon must consider the duration of symptoms, component fixation, quality of the soft tissue envelope, virulence of the infection, and the patient's health status and comorbidities. Treatment options include long-term antibiotic suppression, irrigation and debridement with implant retention, resection arthroplasty, one- and two-stage exchange, and arthrodesis. Regardless of the method chosen, the patient should receive a PICC line and organism-specific IV antibiotics. Long-term antibiotic suppression should be reserved for patients unwilling or unable to undergo operative treatment because of end-stage comorbidities. Patients should be appropriately counseled on the risk of continued or recurrent infection, though the exact rate remains unknown. Irrigation and debridement with component retention is best suited for acute postoperative and acute hematogenous infections with stable components. After exposure of the joint and prosthesis, the components are disarticulated and the bushings are removed. If the components are stable, the joint is thoroughly debrided and irrigated. If repeat debridements are deemed necessary, antibiotic-impregnated cement beads are placed in the joint and removed at the final debridement. Early studies reported poor success rates. Wolfe et al. reported on 11 patients treated with component retention and noted eight failures and intermittent drainage in the remaining three [64]. Cheung et al. reported on nine patients with success in only one of them [88]. Another study used this treatment in infections with durations of 30 days or less and noted a 50% success rate. Of note, all four patients with Staphylococcus epidermidis failed treatment, while six of eight with S. aureus were treated successfully [7]. Resection arthroplasty is a common treatment method for infected TEA. In the appropriately selected patient, pain relief and satisfaction are high, though functional limitations may persist. Those who are unfit or unwilling to undergo multiple operations and exchange arthroplasty, and those with limited functional demands are ideal candidates. The old components and cement mantle should be completely removed with attention to preserving the remaining bone stock. A unicortical osteotomy or ­cortical

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window may be necessary on the humeral and/or ulnar side to prevent accidental fracture during implant and cement removal. Any split or window is then repaired with monofilament cerclage wire or suture. Preservation of both condyles and deepening of the intervening sulcus are necessary to contain the ulna and provide a fulcrum for flexion and extension with a resection arthroplasty. Loss of one or both condyles or significant shortening results in worse functional outcomes [88]. The arm is placed in a cast for three to 4 weeks to obtain soft tissue stability. A hinged elbow brace can be used if there is significant instability. Zarkadas et al. reported on 30 resection arthroplasties with significant pain relief, and eight good results, eleven fair results, and eleven poor results. There were postoperative infections in 47%, intraoperative fractures in 35%, and permanent injury in 18% [89]. There is limited information on the success of one-stage exchange for an infected TEA. The surgeon should perform a thorough debridement of the bone and soft tissues, in addition to complete removal of the components and previous cement mantle. If a unicortical osteotomy or cortical window is necessary for component and cement removal, the new stem should bypass it by two cortical diameters. New components should be cemented with antibiotic-impregnated cement. One small series reported successful treatment in five of six patients with S. aureus infections [90]. Two-stage exchange is more commonly used than one-stage exchange for the treatment of infected TEA, particularly if the patient is medically fit to undergo two-stage reimplantation. As in one-stage exchange, the soft tissues should be thoroughly debrided, and the previous components and cement mantle should be carefully removed to prevent further bone loss. The condyles should be preserved in case the final result becomes a resection arthroplasty. Yamaguchi et al. reported an 80% success rate and noted that S. epidermidis was a significant risk for failure [7]. Peach et al. reported on a series of 34 infected TEAs that were to undergo two-stage exchange. Of these, 21% refused further surgery because of satisfaction with the resection, one patient did not clear the infection, and 76% underwent reimplantation. In those undergoing reimplantation, the recurrence rate was 11.5%, and mean Mayo elbow performance scores (MEPS) were 81.1 [91]. Cheung et al. reported on reimplantation of a TEA at a mean of 72.5 weeks after resection arthroplasty with a success rate of 72%. There were 52% good to excellent results, 10% fair, 38% poor, and mean MEPS of 66.3. Similar to other reports, S. epidermidis was associated with a higher risk of failure [92]. Arthrodesis has been reported in one series by Otto et al., who noted high complication rates and poor success in achieving a fusion. Of five patients, none had complete union, and two had fibrous unions. All patients underwent at least one reoperation, three required revision fixation for hardware failure, and two ultimately underwent resection arthroplasty. As a result, elbow arthrodesis is not recommended in the treatment of infected TEA [93]. Bone loss on the humeral and/or ulnar sides is a difficult problem when dealing with reconstructive efforts in the elbow, and use of allograft-prosthetic composites (APCs) and/or megaprostheses may be required. Morrey et al. reported on 25 patients treated with APCs and noted successful union in 92%. Of the seven patients in the series treated for infected TEAs, five were successfully salvaged with APCs [94].

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The extensor mechanism requires special attention in the multiply operated elbow. Duquin et al. importantly noted triceps weakness in 55% of patients after revision surgery for infected TEA, triceps or olecranon deficiency in 41%, and an intact extensor mechanism in only 11% [95]. Patients should be counseled on the risk of triceps insufficiency and wound breakdown because of the frequent need for reoperation and revision arthroplasty, often with allograft that may compromise the volume of the soft tissue envelope. Although very infrequent, soft tissue coverage with a cutaneous or myocutaneous flap could be necessary. Any surgeon treating PJI of the elbow should be prepared to deal with potentially serious wound complications. The thin soft tissue envelope is often even thinner in many patients because of chronic use of immunosuppressants for inflammatory arthropathies. Even the smallest wound breakdown may expose the effective joint space or the implant itself to the external environment. As a result, the surgeon should have a variety of soft tissue coverage procedures in his or her repertoire or should have a working relationship with a plastic surgeon who does.

8.6 Conclusion and future directions As the population ages, the volume of upper extremity arthroplasty continues to grow. As a result, upper extremity PJI poses an even greater burden to both patients and global health systems. Despite significant advances in our understanding of the pathogenesis, diagnosis, treatment, and outcomes of PJI, many challenges and questions remain. The frequently indolent nature of the offending organisms makes establishing a firm diagnosis challenging, particularly since patients do not present with classic signs of infection. As in hip and knee PJI, synovial biomarkers have shown promise as more sensitive and specific tests than traditional serum markers. Though not widely available at this point, development of point-of-care use of these synovial biomarkers would be a significant step forward in the pre- and intraoperative identification of shoulder and elbow PJI. We must also establish what culture-growths represent true pathogens as opposed to colonizing bacteria or even contaminants. This chapter highlights the lack of precise algorithms for both diagnosis and treatment of shoulder and elbow PJI currently. Essential to such algorithms is the development of a consensus definition for both shoulder and elbow PJI, based on a combination of preoperative and intraoperative findings and intraoperative culture results. The evaluation and management of the painful shoulder or elbow arthroplasty remains highly variable and needs to be standardized in such areas as preoperative surgical site preparation, choice and timing of intraoperative antibiotics during revision surgery, number and type of intraoperative cultures obtained during revision surgery, culture methods and length of time for culture incubation, and choice and length of postoperative antibiotic therapy. A consensus definition of PJI and a standardized approach to evaluation and management will aid in developing and interpreting future research studies and will ultimately lead to more refined diagnostic algorithms and clinical treatment pathways. Currently, there are many acceptable forms of treatment for shoulder and elbow PJI, as outlined

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previously. The surgeon must chose a treatment based on the chronicity and virulence of the infection, soft tissue and bony deficiencies, activity level, comorbidities, and the patient's desires. Further studies will clarify the role of each treatment paradigm in specific scenarios and the economic impact of certain treatment methods on both the patients and the health systems.

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