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1.  Efficacy of a novel PCR- and microarray-based method in diagnosis of a prosthetic joint infection 
Acta Orthopaedica  2014;85(2):165-170.
Background and purpose
Polymerase chain reaction (PCR) methods enable detection and species identification of many pathogens. We assessed the efficacy of a new PCR and microarray-based platform for detection of bacteria in prosthetic joint infections (PJIs).
Methods
This prospective study involved 61 suspected PJIs in hip and knee prostheses and 20 negative controls. 142 samples were analyzed by Prove-it Bone and Joint assay. The laboratory staff conducting the Prove-it analysis were not aware of the results of microbiological culture and clinical findings. The results of the analysis were compared with diagnosis of PJIs defined according to the Musculoskeletal Infection Society (MSIS) criteria and with the results of microbiological culture.
Results
38 of 61 suspected PJIs met the definition of PJI according to the MSIS criteria. Of the 38 patients, the PCR detected bacteria in 31 whereas bacterial culture was positive in 28 patients. 15 of the PJI patients were undergoing antimicrobial treatment as the samples for analysis were obtained. When antimicrobial treatment had lasted 4 days or more, PCR detected bacteria in 6 of the 9 patients, but positive cultures were noted in only 2 of the 9 patients. All PCR results for the controls were negative. Of the 61 suspected PJIs, there were false-positive PCR results in 6 cases.
Interpretation
The Prove-it assay was helpful in PJI diagnostics during ongoing antimicrobial treatment. Without preceding treatment with antimicrobials, PCR and microarray-based assay did not appear to give any additional information over culture.
doi:10.3109/17453674.2014.889978
PMCID: PMC3967259  PMID: 24564748
2.  Prosthetic Joint Infection in Patients with Rheumatoid Arthritis: An Outcome Analysis Compared with Controls 
PLoS ONE  2013;8(8):e71666.
Background
Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of prosthetic joint infection (PJI) after hip or knee replacement. However, little information is available on the demographic data, outcome of treatment and prognostic factors in RA patients when compared to those in non-RA patients.
Methods/Principal Findings
We performed a retrospective cohort analysis of all cases of PJI that were treated at our institution between 2002 and 2008. Of 346 episodes of PJI during the study period, 46 (13.3%) occurred in patients with RA. Compared to the non-RA cohort, RA patients with PJI were female predominant (74% vs 27%, p<0.001), younger (median age, 51 vs 63 years, p<0.001) and developed infection earlier (median joint age, 72 vs 128 days, p<0.001). The 2-year survival rate free of treatment failure was lower in RA patients with PJI episodes either treated with débridement (22% vs 52%, p = 0.002) or two-stage exchange (78% vs 95%, p = 0.004). A longer duration of symptoms before débridement surgery (median, 11 vs 5 days, p = 0.015), and absence of antibiotics in bone cement for two-stage exchange (relative risk, 8.0; p = 0.02) were associated with treatment failure in patients with RA.
Discussion
The outcome of PJI in RA patients was generally worse than that in non-RA patients. Risk of treatment failure increased in the setting of delayed débridement and two-stage exchange without the use of antibiotic-impregnated bone cement. These findings highlight the importance of vigilant monitoring and aggressive treatment for PJI in RA patients.
doi:10.1371/journal.pone.0071666
PMCID: PMC3753295  PMID: 23990969
3.  Prior Use of Antimicrobial Therapy is a Risk Factor for Culture-negative Prosthetic Joint Infection 
Background
Clinical characteristics and control of the infection of patients with culture-negative (CN) prosthetic joint infection (PJI) have not been well assessed. Prior use of antimicrobial therapy has been speculated but not proven as a risk factor for CNPJI.
Questions/purposes
We therefore determined whether prior use of antimicrobial therapy, prior PJI, and postoperative wound healing complications were associated with CN PJI.
Methods
We performed a retrospective case-control study of 135 patients with CN PJI treated between January 1, 1985, and December 31, 2000 matched with 135 patients with culture-positive (CP) PJIs (control patients) during the study period. The time to failure of therapy compared between cases and control patients using a Kaplan-Meier analysis.
Results
The use of prior antimicrobial therapy and postoperative wound drainage after index arthroplasty were associated with increased odds of PJI being culture-negative (odds ratio, 4.7; 95% CI, 2.8–8.1 and odds ratio, 3.5; 95% CI, 1.5–8.1, respectively). The percent (± SE) cumulative incidence free of treatment failure at 2 years followup was similar for CN and CP PJI: 75% (± 4%) and 79% (± 4%), respectively.
Conclusions
Prior antimicrobial therapy and postoperative wound drainage were associated with an increased risk of negative cultures among patients with PJI. Physicians should critically evaluate the need for antimicrobial therapy before establishing a microbiologic diagnosis of PJI in patients with suspected PJI.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1338-0
PMCID: PMC2895855  PMID: 20401555
4.  2-stage revision recommended for treatment of fungal hip and knee prosthetic joint infections 
Acta Orthopaedica  2013;84(6):517-523.
Background and purpose
Fungal prosthetic joint infections are rare and difficult to treat. This systematic review was conducted to determine outcome and to give treatment recommendations.
Patients and methods
After an extensive search of the literature, 164 patients treated for fungal hip or knee prosthetic joint infection (PJI) were reviewed. This included 8 patients from our own institutions.
Results
Most patients presented with pain (78%) and swelling (65%). In 68% of the patients, 1 or more risk factors for fungal PJI were found. In 51% of the patients, radiographs showed signs of loosening of the arthroplasty. Candida species were cultured from most patients (88%). In 21% of all patients, fungal culture results were first considered to be contamination. There was co-infection with bacteria in 33% of the patients. For outcome analysis, 119 patients had an adequate follow-up of at least 2 years. Staged revision was the treatment performed most often, with the highest success rate (85%).
Interpretation
Fungal PJI resembles chronic bacterial PJI. For diagnosis, multiple samples and prolonged culturing are essential. Fungal species should be considered to be pathogens. Co-infection with bacteria should be treated with additional antibacterial agents.
We found no evidence that 1-stage revision, debridement, antibiotics, irrigation, and retention (DAIR) or antifungal therapy without surgical treatment adequately controls fungal PJI. Thus, staged revision should be the standard treatment for fungal PJI. After resection of the prosthesis, we recommend systemic antifungal treatment for at least 6 weeks—and until there are no clinical signs of infection and blood infection markers have normalized. Then reimplantation can be performed.
doi:10.3109/17453674.2013.859422
PMCID: PMC3851663  PMID: 24171675
5.  INCIDENCE, SECULAR TRENDS AND OUTCOMES OF PROSTHETIC JOINT INFECTION (PJI): A POPULATION BASED STUDY, OLMSTED COUNTY, MINNESOTA, 1969 – 2007 
Context
The epidemiology of prosthetic joint infection (PJI) in a population based cohort has not been studied in the United States.
Objectives
To provide an accurate assessment of the true incidence, secular trends, clinical manifestations, microbiology and treatment outcomes of PJI in a population based cohort.
Design
Historical cohort study
Setting
Olmsted County, Minnesota, United States of America.
Participants
Residents who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) between 1/ 1/ 1969 and 12/ 31/ 2007.
Methods
Incidence rates and trends in PJI were assessed using the Kaplan Meier method and log-rank test, as were treatment outcomes among PJI cases.
Results
7375 THA or TKA were implanted in residents of Olmsted County during the study period. Seventy five discrete joints in 70 individuals developed PJI, during a mean(+/− SD) follow up of 6.8 (+/− 6.1) years. The cumulative incidence of PJI was 0.5%, 0.8% and 1.4% after 1, 5 and 10 years following arthroplasty, respectively. Overall, the rate of survival free of clinical failure after treatment of PJI was 76.8 % ( 95% CI: 64.3 – 85.2) and 65.2 % ( 95% CI: 33.1 – 76.2) at 3 years and 5 years, respectively. The incidence and treatment outcomes did not significantly differ by decade of implantation, patient age at implantation, gender or joint location.
Conclusions
The incidence of PJI is relatively low in a population based cohort, and is a function of age of the prosthesis. Incidence trends and outcomes have not significantly changed over the past forty years.
doi:10.1086/668421
PMCID: PMC3602045  PMID: 23143357
6.  Current management of prosthetic joint infections in adults: results of an Emerging Infections Network survey 
There is a dearth of guidance on the management of prosthetic joint infections (PJIs), in particular because of the lack of high-quality evidence for optimal antibiotics. Thus, we designed a nine-question survey of current practices and preferences among members of the Emerging Infections Network, a CDC-sponsored network of infectious diseases physicians, which was distributed in May 2012. In total, 556 (47.2%) of 1178 network members responded. As first-line antibiotic choice for MSSA PJI, 59% of responders indicated oxacillin/nafcillin, 33% cefazolin and 7% ceftriaxone; the commonest alternative was cefazolin (46%). For MRSA PJI, 90% preferred vancomycin, 7% daptomycin and 0.8% ceftaroline; the commonest alternative was daptomycin (65%). Antibiotic selection for coagulase-negative staphylococci varied depending on meticillin susceptibility. For staphylococcal PJIs with retained hardware, most providers would add rifampicin. Propionibacterium is usually treated with vancomycin (40%), penicillin (23%) or ceftriaxone (17%). Most responders thought 10–19% of all PJIs were culture-negative. Culture-negative PJIs of the lower extremities are usually treated with a vancomycin/fluoroquinolone combination, and culture-negative shoulder PJIs with vancomycin/ceftriaxone. The most cited criteria for selecting antibiotics were ease of administration and the safety profile. A treatment duration of 6–8 weeks is preferred (by 77% of responders) and is mostly guided by clinical response and inflammatory markers. Ninety-nine percent of responders recommend oral antibiotic suppression (for varying durations) in patients with retained hardware. In conclusion, there is considerable variation in treatment of PJIs both with identified pathogens and those with negative cultures. Future studies should aim to identify optimum treatment strategies.
doi:10.1016/j.ijantimicag.2012.10.023
PMCID: PMC3572796  PMID: 23312602
Prosthetic joint infection; Osteomyelitis; Staphylococcus aureus; Antibiotic; Treatment
7.  Prosthetic joint infection due to Salmonella species: a case series 
BMC Infectious Diseases  2014;14(1):633.
Background
Prosthetic joint infection (PJI) due to Salmonella is rare. Numerous outbreaks of Salmonella have been reported throughout the United States in the last decade. We reviewed and analyzed cases of Salmonella PJI seen at our institution.
Methods
The medical records of all patients diagnosed with a Salmonella PJI between 1969–2013 were reviewed. Patients were followed till death, treatment failure or loss to follow-up.
Results
Six patients of Salmonella PJI were identified during the 44 year study period. Five were male; median age was 63.5 years (range 52–76). Five patients were immunodeficient. Five had a total hip arthroplasty infection, while one had a total knee arthroplasty infection. Median prosthesis age at the time of diagnosis of first episode of Salmonella PJI was 5 years (range 4 months-9 years). Four presented with fever and constitutional signs within two weeks of symptom onset. Two patients each had gastrointestinal symptoms and Salmonella bacteremia. Salmonella enterica serovar Enteritidis was the most common organism isolated (4 patients). None were Salmonella enterica serovar Typhi. Initial management included aspiration and antimicrobial therapy only (3), debridement and component retention (1) and two-staged exchange (2). All four patients treated without resection failed treatment a median of 2.5 months (range 2–11) after diagnosis and required resection arthroplasty. All six patients who underwent prosthesis removal (and exchange or arthrodesis) had successful outcome with a median duration of follow-up of 11 years (range 4–21). Three of these received oral antimicrobial therapy for a median duration eight weeks (range 4–8) and three received parenteral antimicrobial therapy for a median duration of six weeks (range 4–6).
Conclusions
The increase in Salmonella outbreaks does not seem to lead to increased Salmonella PJI. PJIs due to Salmonella remain rare, and the presentation is often acute with fever. It frequently occurs in immunocompromised patients. In our patient population, removal of prosthesis with or without reimplantation, along with 4–6 weeks of effective parenteral antimicrobial therapy was most often associated with successful eradication of infection.
doi:10.1186/s12879-014-0633-x
PMCID: PMC4258011  PMID: 25424009
Salmonella; Prosthetic joint infections; Arthroplasty
8.  Risk factors for total joint arthroplasty infection in patients receiving tumor necrosis factor α-blockers: a case-control study 
Arthritis Research & Therapy  2010;12(4):R145.
Introduction
The objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)α-blockers, through the French RATIO registry and a case-control study.
Methods
Cases were TJA infections during TNFα-blocker treatments. Each case was compared to two controls (with TJA and TNFα-blocker therapy, but without TJA infection) matched on age (±15 years), TJA localization, type of rheumatic disorder and disease duration (±15 years). Statistical analyses included univariate and multivariate analyses with conditional logistic regression.
Results
In the 20 cases (18 rheumatoid arthritis), TJA infection concerned principally the knee (n = 12, 60%) and the hip (n = 5, 25%). Staphylococcus was the more frequent microorganism involved (n = 15, 75%). Four patients (20%) were hospitalized in an intensive care unit and two died from infection. Eight cases (40%) versus 5 controls (13%) had undergone primary TJA or TJA revision for the joint subsequently infected during the last year (P = 0.03). Of these procedures, 5 cases versus 1 control were performed without withdrawing TNFα-blockers (P = 0.08). In multivariate analysis, predictors of infection were primary TJA or TJA revision for the joint subsequently infected within the last year (odds ratio, OR = 88.3; 95%CI 1.1-7,071.6; P = 0.04) and increased daily steroid intake (OR = 5.0 per 5 mg/d increase; 1.1-21.6; P = 0.03). Case-control comparisons showed similar distribution between TNFα-blockers (P = 0.70).
Conclusions
In patients receiving TNFα-blockers, TJA infection is rare but potentially severe. Important risk factors are primary TJA or TJA revision within the last year, particularly when TNFα-blockers are not interrupted before surgery, and the daily steroid intake.
doi:10.1186/ar3087
PMCID: PMC2945039  PMID: 20637100
9.  Role of Universal 16S rRNA Gene PCR and Sequencing in Diagnosis of Prosthetic Joint Infection 
Journal of Clinical Microbiology  2012;50(3):583-589.
The etiological diagnosis of prosthetic joint infection (PJI) requires the isolation of microorganisms from periprosthetic samples. Microbiological cultures often yield false-positive and false-negative results. 16S rRNA gene PCR combined with sequencing (16SPCR) has proven useful for diagnosing various infections. We performed a prospective study to compare the utility of this approach with that of culture to diagnose PJI using intraoperative periprosthetic samples. We analyzed 176 samples from 40 patients with PJI and 321 samples from 82 noninfected patients using conventional culture and 16SPCR. Three statistical studies were undertaken following a previously validated mathematical model: sample-to-sample analysis, calculation of the number of samples to be studied, and calculation of the number of positive samples necessary to diagnose PJI. When only the number of positive samples is taken into consideration, a 16SPCR-positive result in one sample has good specificity and positive predictive value for PJI (specificity, 96.3%; positive predictive value, 91.7%; and likelihood ratio [LR], 22), while 3 positive cultures with the same microorganism are necessary to achieve similar specificity. The best combination of results for 16SPCR was observed when 5 samples were studied and the same microorganism was detected in 2 of them (sensitivity, 94%; specificity, 100%; and LR, 69.62). The results for 5 samples with 2 positive cultures were 96% and 82%, respectively, and the likelihood ratio was 1.06. 16SPCR is more specific and has a better positive predictive value than culture for diagnosis of PJI. A positive 16SPCR result is largely suggestive of PJI, even when few samples are analyzed; however, culture is generally more sensitive.
doi:10.1128/JCM.00170-11
PMCID: PMC3295163  PMID: 22170934
10.  Early prosthetic joint infections treated with debridement and implant retention 
Acta Orthopaedica  2012;83(3):227-232.
Background and purpose
Debridement and retention of the prosthesis is often attempted to treat early prosthetic joint infection (PJI). However, previous studies have found inconsistent results, with success rates ranging from 21% to 100%, and little has been written in the literature about hip function. We have therefore analyzed the clinical and functional outcome of early PJIs treated with this procedure.
Patients and methods
38 patients with early PJI after primary hip arthroplasty who were treated with debridement and retention of the implant between 1998 and 2005 were studied prospectively, with a median follow-up time of 4 (0.8–10) years. Early infection was defined as that which occurred within 4 weeks of index arthroplasty. The primary outcome measure was infection control. Functional outcome was assessed with the Harris hip score.
Results
27 of 38 patients were successfully treated, with no signs of infection or continued antibiotic treatment at the latest follow-up. Median Harris hip score was 86 (47–100) points. In 9 of the 11 patients for whom treatment failed, infection was successfully treated with 1-stage or 2-stage reimplantation or resection. Intraoperative cultures were positive in 36 hips, and the most frequently isolated organisms were Staphylococcus aureus and coagulase-negative staphylococci (CoNS). 15 infections were polymicrobial, and only 8 of them were successfully treated with debridement and retention of the implant.
Interpretation
Our data suggest that debridement and retention of the prosthesis is a reasonable treatment option in early PJI after primary hip arthroplasty, with satisfactory functional results.
doi:10.3109/17453674.2012.678801
PMCID: PMC3369146  PMID: 22489892
11.  Low Rate of Infection Control in Enterococcal Periprosthetic Joint Infections 
Background
Enterococcal periprosthetic joint infections (PJIs) are rare after joint arthroplasty. These cases are usually reported in series of PJIs caused by other pathogens. Because few studies have focused only on enterococcal PJIs, management and control of infection of these cases have not yet been well defined.
Questions/Purposes
We asked (1) what is the proportion of enterococcal PJI in our institutes; and (2) what is the rate of infection control in these cases?
Methods
We respectively identified 22 and 14 joints with monomicrobial and polymicrobial PJI, respectively, caused by enterococcus. The diagnosis of PJI was made based on the presence of sinus tract or two positive intraoperative cultures. PJI was also considered in the presence of one positive intraoperative culture and abnormal serology. We determined the proportion of enterococcal PJI and management and control of infection in these cases. Minimum followup was 1.5 years (mean, 3.2 years).
Results
The proportion of monomicrobial enterococcal PJI was 2.3% (22 of 955 cases of PJI). Mean number of surgeries was two (range, 1–4). Initial irrigation and débridement was performed in 10 joints and eight patients needed reoperation. Seven of the 16 joints were initially managed using two-stage exchange arthroplasty and did not need further operation. Six patients had a definitive resection arthroplasty. Salvage surgeries (fusion and above-knee amputation) were performed in three cases (8%). The infection was ultimately controlled in 32 of the 36 patients.
Conclusions
Management of enterococcal PJI is challenging and multiple operations may need to be performed to control the infection.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2374-8
PMCID: PMC3442013  PMID: 22552769
12.  Targeted Use of Vancomycin as Perioperative Prophylaxis Reduces Periprosthetic Joint Infection in Revision TKA 
Background
The role of vancomycin in surgical antimicrobial prophylaxis and high-risk patients who are most likely to benefit remains unclear.
Questions/purposes
We determined the impact of targeted use of vancomycin on (1) the incidence of periprosthetic joint infection (PJI); and (2) the incidence of PJI from methicillin-resistant organisms in patients undergoing revision total knee arthroplasty (TKA) at our institution.
Methods
In an effort to reduce PJI rates, we added vancomycin to cefazolin as surgical antimicrobial prophylaxis for patients undergoing revision TKA in October 2010. Internal data indicated a high rate of PJI in revision TKA and in particular PJI resulting from methicillin-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). We retrospectively reviewed infection control surveillance data on 414 revision TKAs performed between July 2008 and June 2012 (fiscal years 2009–2012).
Results
The overall rate of PJI in fiscal years 2009–2010 among 190 patients undergoing revision TKA was 7.89%. After the change in surgical antimicrobial prophylaxis, there was a significant reduction in PJI among patients undergoing revision TKA in fiscal years 2011–2012 to 3.13% (p = 0.046). In particular, we observed a reduction in PJI resulting from methicillin-resistant organisms over this same time period, from 4.21% to 0.89% (p = 0.049).
Conclusions
Targeted use of vancomycin in patients undergoing revision TKA was effective in reducing the rate of PJI and PJI resulting from methicillin-resistant organisms in an institution with a high baseline rate of PJI due to MRSA and MRSE. Identification of high-risk subgroups of patients within a surgical population can help target infection prevention strategies to those who are most likely to benefit and thus minimize potential risks (eg, selection of resistant organisms, adverse drug events) associated with broader application of such an intervention.
Level of Evidence
Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-013-3029-0
PMCID: PMC3889430  PMID: 23645338
13.  Periprosthetic joint infection: Current concept 
Indian Journal of Orthopaedics  2013;47(1):10-17.
Periprosthetic joint infection (PJI) is one of the most devastating and costly complications following total joint arthroplasty (TJA). Diagnosis and management of PJI is challenging for surgeons. There is no “gold standard” for diagnosis of PJI, making distinction between septic and aseptic failures difficult. Additionally, some of the greatest difficulties and controversies involve choosing the optimal method to treat the infected joint. Currently, there is significant debate as to the ideal treatment strategy for PJI, and this has led to considerable international variation in both surgical and nonsurgical management of PJI. In this review, we will discuss diagnosis and management of PJI following TJA and highlight some recent advances in this field.
doi:10.4103/0019-5413.106884
PMCID: PMC3601222  PMID: 23531512
Periprosthetic joint infection; total joint arthroplasty; diagnosis and treatment of periprosthetic joint infection
14.  Clinical Characteristics and Outcomes of Prosthetic Joint Infection Caused by Small Colony Variant Staphylococci 
mBio  2014;5(5):e01910-14.
ABSTRACT
Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with prospective testing of archived sonicate fluid samples. SCVs were defined using two-investigator review. Treatment failure was defined as (i) subsequent revision surgery for any reason, (ii) PJI after the index surgery, (iii) prosthesis nonreimplantation due to ongoing infection, or (iv) amputation of the affected limb. There were 38 subjects (34%) with SCVs and 75 (66%) with only normal-phenotype (NP) bacteria. Subjects with SCVs were more likely to have been on chronic antimicrobials prior to surgery (P = 0.048), have had prior surgery for PJI (P = 0.03), have had a longer duration of symptoms (P = 0.0003), and have had a longer time since joint implantation (P = 0.007), compared to those with only NP bacteria. Over a median follow-up of 30.6 months, 9 subjects (24%) with SCVs and 23 (32%) with only NP bacteria experienced treatment failure (P = 0.51). Subjects infected with Staphylococcus aureus were more likely to fail than were those infected with Staphylococcus epidermidis (hazard ratio [HR], 4.03; 95% confidence interval [CI], 1.80 to 9.04). While frequently identified in subjects with PJI and associated with several potential predisposing factors, SCVs were not associated with excess treatment failure compared to NP infections in this study, where they were primarily managed with two-stage arthroplasty exchange.
IMPORTANCE
Bacteria with the small colony variant (SCV) phenotype are described in small case series as causing persistent or relapsing infection, but there are insufficient data to suggest that they should be managed differently than infection with normal-phenotype bacteria. In an effort to investigate the clinical importance of this phenotype, we determined whether SCVs were present in biofilms dislodged from the surfaces of arthroplasties of patients with staphylococcal prosthetic joint infection and assessed the clinical outcomes associated with detection of SCVs. We found that prosthetic joint infection caused by SCV staphylococci was associated with a longer duration of symptoms and more prior treatment for infection but not with an increased rate of treatment failure, compared to infection caused by normal-phenotype staphylococci.
doi:10.1128/mBio.01910-14
PMCID: PMC4196237  PMID: 25271290
15.  Treatment of acute periprosthetic infections with prosthesis retention: Review of current concepts 
World Journal of Orthopedics  2014;5(5):667-676.
Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro’s and con’s should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or coagulase negative). If DAIR treatment is unsuccessful, the following treatment option should be based on the patient health status and his or her expectations. For the best functional outcome, one- or two-stage revision should be performed after DAIR failure. In conclusion, DAIR is the obvious choice for treatment of acute PJI, with good success rates in selected patients.
doi:10.5312/wjo.v5.i5.667
PMCID: PMC4133475  PMID: 25405096
Arthroplasty; Prosthesis; Infection; Periprosthetic joint infection; Retention; Debridement antibiotics and implant retention; Debridement; Acute
16.  Preoperative Anemia in Total Joint Arthroplasty: Is It Associated with Periprosthetic Joint Infection? 
Background
Anemia is common in patients undergoing total joint arthroplasty (TJA). Numerous studies have associated anemia with increased risk of infection, length of hospital stay, and mortality in surgical populations. However, it is unclear whether and to what degree preoperative anemia in patients undergoing TJA influences postoperative periprosthetic joint infection (PJI) and mortality.
Questions/Purposes
We therefore (1) determined the incidence of preoperative anemia in patients undergoing TJA; (2) assessed the possible association between preoperative anemia and subsequent PJI; and (3) explored the relationship between preoperative anemia with postoperative mortality.
Methods
We identified 15,722 patients who underwent TJA from January 2000 to June 2007. Anemia was defined as hemoglobin < 12 g/dL in women and hemoglobin < 13 g/dL in men. We determined the effect of preoperative anemia, demographics, and comorbidities on postoperative complications.
Results
Of the 15,222 patients, 19.6% presented with preoperative anemia. PJI occurred more frequently in anemic patients at an incidence of 4.3% in anemic patients compared with 2% in nonanemic patients. Thirty-day (0.4%), 90-day (0.6%), and 1-year (1.8%) mortality rates were not higher in patients with preoperative anemia. Forty-four percent of anemic patients received an allogenic transfusion compared with only 13.4% of nonanemic patients. Anemic patients had increased hospital stays averaging 4.3 days compared with 3.9 days in nonanemic patients. Anemia did not predict cardiac complications.
Conclusion
Our data demonstrate that preoperative anemia is associated with development of subsequent PJI. Preoperative anemia was not associated with 30-day, 60-day, or 1-year mortality in this cohort.
Level of Evidence
Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2435-z
PMCID: PMC3442010  PMID: 22773393
17.  Toll-Like Receptor 2 in Serum: a Potential Diagnostic Marker of Prosthetic Joint Infection? 
Journal of Clinical Microbiology  2014;52(2):620-623.
Prosthetic joint infection (PJI) is a severe complication of arthroplasty and is still lacking diagnostic gold standards. PJI patients display high Toll-like receptor 2 (TLR2) serum levels, correlating with canonical inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α], and IL-1). Therefore, TLR2 serum levels could be considered a new potential diagnostic tool in the early detection of PJI.
doi:10.1128/JCM.02727-13
PMCID: PMC3911304  PMID: 24478497
18.  Outcomes of Total Joint Arthroplasty in HIV Patients 
The Iowa Orthopaedic Journal  2014;34:102-106.
Background
Advancement in human immunodeficiency virus (HIV) therapies has increased life expectancy. The need for joint replacement is expected to increase as this population develops degenerative changes from aging and avascular necrosis (AVN). Studies have shown a higher risk of peri-prosthetic joint infections (PJI) in HIV patients. However, these studies include a high percentage of hemophiliacs, which may be a confounding variable. With the advent of highly active anti-retroviral therapy (HAART) and evolving HIV demographics, we hypothesize the rate of PJIs in HIV patients are comparable to the general population.
Methods
We performed a retrospective cohort study using prospectively collected data from our arthroplasty database. We identified 24 HIV patients that underwent 31 primary hip and one primary knee arthroplasty between July 1, 2000 and September 30, 2012. Mean age was 50 years (range 31-74). Mean follow-up was 14 months (range 1.5-60).
Results
There were no PJIs in our HIV population. All HIV patients were non-hemophiliacs on HAART. Thirty-one total hip arthroplasties (THA) and one total knee arthroplasty were performed. Twenty-one HIV patients underwent THA for AVN. Eight patients had bilateral AVN. One patient needed revision for aseptic loosening. The mean CD4 count was 647 (194-1193). Mean viral load was undetectable in 19 patients and unavailable in five.
Conclusions
Our HIV population had a lower rate of PJI compared to infection rates in prior literature. Despite our limited patient population, our data suggests that well controlled HIV patients on HAART therapy with undetectable viral loads and CD4 >200 are at similar risk of PJI as the average population.
PMCID: PMC4127742  PMID: 25328467
19.  Corynebacterium Prosthetic Joint Infection 
Journal of Clinical Microbiology  2012;50(5):1518-1523.
Identification of Corynebacterium species may be challenging. Corynebacterium species are occasional causes of prosthetic joint infection (PJI), but few data are available on the subject. Based on the literature, C. amycolatum, C. aurimucosum, C. jeikeium, and C. striatum are the most common Corynebacterium species that cause PJI. We designed a rapid PCR assay to detect the most common human Corynebacterium species, with a specific focus on PJI. A polyphosphate kinase gene identified using whole-genome sequence was targeted. The assay differentiates the antibiotic-resistant species C. jeikeium and C. urealyticum from other species in a single assay. The assay was applied to a collection of human Corynebacterium isolates from multiple clinical sources, and clinically relevant species were detected. The assay was then tested on Corynebacterium isolates specifically associated with PJI; all were detected. We also describe the first case of C. simulans PJI.
doi:10.1128/JCM.06439-11
PMCID: PMC3347109  PMID: 22337986
20.  Diagnosis of periprosthetic infection following total hip arthroplasty – evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection 
Background
The correct diagnosis of a prosthetic joint infection (PJI) is crucial for adequate surgical treatment. The detection may be a challenge since presentation and preoperative tests are not always obvious and precise. This prospective study was performed to evaluate a variety of pre- and intraoperative investigations. Furthermore a detailed evaluation of concordance of each preoperative diagnosis was performed, together with a final diagnosis to assess the accuracy of the pre-operative assumption of PJI.
Methods
Between 01/2005 and 02/2007, a prospective analysis was performed in 50 patients, who had a two stage revision because of assumed PJI. Based on clinical presentation, radiography, haematological screening, or early failure, infection was assumed and a joint aspiration was performed. Depending upon these findings, a two stage revision was performed, with intra-operative samples for culture and histological evaluation obtained. Final diagnosis of infection was based upon the interpretation of the clinical presentation and the pre- and intraoperative findings.
Results
In 37 patients a positive diagnosis of PJI could be made definitely. The histopathology yielded the highest accuracy (0.94) in identification of PJI and identified 35 of 37 infections (sensitivity 0.94, specificity 0.94, positive-/negative predictive value 0.97/0.86). Intra-operative cultures revealed sensitivities, specificities, positive-/negative predictive values and accuracy of 0.78, 0.92, 0.96, 0.63 and 0.82. These values for blood screening tests were 0.95, 0.62, 0.88, 0.80, and 0.86 respectively for the level of C-reactive protein, and 0.14, 0.92, 0.83, 0.29 and, 0.34 respectively for the white blood-cell count. The results of aspiration were 0.57, 0.5, 0.78, 0.29, and 0.54.
Conclusion
The detection of PJI is still a challenge in clinical practice. The histopathological evaluation emerges as a highly practical diagnostic tool in detection of PJI. Furthermore, we found a discrepancy between the pre-operative suspicion of PJI and the final post-operative diagnosis, resulting in a slight uncertainty in whether loosening is due to bacterial infection or not. The variation in accuracy of the single tests may influence the detection of PJI. Level of Evidence: Diagnostic Level I.
doi:10.1186/1749-799X-3-31
PMCID: PMC2492844  PMID: 18644107
21.  Risk Factors for Periprosthetic Joint Infection after Total Hip Arthroplasty and Total Knee Arthroplasty in Chinese Patients 
PLoS ONE  2014;9(4):e95300.
Purpose
The purpose of this hospital-based case–control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.
Method
From January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs).
Results
Demographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77–16.97; p = 0.003), age (65–75 vs. 45–65 years) (OR = 3.36, 95% CI: 1.30–8.69; p = 0.013), BMI (≥28 vs. 18.5–28 kg/m2) (OR = 2.77, 95% CI: 1.20–6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13–6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06–8.23; p = 0.039).
Conclusion
Patients with diabetes, older age, BMI of ≥28 kg/m2 and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.
doi:10.1371/journal.pone.0095300
PMCID: PMC3991645  PMID: 24748009
22.  Optimization of Periprosthetic Culture for Diagnosis of Propionibacterium acnes Prosthetic Joint Infection▿ 
Journal of Clinical Microbiology  2011;49(7):2490-2495.
Propionibacterium acnes is increasingly recognized as an important agent of prosthetic joint infection (PJI). However, the optimum culture conditions for recovery of this organism from PJI specimens have not been determined. By applying a prolonged 28-day culture incubation to all periprosthetic specimens received for bacterial culture from 198 revision arthroplasty procedures, we retrospectively determined that a 13-day culture incubation period is necessary for the recovery of P. acnes from patients with PJI. Incubation beyond this period was associated with increasing recovery of nondiagnostic isolates: 21.7% of P. acnes isolates believed to be clinically unimportant were recovered after 13 days of incubation. Importantly, a diagnosis of P. acnes PJI would have been missed in 29.4% of patients had extended culture incubation been applied only to anaerobic culture media. Although specimens from P. acnes PJIs were more commonly associated with the presence of ≥2 culture media positive for growth, acute inflammation (≥5 neutrophils/high-power field) was observed in only 40% of patients with PJIs that had more than one specimen submitted for bacterial culture. These results support the need for a minimum culture incubation period of 13 days to be applied to both aerobic and anaerobic culture media for all periprosthetic specimens. Optimal recovery of infecting organisms from PJI specimens will be an important component in generating a universal definition for PJI due to indolent agents of infection, such as P. acnes.
doi:10.1128/JCM.00450-11
PMCID: PMC3147880  PMID: 21543562
23.  Use of an automated blood culture system (BD BACTEC™) for diagnosis of prosthetic joint infections: easy and fast 
BMC Infectious Diseases  2014;14:233.
Background
For the diagnosis of prosthetic joint infection (PJI) automated BACTEC™ blood culture bottle methods have comparable sensitivity, specificity and a shorter time to positivity than traditional cooked meat enrichment broth methods. We evaluate the culture incubation period required to maximise sensitivity and specificity of microbiological diagnosis, and the ability of BACTEC™ to detect slow growing Propionibacteria spp.
Methods
Multiple periprosthetic tissue samples taken by a standardised method from 332 patients undergoing prosthetic joint revision arthroplasty were cultured for 14 days, using a BD BACTEC™ instrumented blood culture system, in a prospective study from 1st January to 31st August 2012. The “gold standard” definition for PJI was the presence of at least one histological criterion, the presence of a sinus tract or purulence around the device. Cases where > =2 samples yielded indistinguishable isolates were considered culture-positive. 1000 BACTEC™ bottle cultures which were negative after 14 days incubation were sub-cultured for Propionibacteria spp.
Results
79 patients fulfilled the definition for PJI, and 66 of these were culture-positive. All but 1 of these 66 culture-positive cases of PJI were detected within 3 days of incubation. Only one additional (clinically-insignificant) Propionibacterium spp. was identified on terminal subculture of 1000 bottles.
Conclusions
Prolonged microbiological culture for 2 weeks is unnecessary when using BACTEC™ culture methods. The majority of clinically significant organisms grow within 3 days, and Propionibacteria spp. are identified without the need for terminal subculture. These findings should facilitate earlier decisions on final antimicrobial prescribing.
doi:10.1186/1471-2334-14-233
PMCID: PMC4101863  PMID: 24885168
BACTEC™; Prosthetic joint infection; Culture; Propionibacteria
24.  Laboratory and Clinical Characteristics of Staphylococcus lugdunensis Prosthetic Joint Infections▿  
Journal of Clinical Microbiology  2010;48(5):1600-1603.
Staphylococcus lugdunensis is a coagulase-negative staphylococcus that has several similarities to Staphylococcus aureus. S. lugdunensis is increasingly being recognized as a cause of prosthetic joint infection (PJI). The goal of the present retrospective cohort study was to determine the laboratory and clinical characteristics of S. lugdunensis PJIs seen at the Mayo Clinic in Rochester, MN, between 1 January 1998 and 31 December 2007. Kaplan-Meier survival methods and Wilcoxon sum-rank analysis were used to determine the cumulative incidence of treatment success and assess subset comparisons. There were 28 episodes of S. lugdunensis PJIs in 22 patients; half of those patients were females. Twenty-five episodes (89%) involved the prosthetic knee, while 3 (11%) involved the hip. Nine patients (32%) had an underlying urogenital abnormality. Among the 28 isolates in this study tested by agar dilution, 24 of 28 (86%) were oxacillin susceptible. Twenty of the 21 tested isolates (95%) lacked mecA, and 6 (27%) of the 22 isolates tested produced β-lactamase. The median durations of parenteral β-lactam therapy and vancomycin therapy were 38 days (range, 23 to 42 days) and 39 days (range, 12 to 60 days), respectively. The cumulative incidences of freedom from treatment failure (standard deviations) at 2 years were 92% (±7%) and 76% (±12%) for episodes treated with a parenteral β-lactam and vancomycin, respectively (P = 0.015). S. lugdunensis is increasingly being recognized as a cause of PJIs. The majority of the isolates lacked mecA. Episodes treated with a parenteral β-lactam antibiotic appear to have a more favorable outcome than those treated with parenteral vancomycin.
doi:10.1128/JCM.01769-09
PMCID: PMC2863876  PMID: 20181900
25.  Success After Treatment of Periprosthetic Joint Infection: A Delphi-based International Multidisciplinary Consensus 
Background
The lack of agreement regarding what constitutes successful treatment for periprosthetic joint infections (PJI) makes it difficult to compare the different strategies of management that are used in clinical practice and in research studies.
Questions/purposes
The aims of this study were to create a consensus definition for success after PJI treatment, and to provide a universal, multidimensional framework for reporting of studies regarding PJI treatment.
Methods
A two-round basic Delphi method was used to reach a consensus definition. We invited 159 international experts (orthopaedic surgeons, infectious disease specialists, and clinical researchers) from 17 countries to participate; 59 participated in the first round, and 42 participated in the second round. The final definition consisted of all statements that achieved strong agreement (80% or greater of participants considering a criterion relevant for defining success).
Results
The consensus definition of a successfully treated PJI is: (1) infection eradication, characterized by a healed wound without fistula, drainage, or pain, and no infection recurrence caused by the same organism strain; (2) no subsequent surgical intervention for infection after reimplantation surgery; and (3) no occurrence of PJI-related mortality (by causes such as sepsis, necrotizing fasciitis). The Delphi panel agreed to defining midterm results as those reported 5 or more years after the definitive PJI surgery, and long-term results as those reported 10 or more years after surgery. Although no consensus was reached on the definition of short-term results, 71% of the participants agreed that 2 years after the definitive PJI surgery is acceptable to define it.
Conclusions
This multidimensional definition of success after PJI treatment may be used to report and compare results of treatment of this catastrophic complication.
Level of Evidence
Level V, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Electronic supplementary material
The online version of this article (doi:10.1007/s11999-013-2866-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s11999-013-2866-1
PMCID: PMC3676607  PMID: 23440616

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