Protective effect of N-acetylcysteine in prosthetic joint infection: A nationwide population-based cohort study

PurposeThis nationwide population-based retrospective cohort study evaluated the protective effect of N-acetylcysteine against prosthetic joint infection after hip or knee joint replacement.MethodsPatients receiving N-acetylcysteine after hip or knee joint replacement between 2000 and 2015 were identified from the Taiwan National Health Insurance Research Database. Each patient receiving N-acetylcysteine was matched to four controls based on age, sex, and index year. All subjects were followed-up from the index date to December 31, 2015. The Cox proportional hazards regression model was used to assess the risk of prosthetic joint infection.ResultsA total of 1478 patients were included in the study group, and 5912 matched subjects not receiving N-acetylcysteine were included in the control group. After adjusting for age, sex, insured premium, comorbidities, and immunosuppressive agent use, no significant difference in the risk of prosthetic joint infection was found between the two groups. A higher N-acetylcysteine dose (>360 cumulative defined daily dose) significantly decreased the risk of prosthetic joint infection (adjusted hazard ratio = 0.891; 95% confidence interval = 0.599–0.989; p = 0.042). The protective effect of N-acetylcysteine was observed only in the group of prosthetic joint infection within 5 years (adjusted hazard ratio = 0.801; 95% confidence interval = 0.581–0.980; p = 0.040).ConclusionsHigh cumulative dose of N-acetylcysteine (>360 cumulative defined daily dose) can effectively reduce the risk of prosthetic joint infection in patients undergoing knee or hip joint replacement surgery within 5 years.     

How to manage treatment failure in prosthetic joint infection

BackgroundManagement 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.AimsThis article describes the approach to prosthetic joint infections in the setting of treatment failure.SourcesNarrative 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.ContentThe 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.ImplicationsProsthetic 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.     

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29–104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.     

Continuous high-dose vancomycin combination therapy for methicillin-resistant staphylococcal prosthetic hip infection: a prospective cohort study

Few data are available on treatment and outcome of methicillin-resistant (MR) staphylococcal prosthetic joint infections. Vancomycin remains the treatment of choice for these infections, but its efficacy and safety in bone-and-joint infections are insufficiently documented. We conducted a prospective cohort study on 60 patients treated between November 2002 and December 2008 for chronic MR staphylococcal (44 S. epidermidis, nine other coagulase-negative Staphylococcus and seven S. aureus) prosthetic hip infections (PHIs). Twentytwo patients had previously undergone surgery for their PHI and 21 had previously received antibiotics. All patients had surgery (exchange arthroplasty for 58 patients, resection arthroplasty for two) and received an antibiotic regimen combining high-dose continuous intravenous vancomycin infusion (target serum concentration 30–40 mg/L) with another antibiotic for 6 weeks, followed by an additional 6 weeks of oral intake. Two years after surgery, infection was considered cured in 41 (68%) patients and only two relapses occurred after one-stage exchange arthroplasty. Nineteen (32%) patients experienced nephrotoxicity that was generally mild (RIFLE class R for 14 patients, class I for four patients and class F for one patient) and most often reversible. Continuous high-dose intravenous vancomycin combination therapy is an effective, feasible and reasonably safe treatment of chronic MR staphylococcal PHI.     

Diagnosis of knee prosthetic joint infection; aspiration and biopsy

BackgroundProsthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. The diagnosis can be challenging and is based on a combination of clinical suspicion, radiographic findings and also biochemical/ microbiological investigations. Our Aim was to review the role of aspiration and biopsy in the diagnosis of PJI in Total Knee Arthroplasty (TKA).Method/resultsAspirated synovial fluid should be analysed by direct culture, via blood culture bottles, EDTA bottles for cell count and ‘point of care’ testing such as leucocyte esterase or alpha defensin. Synovial WCC and PMN cell percentage are important steps in diagnosis of both acute and chronic PJI. A minimum of 5 deep samples using a 5 clean instrument technique should be obtained and sent for tissue culture done either blind or arthroscopic. Formal fluoroscopic guided interface biopsy has also been described with excellent results. In a recent series of 86 TKRs preoperative arthroscopic biopsy group had a sensitivity of 100%, specificity of 94.7%, positive predictive value of 87.4% and a negative predictive value of 100%.ConclusionIn the presence of clinical suspicion with raised biomarkers, it is recommended that aspiration +/- biopsy with synovial fluid testing is performed. Direct culture and cell count are recommended. ‘Point of care tests’ such as Leucocyte Esterase testing should be considered. Duration of culture, including pathogen and host factors, should be discussed with a local microbiology/ID department in the context of a formal multi-disciplinary team.     

Early prosthetic joint infection due to Ureaplasma urealyticum: Benefit of 16S rRNA gene sequence analysis for diagnosis

Detection of the most frequently bacteria involved in prosthetic joint infection (PJI) is usually performed by conventional cultures. We report a case of early PJI due to Ureaplasma urealyticum, diagnosed by 16S rRNA gene sequence analysis, which highlights the interest of molecular methods if fastidious bacteria are involved in PJI.     

Preoperative and perioperative risk factors,and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study

ObjectivesWe aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions.MethodsWe performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort.ResultsIn total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m² (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort.DiscussionPredictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.     

Development and validation of baseline,perioperative and at-discharge predictive models for postsurgical prosthetic joint infection

Objectives

To develop and validate baseline, perioperative and at-discharge risk-scoring systems for postsurgical prosthetic joint infection (PJI) in patients undergoing arthroplasty.

Micromonas (Peptostreptococcus) micros: unusual case of prosthetic joint infection associated with dental procedures

Micromonas (Peptostreptococcus) micros is frequently associated with periodontal disease as well as respiratory, gastrointestinal and female genitourinary tract infections, but only rarely has been reported as a pathogenic agent of prosthetic joint infections. Here we describe a case of a 63-year-old woman with prosthetic joint infection of total hip arthroplasty caused by the anaerobic species Micromonas micros, associated with tooth extraction. Samples obtained intraoperatively and from the oral cavity were positive for the presence of M. micros by culture and by real-time PCR. This case report indicates that infections of prosthetic joints can be associated with dental procedures and that sensitive molecular techniques are necessary for their routine diagnostic.     

The utility of dithiothreitol treatment of periprosthetic tissues and explanted implants in the diagnosis of prosthetic joint infection

PurposeThe methods used for the processing of periprosthetic tissues and explanted implants to improve culture outcome especially in biofilm mediated prosthetic joint infections (PJIs) are still debated upon. Studies have reported that Dithiothreitol (DTT) pretreatment of infected devices gives similar results as sonication. However, none of them evaluated the DTT treatment of periprosthetic tissues and explanted implants in the same cohort. We evaluated the diagnostic utility of DTT treatment of periprosthetic tissue and explanted implants, as compared to the normal saline treatment of periprosthetic tissues and sonication of explanted implants for the diagnosis of PJI.MethodsSeventy-three revision arthroplasty cases were prospectively included in this study. Three to five tissue specimens and the explanted implants were collected from each patient. Periprosthetic tissue samples were processed by both normal saline and DTT treatments. Explanted implants were subjected to both DTT treatment and sonication. Musculoskeletal Infection Society (MSIS) PJI criteria was used as the reference standard for the diagnosis of PJI.ResultsOf the 73 cases enrolled, 34 had PJI and 39 were aseptic failures. The sensitivity of DTT treated periprosthetic tissue culture (PTC) and saline treated PTC was similar (66.6% vs 58.8%, P = 0.25). The specificity of both was 100%. Sonication and DTT treatment of explanted implants showed comparable sensitivity (85.3% vs 82.4%) and specificity (100% vs 97.4%), P > 0.99. Compared to DTT treated PTC, culture of DTT treated explanted implants significantly improved the diagnosis of PJI (P = 0.03).ConclusionsWe could verify that DTT can be used to improve culture outcome in laboratories where biofilm detaching sonication techniques are not available for infected implants. In addition, we showed that it is possible to use DTT for treating tissue biopsies, but larger studies are required to confirm our findings.     

Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective observational cohort study

Prosthetic vascular graft infection (PVGI) is a devastating complication, with a mortality rate of up to 75%, which is especially caused by aortic graft infection. The purpose of this study was to evaluate factors associated with in-hospital mortality of patients with definite graft infection, and with long-term outcome. We reviewed medical records of 85 patients treated for PVGIs defined by positive bacterial culture of intraoperative specimens or blood samples, and/or clinical, biological and radiological signs of infection. In-hospital patient mortality was defined as any death occurring during the initial treatment of the graft infection. Cure was defined as the absence of evidence of relapsing infection during long-term follow-up (≥1 year). Eighty-five patients (54 aortic and 31 limb graft infections) treated by surgical debridement and removal of the infected prosthesis (n=41), surgical debridement without removal of prosthesis (n=34) or antimicrobial treatment without surgery (n=10) were studied. The only microbiological difference observed between patients with early (occurring within 4 months after surgery) vs. late PVGI and between those with aortic vs. limb PVGI was the incidence of PVGI caused by Staphylococcus aureus, which was greater in patients with limb PVGI. Overall cure was observed in 93.2% of 59 patients with a follow-up of a minimum of 1 year. Overall in-hospital mortality was 16.5% (n=14). Two variables were independently associated with mortality: age >70 years (OR 9.1, 95% CI 1.83-45.43, p 0.007) and aortic graft infection (OR 5.6, 95% CI 1.1-28.7, p 0.037).     

The effect of preoperative oral antibiotic use on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow-up

ObjectivesAntibiotics are used for various reasons before elective joint replacement surgery. The aim of this study was to investigate patients' use of oral antibiotics before joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI).MethodsPatients having a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified (n = 23 171). Information on oral antibiotic courses purchased 90 days preoperatively and patients' chronic diseases was gathered. Patients with a PJI in a 1-year follow-up period were identified. The association between antibiotic use and PJI was examined using a multivariable logistic regression model and propensity score matching.ResultsOne hundred and fifty-eight (0.68%) cases of PJI were identified. In total, 4106 (18%) joint replacement operations were preceded by at least one course of antibiotics. The incidence of PJI for patients with preoperative use of oral antibiotics was 0.29% (12/4106), whereas for patients without antibiotic use it was 0.77% (146/19 065). A preoperative antibiotic course was associated with a reduced risk for subsequent PJI in the multivariable model (OR 0.40, 95% CI 0.22–0.73). Similar results were found in the propensity score matched material (OR 0.34, 95% CI 0.18–0.65).ConclusionsThe use of oral antibiotics before elective joint replacement surgery is common and has a potential effect on the subsequent risk for PJI. Nevertheless, indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though treatment of active infections remains an important way to prevent surgical site infections.     

The impact of preoperative bacteriuria on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow up

ObjectivesPatients who undergo elective joint replacement are traditionally screened and treated for preoperative bacteriuria to prevent periprosthetic joint infection (PJI). More recently, this practice has been questioned. The purpose of this study was to determine whether preoperative bacteriuria is associated with an increased risk of PJI.MethodsPatients who had undergone a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified from the hospital database (23 171 joint replacements, 10 200 hips, and 12 971 knees). The results of urine cultures taken within 90 days before the operation were obtained. Patients with subsequent PJI or superficial wound infection in a 1-year follow-up period were identified based on prospective infection surveillance. The association between bacteriuria and PJI was examined using a multivariable logistic regression model that included information on the operated joint, age, gender and the patients' chronic diseases.ResultsThe incidence of PJI was 0.68% (n = 158). Preoperative bacteriuria was not associated with an increased risk of PJI either in the univariate (0.51% versus 0.71%, OR 0.72, 95% CI 0.34–1.54) or in the multivariable (OR 0.82, 95% CI 0.38–1.77) analysis. There were no cases where PJI was caused by a pathogen identified in the preoperative urine culture. Results were similar for superficial infections.ConclusionsThere was no association between preoperative bacteriuria and postoperative surgical site infection. Based on these results, it seems that the preoperative screening and treatment of asymptomatic bacteriuria is not required.     

Origin and characteristics of haematogenous periprosthetic joint infection

ObjectivesRecognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI.MethodsConsecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and Mann–Whitney U tests were used, as appropriate.ResultsA total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1–417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n = 43), streptococci (n = 32), enterococci (n = 13), Gram-negative bacteria (n = 9) and coagulase-negative staphylococci (n = 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes).ConclusionsIn acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.     

Diagnosis of prosthetic joint infection by beadmill processing of a periprosthetic specimen

We report a microbiological process for the documentation of prosthetic joint infection (PJI). Intraoperative periprosthetic tissue samples from 92 consecutive patients undergoing revision surgery for PJI were submitted to mechanized beadmill processing: specimens were aseptically collected in polypropylene vials, filled with sterile water and glass beads and submitted to mechanized agitation with a beadmill. The documentation rate of PJI following culture on solid and liquid media was 83.7% and the contamination rate 8.7%. Final documentation was obtained after overnight culture for 51.9% of cases and with 7 days of broth culture for all documented cases.     

Microbiological diagnosis of prosthetic joint infections: a prospective evaluation of four bacterial culture media in the routine laboratory

The diagnosis of prosthetic joint infection (PJI) in the routine microbiology laboratory is labour-intensive, but semi-automated methods may be appropriate. We prospectively compared four microbiological culture methods on samples taken at prosthetic joint revision surgery. Automated BACTEC blood culture bottles and cooked meat enrichment broth were the most sensitive methods (87% and 83%, respectively, as compared with fastidious anaerobic broth (57%) and direct plates (39%)); all were highly specific (97–100%). To our knowledge, this is the first prospective study aimed at comparing culture methods in routine use in UK clinical laboratories for the diagnosis of PJI.     

Revision knee replacement for prosthetic joint infection: Epidemiology,clinical outcomes and health-economic considerations

Prosthetic joint infection (PJI) is a devastating complication of knee replacement surgery. Recent evidence has shown that the burden of disease is increasing as more and more knee replacement procedures are performed. The current incidence of revision total knee replacement (TKR) for PJI is estimated at 7.5 cases per 1000 primary joint replacement procedures at 10 years. Revision TKR for PJI is complex surgery, and is associated to a high rate of post-operative complications. The 5-year patient mortality is comparable to some common cancer diagnoses, and more than 15% of patients require re-revision by 10 years. Patient-reported outcome measures (PROMs) including joint function may be worse following revision TKR for PJI than for aseptic indications. The complexity and extended length of the treatment pathway for PJI places a significant burden on the healthcare system, highlighting it as an area for future research to identify the most clinically and cost-effective interventions.     

Gram-negative prosthetic joint infection: outcome of a debridement,antibiotics and implant retention approach. A large multicentre study

We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement >30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68–81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13–0.40; p <0.001), whereas chronic renal impairment predicted failure (aHR, 2.56; 95% CI, 1.14–5.77; p 0.0232). Our results confirm a 79% success rate in ciprofloxacin-susceptible GN-PJI treated with debridement, ciprofloxacin and implant retention. New therapeutic strategies are needed for ciprofloxacin-resistant PJI.     

Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy

Recent expert reviews recommend a conservative surgical strategy – debridement and irrigation, antibiotics and implant retention (DAIR) – for most early post-surgical prosthetic joint infections (PJI). However, differences exist in published series regarding success rates with DAIR, and the size of most series is small. In this prospective multicenter cohort study of early PJI managed by DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection was cured and the implant was salvaged with definite antimicrobial therapy. In 35 (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up. Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due to suspected or confirmed persistent infection. Infections due to methicillin-resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable was associated with treatment failure following multivariate analysis. Seventy-four per cent of patients who were successfully treated by DAIR and only 32.7% of the failures were able to walk without help or with one stick at the last follow-up visit (p <0.05). In conclusion, a substantial proportion of patients with an early PJI may be successfully treated with DAIR and definite antimicrobial therapy. In more than half of these, the infection can be cured. Since identification of factors associated with failure of DAIR is not simple, we recommend offering DAIR to most patients with early PJI.