Shoulder:Sepsis of the Shoulder

Bullet Points

• Periprosthetic shoulder infection is rare but potentially devastating. The rate of periprosthetic shoulder infection is increased in cases of revision procedures, reverse shoulder implants and comorbidities. One specific type of periprosthetic shoulder infection is the occurrence of low-grade infections caused by non-suppurative bacteria such as Cutibaterium acnes or Staphylococcus epidemermidis.
• Success of treatment depends on micro-organism identification, appropriate surgical procedures and antibiotic administration efficiency. Post-operative early periprosthetic shoulder infection can be treated with simple debridement, while chronic periprosthetic shoulder infection requires a one- or two-stage revision procedure. Indication for one-time exchange is based on pre-operative identification of a causative agent. Resection arthroplasty remains an option for low-demand patients or recalcitrant infection.

Key Words

Infection; Arthroplasty; Shoulder; Cutibacterium acnes; Propionibacterium; Revision.

== Introduction == While more than 66 000 prosthetic shoulder procedures were performed in 2011 in the United States, the rate of post-operative infection seems to remain stable with 0.98% of cases.1-3 However, when infection occurs, this complication is always devastating with significant clinical and socioeconomic consequences.2 The rate is higher after revision surgery than after a primary procedure and reaches close to 5% in cases of reverse shoulder arthroplasty.4,5 Patients undergoing primary RSA are found to have a six times greater risk of infection compared with patients having primary unconstrained total shoulder arthroplasty.6 Arthroplasties for trauma are more at risk of infection than those from other causes.6 Comorbidities such as coagulopathy, renal failure, diabetes, lupus erythematosus, rheumatoid arthritis, intra-articular steroid injections and corticosteroid therapy increase the risk of periprosthetic shoulder infection.7 PSI is the major cause for revision within the first two post-operative years after an arthroplasty.8

The aim of this review is to investigate PSI from diagnosis to prevention and to report the main results of different therapeutic options.

Microbiology

Prevention

Antibiotic prophylaxis is not specific to shoulder arthroplasty compared with other arthroplasties. Intravenous cephalosporine (2 g) administration is mandatory, given 30 minutes before the skin incision in many countries. However, some authors recommend a single 160 mg of gentamicin by intra-articular injection at the end of the procedure to reduce the risk of PSI.15 Saltzman et al1.6 have shown that pre-operative preparation of the surgical site with chlorhexidine gluconate and 70% isopropyl alcohol was more effective than iodine povacrylex and 74% isopropyl alcohol and povidone-iodine at eliminating overall bacteria, and that the two first ones were more effective than povidone-iodine regarding coagulase-negative Staphylococcus.

Hair removal is commonly performed before orthopaedic procedures and the use of razors is classically discouraged because micro-abrasions are created by shaving. However, removal of axillary hairs for shoulder surgery did not prove to have any effect on the cell-count of Cutibacterium acnes before surgical preparation.17

Cutibacterium (Propionibacterium) acnes

Cutibacterium acnes (formerly Propionibacterium acnes) is a non-spore-forming, anaerobic, gram-positive bacillus. It is of low virulence and therefore can be a commensal in the lipid-rich sebaceous follicles and deep layers of the skin, conjunctiva, external auditory canal, respiratory tract and intestinal tract. Cutibacterium acnes mostly colonises the pilosebaceous follicles in the skin of the upper-body, especially the head, neck, shoulders and axilla. Pathogenic activity of the organism has, however, been shown in conditions such as meningitis, septic arthritis, osteomyelitis, chronic prostatitis and sarcoidosis. Cutibacterium acnes expresses proteins required for cell-adherence, which are also antigenic and therefore capable of initiating an inflammatory response of the host’s innate immune system within the joint. Cutibacterium acnes also secretes cytotoxic chemicals and enzymes designed to degrade body tissues, which can be harmful within the shoulder capsule. Furthermore, Cutibacterium acnes is also able to secrete and live within an extracellular polysaccharide biofilm aiding joint colonisation and micro-colony formation, as well as avoid phagocytosis and survive macrophage engulfment. The combination of the bacterium’s upper-limb distribution and role in prosthetic joint infection is now forcing shoulder surgeons to consider Cutibacterium acnes as an ‘orthopaedic pathogen’.

Drug resistance

Patient knowledge about Cutibacterium acnes is mostly limited to acne vulgaris, the skin infection present in the vast majority of young adults and teenagers. Hormonal changes and genetics cause sebaceous gland inflammation, dysfunction and proliferation providing an environment for the opportunistic P. acnes. The treatment of this skin condition with experimental courses of broad-spectrum antibiotics, often combined with poor compliance, is thought to be a contributor to antibiotic resistance. Gold standard antibiotics such as penicillins, vancomycin, tetracyclines and erythromycin often eradicate the bacterium, however, over half of P. acnes cultures now carry resistance to more than one of the above antibiotics.

Incidence and Prevalence

Over the past decade, Cutibacterium acnes has become increasingly recognised as a cause of infection in orthopaedic surgery, especially when prosthesis is involved. With regards to shoulder replacement surgery, one study reported infection rates for primary shoulder replacement to be less than 4% but, following reverse replacement, to be as high as 18%. In this study the most common bacteria identified were Staphylococcus epidermis and Cutibacterium acnes. However, in a retrospective review over 7 years carried out in Canada, 80 patients were identified who underwent joint cultures after primary shoulder arthoplasty and Cutibacterium acnes was found to be the only significant infectious agent in 25% of participants, making it the most common pathogenic organism. A study of periprosthetic joint infections after total shoulder arthroplasty (in the last 33 years) found that Staphylococcus was the dominant organism in the vast majority of cases, whereas, from 2001 – 2008, the incidence of Cutibacterium acnes was found to be almost as high as Staphylococcus. This increasing incidence could be the result of changes in the microbiology of shoulder infections, heightened awareness of the organism, better surveillance or improved laboratory diagnostic techniques Cutibacterium acnes appears to be a prominent aggressor and is becoming more prevalent.


Risk Factors

Recorded risk factors for Cutibacterium acnes infection are male gender, surgery of the upper body (especially the shoulder), increased duration of surgery and, interestingly, being the first surgery of the day. (3, The predominance of Cutibacterium acnes in shoulder infections has been linked with the presence of the axillary lymph nodes. A study that involved culturing the epidermis of wounds during revision surgery, found that 16 of the 18 males involved had Cutibacterium acnes infection whereas only 7 of the 12 female subjects tested positive. Further studies have also found that male gender and prior prosthetic implants are significant risk factors for Cutibacterium acnes infection. The male predisposition has been linked with the habitat of Cutibacterium acnes being in the hair follicles and therefore the upper body of males would harbour more of the bacterium. Furthermore, males were found to have over 2.5 times higher risk than females after shoulder arthroplasty. Interestingly, if shoulder arthroplasty was performed following trauma rather than elective surgery, the risk of infection was nearly 3 times higher. Reverse shoulder arthroplasty again was shown to increase the risk of infection with Cutibacterium acnes. Younger age was also identified as a risk factor, with each year of increasing age causing a risk reduction of 5%. Body Mass Index and diabetes mellitus, which are usually associated with increased risk of infection, were not found to be risk factors. 

From the literature it is evident that patients most at risk of Cutibacterium acnes infection are young people, males, those who have undergone upper limb surgeries (especially reverse shoulder replacements) and those who have surgery following trauma.


Diagnosis

Despite laboratory and investigative advances, the diagnosis of shoulder infections due to relatively low-virulence organisms, like Cutibacterium acnes, remains difficult. The non-specific clinical presentation, inadequate culture performance and the inability to accurately interpret positive cultures mean that diagnosis can be delayed. Research has found that inflammatory markers usually indicative of infection may not be raised in Cutibacterium acnes infection. In 2014, in a clinic in the US, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were both raised in only 10% of patients who were identified as having Cutibacterium acnes infections of the shoulder. In a further study, the sensitivities of CRP and ESR in the shoulder were found to be 42% and 16% respectively, whereas in the lower limbs the sensitivities for CRP and ESR were 88% and 75% respectively. Thus, although the sensitivity and specificity of these inflammatory markers are strong in the lower limbs, they are poor indicators of post-operative shoulder infections. These data fit well with the distribution of Cutibacterium acnes and its indolent nature. It has been further suggested that, due to its slow growth, Cutibacterium acnes needs longer culture times (up to two weeks), making it harder to spot. Furthermore, lowering the threshold for diagnosis (concentration of neutrophils in the tissues) would increase sensitivity because of the low inflammatory behavior of Cutibacterium acnes.

Clinical Presentation

A common assumption is that the origin of Cutibacterium acnes infection is in the dermis of the patient’s skin and that it travels from the surface to contaminate the surgical site. Surface sterilisation before surgery does not, however, eradicate the bacterium as the organism actually resides deep in the sebaceous glands. Scalpel incisions slice through these follicles, allowing for seeding and leakage of the bacteria. Innovative methods of sterilization may therefore be required to penetrate the dermis and reduce Cutibacterium acnes spread. Further, the need for intraoperative screening of wounds and prolonged cultures to assess the risk of developing a postoperative shoulder infection has been emphasised. For low-grade Cutibacterium acnes shoulder infections, pain may be the only symptom, followed by stiffness with all other signs of infection being absent. Periprosthetic joint infections can be extremely serious and may result in loss of normal function of the joint or even progress to sepsis.

A study which focussed on postoperative pain, found that patients felt pain for an average of 3 months before diagnosis of Cutibacterium acnes infection and that the mean time from surgery to diagnosis was almost 2 years. It was also suggested that the variance in the clinical presentation of shoulder infections may not only be due to the non-specific clinical manifestation of Cutibacterium acnes, but also due to co-infection with other bacteria within the surgical site.

Treatment

Debridement

Debridement, irrigation and multiple deep samples may be proposed in cases of acute infection in order to save the prosthesis. Coste et al27 treated eight cases of acute infection with debridement and succeeded when it was performed within eight days after the diagnosis. They concluded that the earlier the debridement is done, the more effective it is in eradicating the infection. This procedure can be repeated, based on the patient’s response.28 Moreover, mobile parts of the prosthesis may be exchanged during the procedure especially in case of RSA (glenosphere, polyethylene liner) providing better access for debridement. Then, an appropriate antibiotics regime is required for a minimum of four weeks.21,28,29 However, the rate of success reported in the literature is only in the range of 50% to 95%.22,27-29

Cement spacer

An antibiotic-loaded cement spacer can be used either permanently or as the first step of a two-stage revision procedure. In this case, it maintains the space and soft-tissue tension for re-implantation and theoretically releases antibiotics to decrease the growth of microorganisms. Antibiotic mean concentration peak is reached at day 1 and dramatically decreases during the following seven days.30 Levy et al31 described a ‘functional cement spacer’ model, which is made of a hemi-arthroplasty coated with cement. In their series of 14 patients initially chosen for a two-stage procedure, nine did not undergo a prosthesis re-implantation because of satisfactory clinical outcomes. On the other hand, Verhelst et al32 did not prove any difference between patients with a cement spacer and resection arthroplasty regarding infection control and clinical outcomes. Complications of the cement-spacer such as breakage, glenoid erosion or dislocation have been reported.32

One-stage revision arthroplasty

Based on the experience of knee and hip infection management, a single-stage exchange is proposed as a reasonable option when the infecting micro-organism is satisfactorily identified. The advantages are a reduced hospital stay, costs, period of antibiotic administration and the best clinical outcomes (Table 2).9,22,27,29,33-37 Klatte et al33 reported the outcomes of the largest single-centre series of 35 patients with a mean follow-up of 4.7 years. The authors excised infected tissues, thoroughly irrigated the wound using pulsatile lavage with polyhexanide before re-implantation and delivered specific intravenous antibiotherapy for an average of two weeks post-operatively. The success rate was more than 90%. No recurrence was observed in the series of Coste et al.,27 Ince et al34 and Cuff et al.35 The presence of a productive fistula seems not to be a contra-indication for many authors.33,36 Beekman et al36 performed a one-stage revision in 11 cases of RSAs, among which eight had a fistula, and achieved a success rate of 90%.

Two-stage revision arthroplasty

In a medically stable patient with a high demand, a two stage revision procedure is generally accepted (Table).22,27,29,33,38-40 It is highly recommended when the microorganism responsible for the infection is unknown. The first step consists of infection eradication after prosthetic removal: an antibiotic-loaded cement spacer is often implanted and general antibiotics are administrated, secondarily adapted to the micro-organism(s) identified. Antibiotics are generally continued for six to eight weeks. Markers such as CRP or IL-6 have been shown to be valuable to predict the eradication of infection and, so, the time of re-implantation.41,42 However, IL-6 seems to be normalised faster than CRP and allows earlier revision for better outcomes.41 An iterative irrigation and debridement could be proposed in case of persistent infection. For re-implantation, RSA has been gaining ground in recent years as the implant of choice. First, it allows a larger debridement at the first stage with less concern for soft-tissue preservation. Secondly, it offers the possibility of addressing the glenoid bone defect with or without bone graft. Shirwaiker et al43 reported that there is still uncertainty whether two-stage revision is superior to one-stage (

Resection arthroplasty

Shoulder resection should remain a salvage procedure for frail or low-demand patients, and recalcitrant infection. It offers the option of a single definitive procedure for infection eradication. It has been shown that functional results are poor, but pain relief is achieved in more than 50% of cases.9,44 Rispoli et al44 reported a mean active elevation of 70° at long-term follow-up after ‘anatomical’ shoulder arthroplasty removal. Verhelst et al32 demonstrated that preservation of the tuberosities is a predictive factor for better results, because it can avoid antero-superior subluxation of the humerus. In cases of RSA, Jacquot et al21 did not improve functional outcomes after removal of the implant and identified a high rate of post-operative complications. Bone loss and soft-tissue impairment after such constrained prostheses could partly explain these findings. Despite Jacquot21 and Coste’s27 studies, the literature reports a high rate of infection eradication, reaching more than 90% of cases.9,27,29,32,44,45

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