 MANAGING PERIPROSTHETIC JOINT INFECTION

Deep infection after hip arthroplasty STAYING CURRENT WITH CHANGE

M. R. Whitehouse, M. C. Parry, S. Konan, C. P. Duncan From The University of British Columbia, Vancouver, Canada

Periprosthetic joint infection (PJI) complicates between 0.5% and 1.2% primary total hip arthroplasties (THAs) and may have devastating consequences. The traditional assessment of patients suffering from PJI has involved the serological study of inflammatory markers and microbiological analysis of samples obtained from the joint space. Treatment has involved debridement and revision arthroplasty performed in either one or two stages. We present an update on the burden of PJI, strategies for its diagnosis and treatment, the challenge of resistant organisms and the need for definitive evidence to guide the treatment of PJI after THA. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):27–30.

 M. R. Whitehouse, FRCS (Tr&Orth), PhD, MSc (Orth Eng), Consultant Senior Lecturer in Trauma and Orthopaedics, Musculoskeletal Research Unit, 1st Floor Learning & Research Building, School of Clinical Sciences University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK  M. C. Parry, FRCS (Tr&Orth), MD, BSc, Locum Consultant in Orthopaedic Oncology, Orthopaedic Oncology Unit Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Birmingham, B31 2AP, UK.  S. Konan, FRCS (Tr&Orth), MD, Lower Limb Reconstruction and Oncology Fellow,  C. P. Duncan, MD, MSc, Professor of Orthopaedics, Department of Orthopaedics The University of British Columbia, 3rd Floor, 910 West 10th Avenue, Vancouver, BC, V5Z 4E3, Canada. Correspondence should be sent to Mr M. R. Whitehouse; e-mail: michael.whitehouse@ bristol.ac.uk ©2016 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.98B1. 36294 $2.00 Bone Joint J 2016;98-B(1 Suppl A):27–30.

New realities of societal cost and burden Reduction in the costs and burden of periprosthetic joint infection (PJI) may be realised via approaches targeted at its prevention, diagnosis and treatment. Decolonisation by empirical or screen-andtreat strategies with mupirocin ointment before total hip arthroplasty (THA) is safe, and cost effective; and can reduce the risk of surgical site infection (SSI).1 Short-term perioperative systemic antibiotics have equal efficacy, lower cost and reduced risk of complications and resistance associated with long-term courses.2 Using vancomycin as prophylaxis for methicillin resistant Staphylococcus aureus (MRSA) proven cases has been found to be cost-effective when the rate of MRSA infection is > 0.25% and the rate of other infections is > 0.2% or more.3 The use of antibiotic impregnated bone cement reduces the incidence of deep but not superficial infection in THA4 but may not be cost effective currently when revision due to infection alone is considered.5 Its use is standard in European practice and there is good evidence to support this.6 Current cost-effective strategies for the diagnosis of PJI include; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as screening tools as discussed below;7 and aspiration of the hip for culture. Colorimetric strip tests for leukocyte esterase in the synovial fluid may become an alternative and has been adopted as a minor criterion in the international consensus on PJI.8

VOL. 98-B, No. 1, JANUARY 2016

Treatment costs of PJI per patient vary dramatically according to the location, period and treatment strategies in studies. A one-stage exchange often requires a longer initial stay in hospital9 for the administration of parenteral antibiotics, whereas the two-stage approach requires an additional admission and operation that costs 1.7 times more.10 The overall costs and rates of failure of treatment are much higher in MRSA infections.11

New strategies in screening and prophylaxis Contemporary strategies focus on optimising modifiable risk factors.12 Rapid screening for nasal Staphylococcus aureus colonisation is possible using real time polymerase chain reaction (PCR) assay and decolonisation reduces the incidence of deep infection.13 Universal decolonisation without screening is an alternative strategy.14 It is well established that peri-operative antimicrobial prophylaxis reduces the risk of SSI by > 80%.2 Cephalosporins have emerged as the agent of choice worldwide; with the option of glycopeptides,2 and vancomycin15 in conjunctive roles for known MRSA colonisation. The role of laminar airflow and body exhaust suits has been questioned.16,17 Antibiotic prophylaxis is not necessary for dental procedures as the risk of PJI is not increased18 and prophylaxis does not decrease the risk of subsequent PJI.18 Coating of implants with materials such as silver reduces bacterial adherence but robust clinical evidence to support their use is awaited.19 27

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New directions in achieving diagnostic accuracy The sensitivity and specificity of established serum inflammatory markers such as CRP and ESR are approximately 88% and 74% and 75% and 70%, respectively.20 interleukin (IL)-6 (sensitivity 97%, specificity 91%);20 procalcitonin (sensitivity 33%, 98% specificity);21 and alpha defensin-1 (sensitivity 100%, specificity 95%) have demonstrated higher accuracy.22 IL-6 has a lower mean half-life (15 vs 62 hours for CRP), making it useful in the early postoperative phase and in differentiating the aetiology of elevated serum markers in late PJI. Advanced imaging modalities have emerged but have high costs and limited availability.18 F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has a sensitivity and specificity of 82.1% and 86.6%, respectively.23 The white cell count in synovial fluid is influenced by inflammatory arthritis and metal debris.24,25 Testing adjunctive markers such as leucocyte esterase enzyme has shown 100% specificity.26 Some other markers (α-defensin 1-3, neutrophil elastase 2, bactericidal/permeabilityincreasing protein, neutrophil gelatinase-associated lipocalin, and lactoferrin) have also shown 100% sensitivity and specificity.27 There is increasing emphasis on the role of specific media (cooked meat broth, thioglycolate broth and blood culture bottles) for tissue culture28,29 as well as the need for an extended period of culture (seven to 14 days) particularly pertinent to propinobacterium acnes.30 Bacteria and biofilms can be dislodged from the surfaces of explanted implants by sonication. This increases the sensitivity (79%) compared with tissue culture (61%) while preserving specificity (99%) which is maintained in the presence of recent antibiotic treatment.31 The turnaround time of tissue culture, and false positive and false negative results can be reduced by the use of 16S rRNA gene PCR combined with sequencing (16SPCR). The latter has higher specificity (100% vs 94%) for the diagnosis of PJI,28 however, it does not provide antimicrobial susceptibility. Treatment modalities Treatment modalities include radical debridement with retention of the prosthesis, one-stage (or immediate) exchange, two-stage (or delayed) exchange and excision arthroplasty. Long-term antibiotic suppression may be used where further surgery is contraindicated. Rarely, amputation may be required to achieve control of life-threatening infection. A multidisciplinary approach to treatment by surgeons experienced in the treatment of PJI in conjunction with a microbiologist or infectious diseases physician is recommended. In the acute phase following the development of PJI, radical debridement with retention of the prosthesis may be attempted. The procedure must be performed before a biofilm has formed.32 Thresholds of < three weeks for acute haematogenous PJI and < 30 days following the initial procedure are recommended.33 The implants must remain well-fixed with no sinus tract formation.33

One-stage revision is more commonly performed in Europe but two-stage procedures predominate.34 Reinfection rates of 8.6% (95% CI 4.5 to 13.9) and 10.2% (95% CI 7.7 to 12.9) have been reported in a systematic review for one- compared with two-stage procedures in unselected patients.9 The recommended criteria for selecting patients for a one-stage procedure include a good soft-tissue envelope, a known pathogen sensitive to an antimicrobial agent with good bioavailability, where antibiotic impregnated bone cement can be used and bone grafting is not required.33 Good rates of control of infection have been reported in small series where allograft was used35 and cementless onestage exchange may result in reasonable rates of control36 suggesting these are not absolute contraindications. In a two-stage procedure, no spacer, antibiotic cement beads, a static spacer or an articulating spacer may be used. Beads and static spacers have equivalent rates of control of infection, but static spacers show improved interim mobility for the patient, decreased operating time at the secondstage and lower transfusion requirements.37 Articulating spacers are associated with similar rates of control38 and good function,38 but may be associated with rates of complications related to the spacer of > 10%39 and require synovectomy at the second-stage.40 Excision arthroplasty is recommended in non-ambulatory patients, those with poor bone stock or soft tissues, resistant bacteria, failed previous two-stage or repeated onestage revisions.33 While amputation is an option for clearance, it is only recommended following discussion with a tertiary centre specialising in dealing with PJI.

Must everything be removed every time? In an attempt to reduce the morbidity and bone loss of delayed exchange, partial exchange has been proposed.41 The technique requires aggressive debridement, mechanical cleansing of retained components and soft-tissue and a custom made antibiotic-laden cement articulating femoral head between stages. Failures are more likely with previous failed two-stage revision and resistant organisms.41 There is supporting evidence of the strategy in total knee arthroplasty42 but the procedure remains controversial as it does not allow biofilm formation to be adequately addressed, increasing the risk of recurrent infection. If an interface is osseointegrated and well sealed, it may be inaccessible to bacteria and hence not require removal at revision surgery as long as the ‘effective joint space’ is adequately addressed. The Exeter group have reported control of infection equivalent to other two-stage revision series using this strategy.43,44 The technique requires thorough radiological and intra-operative assessment of the integrity of the interface, the removal of all membrane and debris and preparation to permit antibiotic elution from cement mantles. Due to the demands of delivering such strategies, they are likely to remain best employed in selected patients in high-volume centres. CCJR SUPPLEMENT TO THE BONE & JOINT JOURNAL

DEEP INFECTION AFTER HIP ARTHROPLASTY

The challenge of MRSA/SE The incidence of SSIs due to resistant organisms, including MRSA and methicillin resistant Staphylococcus epidermidis (MRSE) has increased significantly in recent years, accounting for up to 50% of PJIs in some studies.45 There is an epidemic of community associated MRSA within many North American populations.46 The change in virulence, coupled with the emergence of strains resistant to daptomycin, vancomycin and linezolid47 suggests that these strains will become more prevalent and difficult to treat. Debridement and exchange of modular components when there are resistant organisms has had variable success.48 It is associated with high rates of failure in resistant staphylococci49 and evidence from PJI of the knee suggests poor outcomes.50 The one-stage approach to the treatment of PJI of the hip is popular in Europe.51 Variable outcomes ranging from complete success to complete failure, often in studies including small numbers of resistant cases within a larger cohort, have been reported.36,52-54 A comprehensive review has identified such pathogens with a high rate of failure.55 Eradication of infection with a two-stage approach can be achieved in up to 98% of patients38 however, with resistant staphylococci, the success rates are lower, in some studies only 48%.56-59 Immediate (one-stage) or delayed (two-stage) exchange Proponents of the one-stage approach point to the improved morbidity, functional and financial outcomes offered by this approach.32,51 In contrast, and largely due to the perceived higher rates of re-infection, the two-stage or delayed exchange remains the gold standard in North America.60 How best to manage PJI of the hip remains contentious. The heterogeneous nature of the patients affected together with the multifactorial aetiology and pathogenesis, makes direct comparison between each approach difficult. In the absence of randomised trials on matched populations, systematic reviews, meta-analyses and statistical modelling have been used to try to identify which approach offers lower re-infection rates. Lange et al61 estimated three more infections per 100 patients with an immediate exchange but highlighted the imprecise statistical estimate based on the poor quality of the available data. Using a Markov cohort simulation decision analysis, Wolf et al62 favoured immediate exchange at both 12 months and ten years post-operatively with similar limitations. Klouche et al63 performed a non-randomised prospective study on two cohorts of patients stratified to receive either immediate (one-stage) or delayed (two-stage) exchange on the basis of factors related to the patient and the organism. They found lower re-infection rates and higher initial cure with immediate exchange. Beswick et al9 performed a systematic review of longitudinal studies, excluding studies on selected patients, those lacking an intention to treat, those including both hip and knee PJI, and studies with follow-up of < two years. No differences in the eradication of infection were found in the VOL. 98-B, No. 1, JANUARY 2016

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62 studies and > 4000 patients included. Leonard et al64 identified nine studies comparing immediate and delayed exchange and demonstrated a role for immediate exchange in selected patients with improvements in functional outcomes.

The new way forward – prospective randomised controlled trial (pRCT) The evidence available to guide the decision between treatment modalities in revision for PJI of the hip is reliant on the consideration of longitudinal studies with known selection biases and poor comparator groups. Thorough systematic review of the literature where unselected patients are considered, demonstrates no difference in re-infection rates between patients treated with one- or two-stage exchange.9 Equipoise thus exists regarding the optimum treatment of patients suffering from PJI in THA, and this justifies the conduct of a pRCT. PJI following primary THA is relatively rare and re-infection rates following revision for PJI are approximately 10% at two years post-operatively.9 Although re-infection appears to be a relatively well-defined end point, the difference in treatment strategies with post-operative antibiotics and variations in the long-term follow-up of patients in different units leads to problems with generating comparable outcomes. Reinfection as an endpoint is hampered by similar problems as survivorship as an endpoint65 and as such, a properly constructed prospective multicentre trial into the treatment of PJI should focus on patient-based outcome measures and include microbiological and surgeon-based outcomes. Author contributions: M. R. Whitehouse: Authored abstract and sections 4, 5 and 8, co-ordinated contributions, produced, edited and approved final manuscript. M. C. Parry: Authored sections 6 and 7, edited and approved final manuscript. S. Konan: Authored sections 1, 2 and 3, edited and approved final manuscript. C. P. Duncan: Presentation at CCJR, conceptualisation and design of manuscript plan, edited and approved final manuscript. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by J. Scott. This paper is based on a study which was presented at the 31st Annual Winter 2014 Current Concepts in Joint Replacement® meeting held in Orlando, Florida, 10th-13th December.

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37. Hsieh P- H, Shih C- H, Chang Y- H, et al. Two-stage revision hip arthroplasty for infection: comparison between the interim use of antibiotic-loaded cement beads and a spacer prosthesis. J Bone Joint Surg [Am] 2004;86-A:1989–1997. 38. Biring GS, Kostamo T, Garbuz DS, Masri BA, Duncan CP. Two-stage revision arthroplasty of the hip for infection using an interim articulated Prostalac hip spacer: a 10- to 15-year follow-up study. J Bone Joint Surg [Br] 2009;91-B:1431–1437. 39. Neumann DRP, Hofstaedter T, List C, Dorn U. Two-stage cementless revision of late total hip arthroplasty infection using a premanufactured spacer. J Arthroplasty 2012;27:1397–1401. 40. Fink B, Rechtenbach A, Büchner H, Vogt S, Hahn M. Articulating spacers used in two-stage revision of infected hip and knee prostheses abrade with time. Clin Orthop Relat Res 2011;469:1095–1102. 41. 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Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clin Orthop Relat Res 2007;461:48–53. 57. Leung F, Richards CJ, Garbuz DS, Masri BA, Duncan CP. Two-stage total hip arthroplasty: how often does it control methicillin-resistant infection? Clin Orthop Relat Res 2011;469:1009–1015. 58. Murray TG, Cochran J, Krebs VE, Barsoum WK. Do resistant organisms affect success of two-stage reimplantation for prosthetic hip infections? Curr Orthop Pract 2011;22:180–184. 59. Mittal Y, Fehring TK, Hanssen A, et al. Two-stage reimplantation for periprosthetic knee infection involving resistant organisms. J Bone Joint Surg [Am] 2007;89-A:1227–1231. 60. Matthews PC, Berendt AR, McNally MA, Byren I. Diagnosis and management of prosthetic joint infection. BMJ 2009;338:1773. 61. Lange J, Troelsen A, Thomsen RW, Søballe K. Chronic infections in hip arthroplasties: comparing risk of reinfection following one-stage and two-stage revision: a systematic review and meta-analysis. Clin Epidemiol 2012;4:57–73. 62. Wolf CF, Gu NY, Doctor JN, Manner PA, Leopold SS. Comparison of one and two-stage revision of total hip arthroplasty complicated by infection: a Markov expected-utility decision analysis. J Bone Joint Surg [Am] 2011;93-A:631–639. 63. Klouche S, Leonard P, Zeller V, et al. Infected total hip arthroplasty revision: oneor two-stage procedure? Orthop Traumatol Surg Res 2012;98:144–150. 64. Leonard HAC, Liddle AD, Burke O, Murray DW, Pandit H. Single- or two-stage revision for infected total hip arthroplasty? A systematic review of the literature. Clin Orthop Relat Res 2014;472:1036–1042. 65. Wylde V, Blom AW. The failure of survivorship. J Bone Joint Surg [Br] 2011;93B:569–570. CCJR SUPPLEMENT TO THE BONE & JOINT JOURNAL

Deep infection after hip arthroplasty: staying current with change.

Periprosthetic joint infection (PJI) complicates between 0.5% and 1.2% primary total hip arthroplasties (THAs) and may have devastating consequences. ...
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