How to manage treatment failure in prosthetic joint infection.

BACKGROUND: Management for prosthetic joint infections remains a challenging area for both infectious diseases and orthopaedic surgery, particularly in the setting of treatment failure. This is compounded by a lack of level 1 evidence to guide approaches. The optimal management of prosthetic joint infections requires a multi-disciplinary approach combined with shared decision making with the patient. AIMS: This article describes the approach to prosthetic joint infections in the setting of treatment failure. SOURCES: Narrative review based on literature review from PubMed. There was no time limit on the studies included. In addition, the reference list for included studies were reviewed for literature saturation with manual searching of clinical guidelines. Management approaches described incorporate evidence- and eminence-based recommendations from expert guidelines and clinical studies, where applicable. CONTENT: The surgical and antimicrobial approaches for prosthetic joint infections are described for first-line treatment of prosthetic joint infections and approaches in the event of treatment failure. Management approaches are based on an understanding of the role the biofilm plays in the pathogenesis of prosthetic joint infections. The management of these infections aims to fulfil two key goals: to eradicate the biofilm-associated microorganisms and, to maintain a functional joint and quality of life. In treatment failure, these goals are not always feasible, and the role of the multi-disciplinary team and shared-decision making are prominent. IMPLICATIONS: Prosthetic joint surgery is a high-volume surgery, and the demand for this surgery is continually increasing. With this, the number of infections requiring expert care will also increase. Eminence-based management approaches have been established to guide treatment failure until knowledge gaps in optimal management are addressed by well-designed, clinical trials.

Chlorhexidine-alcohol versus iodine-alcohol for surgical site skin preparation in an elective arthroplasty (ACAISA) study: a cluster randomized controlled trial.

OBJECTIVES: Surgical site skin preparation is an effective method to prevent wound complications. The optimal agent has not been established, and guidelines contain conflicting recommendations. METHODS: The aim of alcoholic chlorhexidine or alcoholic iodine skin antisepsis (ACAISA) was to assess the efficacy of surgical site skin preparation with 0.5% chlorhexidine gluconate (w/v) in 70% ethanol (v/v) to 1% iodine (w/v) in 70% ethanol (v/v). This was a cluster randomized, controlled, single-centre, assessor-blinded, superiority trial in patients undergoing elective hip or knee arthroplasty. Each surgeon had a set operating day and the unit of randomization was the day of surgery. The primary outcome was superficial wound complication, defined as a composite endpoint of superficial incisional surgical site infection and/or clinically significant wound ooze in the 30 days following arthroplasty. The secondary outcome was any surgical site infection, including prosthetic joint infection. Outcome ascertainment was undertaken by an independent verification panel. The primary analysis was intention-to-treat, performed at the individual level. Taking into account the clustering effect, analysis of primary and secondary outcomes was undertaken at the level of the surgeon. RESULTS: A total of 780 participants were included; 390 participants were allocated chlorhexidine-alcohol and 390 participants were allocated iodine-alcohol. There was no difference in superficial wound complications: 19 (4.9%) versus 15 (3.8%) respectively (OR 1.28; 95%CI 0.62, 2.63; p 0.50). There was an increased odds of surgical site infection in the chlorhexidine-alcohol group compared to iodine-alcohol: 12 (3.1%) versus four (1.0%) respectively (OR 3.06; 95%CI 1.26, 7.46; p 0.014). The odds of prosthetic joint infection were also increased in the chlorhexidine-alcohol arm compared with iodine-alcohol: seven (1.8%) versus two (0.5%) respectively (OR 3.55; 95%CI 1.20, 10.44; p 0.022). CONCLUSIONS: No difference was observed in the primary outcome of superficial wound complications when chlorhexidine-alcohol and iodine-alcohol were compared. However, on a secondary analysis, iodine-alcohol had greater efficacy than chlorhexidine-alcohol for preventing surgical site infection. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000177651.

Direct hospital cost determinants following hip and knee arthroplasty.

OBJECTIVE: Total joint arthroplasty (TJA) places a significant economic burden on health care resources. This cohort study examines the costs associated with arthroplasty in 827 patients undergoing hip and knee TJA from January 2011 to June 2012 at a single center in Melbourne, Australia. METHODS: Data included total inpatient, outpatient, and readmissions costs in the 30 days following TJA. Factors associated with cost were modeled using negative binomial regression and extrapolated to the Australian population. RESULTS: The base cost (i.e., the cost for a patient with no modifying factors) over the first 30 days following TJA was $13,060 Australian (AU) (interquartile range $12,126-14,067 AU). The median length of stay was 4 days (range 2-33 days) and 35 patients (4%) were readmitted in the first 30 days following index TJA, the majority of whom had a surgical site infection (SSI) (74%). The following factors were independently associated with increased costs: SSI, preoperative warfarin therapy, American Society of Anesthesiologists score of 3 or 4, hip TJA, increasing operation time, increasing postoperative blood transfusion requirements, other nosocomial infections, postoperative venous thromboembolism (VTE), pressure ulcers, postoperative confusion, and acute urinary retention. Based on data from the present study, the cost of TJA in Australia is estimated to exceed $1 billion AU per year. Preventable postoperative complications were major cost drivers: SSI and VTE added a further $97 million AU and $66 million AU, respectively, to arthroplasty costs in the first 30 days following surgery. CONCLUSION: This unique study has identified important factors influencing TJA costs and providing guidance for future research and resource allocation.

Alcoholic Chlorhexidine or Alcoholic Iodine Skin Antisepsis (ACAISA): protocol for cluster randomised controlled trial of surgical skin preparation for the prevention of superficial wound complications in prosthetic hip and knee replacement surgery.

INTRODUCTION: Wound complications following arthroplasty are associated with significant impact on the patient and healthcare system. Skin cleansing prior to surgical incision is a simple and effective method to prevent wound complications however, the question of which agent is superior for surgical skin antisepsis is unresolved. METHODS AND ANALYSIS: This cluster randomised controlled trial aims to compare the incidence of superficial wound complications in patients undergoing elective prosthetic hip or knee replacement surgery receiving surgical skin antisepsis with either: 0.5% chlorhexidine gluconate (CHG) in 70% alcohol or 10% povidone in 70% alcohol. The trial will be conducted at an Australian tertiary, university affiliated hospital over a 3-year period involving 750 participants. Participants will be drawn from the surgical waiting list. Consent for this study will be 'opt-out' consent. On a given day, all eligible participants will have skin preparation either with 0.5% chlorhexidine in 70% alcohol or 10% povidone iodine in 70% alcohol. The primary outcome is superficial wound complications (comprised of superficial incisional surgical site infections (SSI) and/or prolonged wound ooze) in the first 30 days following prosthetic joint replacement surgery. Secondary outcomes will include the incidence of wound complications according to the joint replaced, assessment of the causative agents of SSI and cost-effectiveness analysis. The primary analysis is an intention-to-treat analysis including all participants who undergo randomisation and will be performed at the individual level taking into account the clustering effect. ETHICS AND DISSEMINATION: The study design and protocol was reviewed and approved by the St Vincent's Hospital Human Research Ethics Committee (HREC-A 016/14 10/3/2014). Study findings will be disseminated in the printed media, and learned forums. A written lay summary will be available to study participants on request. TRIAL REGISTRATION NUMBER: The trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614000177651.

Factors influencing the cost of prosthetic joint infection treatment.

BACKGROUND: Prosthetic joint infection (PJI) is associated with significant costs to the healthcare system. Current literature examines the cost of specific treatment modalities without assessing other cost drivers for PJI. AIMS: To examine the overall cost of the treatment of PJI and to identify factors associated with management costs. METHODS: The costs of treatment of prosthetic joint infections were examined in 139 patients across 10 hospitals over a 3-year period (January 2006 to December 2008). Cost calculations included hospitalization costs, surgical costs, hospital-in-the-home costs and antibiotic therapy costs. Negative binomial regression analysis was performed to model factors associated with total cost. FINDINGS: The median cost of treating prosthetic joint infection per patient was Australian $34,800 (interquartile range: 20,305, 56,929). The following factors were associated with increased treatment costs: septic revision arthroplasty (67% increase in treatment cost; P = 0.02), hypotension at presentation (70% increase; P = 0.03), polymicrobial infections (41% increase; P = 0.009), surgical treatment with one-stage exchange (100% increase; P = 0.002) or resection arthroplasty (48% increase; P = 0.001) were independently associated with increased treatment costs. Culture-negative prosthetic joint infections were associated with decreased costs (29% decrease in treatment cost; P = 0.047). Treatment failure was associated with 156% increase in treatment costs. CONCLUSIONS: This study identifies clinically important factors influencing treatment costs that may be of relevance to policy-makers, particularly in the setting of hospital reimbursement and guiding future research into cost-effective preventive strategies.

Cost analysis of debridement and retention for management of prosthetic joint infection.

Prosthetic joint infection remains one of the most devastating complications of arthroplasty. Debridement and retention of the prosthesis is an attractive management option in carefully selected patients. Despite this, there are no data investigating the cost of this management modality for prosthetic joint infections. The aim of this case-control study was to calculate the cost associated with debridement and retention for management of prosthetic joint infection compared with primary joint replacement surgery without prosthetic joint infection. From 1 January 2008 to 30 June 2010, there were 21 prosthetic joint infections matched to 42 control patients. Controls were matched to cases according to the arthroplasty site, age and sex. Cases had a greater number of unplanned readmissions (100% vs. 7.1%; p <0.001), more additional surgery (3.3 vs. 0.07; p <0.001) and longer total bed days (31.6 vs. 7.9 days; p <0.001). In addition they had more inpatient, outpatient and emergency department visits (p <0.001, respectively). For patients with prosthetic joint infection the total cost, including index operation and costs of management of the prosthetic joint infection, was 3.1 times the cost of primary arthoplasty; the mean cost for cases was Australian dollars (AUD) $69,414 (±29,869) compared with $22,085 (±8147) (p <0.001). The demand for arthroplasty continues to grow and with that, the number of prosthetic joint infections will also increase, placing significant burden on the health system. Our study adds significantly to the growing body of evidence highlighting the substantial costs associated with prosthetic joint infection.

Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy.

The management of prosthetic joint infections remains a clinical challenge, particularly infections due to methicillin-resistant staphylococci. Previously, this infection was considered a contraindication to debridement and retention strategies. This retrospective cohort study examined the treatment and outcomes of patients with arthroplasty infection by methicillin-resistant staphylococci managed by debridement and retention in conjunction with rifampin-fusidic acid combination therapy. Over an 11-year period, there were 43 patients with infection by methicillin-resistant staphylococci managed with debridement and retention. This consisted of close-interval repeated arthrotomies with pulsatile lavage. Rifampin was combined with fusidic acid for the majority of patients (88%). Patients were monitored for a median of 33.5 months (interquartile range, 20 to 54 months). Overall, 9 patients experienced treatment failure, with 12- and 24-month estimates of infection-free survival of 86% (95% confidence interval [CI], 71 to 93%) and 77% (95% CI, 60 to 87%), respectively. The following factors were associated with treatment failure: methicillin-resistant Staphylococcus aureus (MRSA) arthroplasty infection, a single surgical debridement or ≥4 debridements, and the receipt of less than 90 days of antibiotic therapy. Patients with infection by methicillin-resistant coagulase-negative staphylococci (MR-CNS) were less likely to fail treatment. The overall treatment success rate reported in this study is comparable to those of other treatment modalities for prosthetic joint infections by methicillin-resistant staphylococci. Therefore, the debridement and retention of the prosthesis and rifampin-based antibiotic therapy are a valid treatment option for carefully selected patients.

Early onset prosthetic hip and knee joint infection: treatment and outcomes in Victoria, Australia.

BACKGROUND: Prosthetic joint infection (PJI) remains a devastating complication of arthroplasty. There are no internationally endorsed consensus management guidelines and treatment approaches differ widely. AIM: The aim of this multicentre study was to examine treatment approaches and predictors of treatment failure in patients with early PJI managed in hospitals in Victoria, Australia. METHODS: This cohort study was conducted across 10 hospitals over a three-year period (January 2006 to December 2008) and involved 147 patients who presented with early PJI. FINDINGS: Most patients (76%) were managed with debridement and retention of the prosthesis. Patients were followed for a median 20 months (interquartile range: 7-36). Overall 43 patients experienced treatment failure with a 12-month infection-free survival estimate of 76% [95% confidence interval (CI): 68-83%]. The following factors were associated with treatment failure: septic revision arthroplasty (hazard ratio: 7.5; 95% CI: 2.4-23.1; P < 0.0001), hypotension at presentation (4.9; 1.5-15.7; P = 0.007), one-stage exchange (3.1; 1.0-9.2; P = 0.048), total duration of antibiotic therapy <90 days: specifically <30 days (18.5; 5.4-63.1; P < 0.001), 30-60 days (8.0; 2.6-23.9; P < 0.001) and 60-90 days (7.3; 2.2-24.4; P = 0.001), respectively. Effective empiric antibiotic therapy was associated with a decreased risk of treatment failure (0.20; 0.09-0.47; P < 0.001). CONCLUSIONS: The management approach in Australia differs from that used elsewhere in the world. We have identified a number of clinically relevant risk factors for treatment failure that may impact on treatment recommendations.

Risk factors for prosthetic hip and knee infections according to arthroplasty site.

Prosthetic joint infection is a devastating complication of arthroplasty. Previous epidemiological studies have assessed factors associated with arthroplasty infections but have not assessed the impact of comorbidity on infection at different arthroplasty locations. We used a case-control design to investigate risk factors for prosthetic joint infection with reference to the anatomical site. During an eight-year period at a single hospital, 63 patients developed a prosthetic joint infection (36 hips, 27 knees). Cases of prosthetic hip or knee joint infection were matched 1:2 to controls. The results suggest that factors associated with arthroplasty infections differ with anatomical location. Following knee arthroplasty, wound discharge was associated with an increased risk of prosthetic joint infection whereas the presence of a drain tube reduced the risk. By contrast, increased body mass index, increased drain tube loss and superficial incisional surgical site infections (SSIs) were associated with prosthetic hip infection. When analysed as a combined cohort, systemic steroid use, increased SSI drain tube losses, wound discharge, and superficial incisional SSIs were predictors of infection.

Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone.

Information is required about treatment outcomes of Gram-negative prosthetic joint infections treated with prosthesis retention and surgical debridement, especially where biofilm-active antibiotics such as fluoroquinolones are used. The outcome of 17 consecutive patients with an early Gram-negative prosthetic joint infection who had been treated with prosthesis retention and surgical debridement was analysed. Enterobacteriaceae were isolated in 16 patients and infections were mixed with other organisms in 13 (76%) patients. The median joint age was 17 days and the median duration of symptoms before debridement was 7 days. All patients initially received intravenous ß-lactam antibiotic therapy and 14 patients were then treated with oral ciprofloxacin. Treatment failure occurred in two patients over a median period of follow-up of 28 months. In only one patient was a relapsed Gram-negative infection responsible for the failure and this patient had not been treated with ciprofloxacin. The 2-year survival rate free of treatment failure was 94% (95% CI, 63-99%). Prosthesis retention with surgical debridement, in combination with antibiotic regimens including ciprofloxacin, was effective and should be considered for patients with early Gram-negative prosthetic joint infection.