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1.  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
2.  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
3.  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
4.  Polymicrobial Prosthetic Joint Infections: Risk Factors and Outcome 
Limited data are available regarding the risk factors and outcome of polymicrobial prosthetic joint infection (PJIs) when compared with monomicrobial PJI. Between January 1998 and November 2006, we retrospectively identified 34 of 174 prosthetic joint infections (19%) were polymicrobial. The 2-year cumulative probability of success of treating polymicrobial and monomicrobial PJIs was 63.8% and 72.8%, respectively. Twenty-six percent, 38%, and 29% of PJIs were treated with two-stage exchange, débridement and retention, or resection arthroplasty, respectively, and the 2-year survival rate free of treatment failure in each group was 77.7% (95% confidence interval, 42.8%–94.2%), 52.7% (95% confidence interval, 28.4%–75.9%), and 64.2% (95% confidence interval, 28.7%–88.9%). Methicillin-resistant Staphylococcus aureus (26.4% versus 7.1%) and anaerobes (11.7% versus 2.8%) were more common in polymicrobial PJIs. Polymicrobial PJIs occurred in patients with a soft tissue defect/dehiscence (23.5% versus 2.8%), drainage (79.4% versus 39.2%), or prior local irradiation (8.8% versus 0.71%). We found the following factors associated with polymicrobial prosthetic joint infections: the presence of a soft tissue defect/wound dehiscence (odds ratio, 5.9), drainage (odds ratio, 5.0), and age 65 years or older (odds ratio, 2.8).
Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0230-7
PMCID: PMC2384015  PMID: 18421538
5.  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
6.  The Diagnosis of Periprosthetic Infection 
Periprosthetic infection (PJI) is the most serious joint replacement complication, occurring in 0.8-1.9% of knee arthroplasties and 0.3-1.7% of hip arthroplasties. A definition of PJI was proposed in the November 2011 issue of the journal Clinical Orthopedics and Related Research. The presence of a fistula or of local inflammatory signs is indicative of PJI, but in many cases local pain is the only symptom. In the absence of underlying inflammatory conditions, C-reactive protein measurement is the most useful preoperative blood test for detecting infection associated with a prosthetic joint. The most useful preoperative diagnostic test is the aspiration of synovial joint fluid to obtain a total and differential cell count and culture. Intraoperative frozen sections of periprosthetic tissues produce excellent accuracy in predicting a diagnosis of PJI but only moderate accuracy in ruling out the diagnosis. In this process, obtaining a quality sample is the first step, and determines the quality of microbiological results. Specimens for culture should be obtained prior to the initiation of antibiotic treatment. Sonication of a removed implant may increase the culture yield. Plain radiography has low sensitivity and low specificity for detecting infection associated with a prosthetic joint. Computed tomography and magnetic resonance imaging may be useful in the evaluation of complex cases, but metal inserts interfere with these tests, and abnormalities may be non-specific. Labelled-leucocyte imaging (e.g., leucocytes labelled with indium-111) combined with bone marrow imaging with the use of technetium-99m–labelled sulphur colloid is considered the imaging test of choice when imaging is necessary.
doi:10.2174/1874325001307010178
PMCID: PMC3722546  PMID: 23898349
Diagnosis; periprosthetic infection; joint replacement; hip; knee.
7.  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
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.  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
10.  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
11.  Culture-negative Periprosthetic Joint Infection Does Not Preclude Infection Control 
Background
Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty. Lack of confirmation of an infecting organism poses a challenge with regard to the selection of an appropriate antibiotic agent and surgical treatment. It is unclear whether patients with negative cultures presumed to have infections achieve similar rates of infection-free survival as those with positive cultures.
Questions/purposes
The purposes of this study were (1) to report the infection control rates using irrigation and débridement and two-stage exchange for treatment of culture-negative PJIs; and (2) to compare infection control rates in culture-negative cases with those in culture-positive cases.
Methods
We retrospectively reviewed 55 patients with culture-negative PJI treated between 2000 and 2007. We compared the infection-free survival rate in the culture-negative patients with that of 295 culture-positive cases of PJI.
Results
Overall infection control rate in culture-negative cases was 73% at minimum 1-year followup (mean, 47 months; range, 12–119 months). We found similar infection control rates in culture-negative and culture-positive PJI. Infection-free survival rates in both groups were highest after two-stage exchange arthroplasty and postoperative vancomycin therapy.
Conclusion
Our observations suggest aggressive two-stage exchange arthroplasty and postoperative parenteral vancomycin therapy in patients with culture-negative PJI achieves similar rates of infection-free survival as with patients having culture-positive PJI.
Level of Evidence
Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2434-0
PMCID: PMC3441976  PMID: 22733184
12.  Operating Room Traffic is a Major Concern During Total Joint Arthroplasty 
Background
Periprosthetic joint infection (PJI) is a challenging complication associated with total joint arthroplasty (TJA). Traffic in the operating room (OR) increases bacterial counts in the OR, and may lead to increased rates of infection.
Question/purposes
Our purposes were to (1) define the incidence of door opening during primary and revision TJA, providing a comparison between the two types of procedures, and (2) identify the causes of door opening in order to develop a strategy to reduce traffic in the operating room.
Methods
An observer collected data during 80 primary and 36 revision TJAs. Surgeries were performed under vertical, laminar flow. Operating room personnel were unaware of the observer, thus removing bias from traffic. The observer documented the number, reason, and personnel involved in the event of a door opening from time of tray opening to closure of the surgical site.
Results
The average operating time for primary and revision procedures was 92 and 161 minutes, respectively. Average door openings were 60 in primary cases and 135 in revisions, yielding per minute rates of 0.65 and 0.84, respectively. The circulating nurse and surgical implant representatives constituted the majority of OR traffic.
Conclusions
Traffic in the OR is a major concern during TJA. Revision cases demonstrated a particularly high rate of traffic. Implementation of strategies, such as storage of instruments and components in the operating room and education of OR personnel, is required to reduce door openings in the OR.
doi:10.1007/s11999-012-2252-4
PMCID: PMC3441983  PMID: 22302655
13.  Prosthetic Joint Infection Diagnosis Using Broad-Range PCR of Biofilms Dislodged from Knee and Hip Arthroplasty Surfaces Using Sonication 
Journal of Clinical Microbiology  2012;50(11):3501-3508.
Periprosthetic tissue and/or synovial fluid PCR has been previously studied for prosthetic joint infection (PJI) diagnosis; however, few studies have assessed the utility of PCR on biofilms dislodged from the surface of explanted arthroplasties using vortexing and sonication (i.e., sonicate fluid PCR). We compared sonicate fluid 16S rRNA gene real-time PCR and sequencing to culture of synovial fluid, tissue, and sonicate fluid for the microbiologic diagnosis of PJI. PCR sequences generating mixed chromatograms were decatenated using RipSeq Mixed. We studied sonicate fluids from 135 and 231 subjects with PJI and aseptic failure, respectively. Synovial fluid, tissue, and sonicate fluid culture and sonicate fluid PCR had similar sensitivities (64.7, 70.4, 72.6, and 70.4%, respectively; P > 0.05) and specificities (96.9, 98.7, 98.3, and 97.8%, respectively; P > 0.05). Combining sonicate fluid culture and PCR, the sensitivity was higher (78.5%, P < 0.05) than those of individual tests, with similar specificity (97.0%). Thirteen subjects had positive sonicate fluid culture but negative PCR, and 11 had negative sonicate fluid culture but positive PCR (among which 7 had prior use of antimicrobials). Broad-range PCR and culture of sonicate fluid have equivalent performance for PJI diagnosis.
doi:10.1128/JCM.00834-12
PMCID: PMC3486250  PMID: 22895042
14.  Rapid Molecular Microbiologic Diagnosis of Prosthetic Joint Infection 
Journal of Clinical Microbiology  2013;51(7):2280-2287.
We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.
doi:10.1128/JCM.00335-13
PMCID: PMC3697690  PMID: 23658273
15.  Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection 
International Orthopaedics  2010;35(5):647-654.
During a two-stage revision for prosthetic joint infections (PJI), joint aspirations, open tissue sampling and serum inflammatory markers are performed before re-implantation to exclude ongoing silent infection. We investigated the performance of these diagnostic procedures on the risk of recurrence of PJI among asymptomatic patients undergoing a two-stage revision. A total of 62 PJI were found in 58 patients. All patients had intra-operative surgical exploration during re-implantation, and 48 of them had intra-operative microbiological swabs. Additionally, 18 joint aspirations and one open biopsy were performed before second-stage reimplantation. Recurrence or persistence of PJI occurred in 12 cases with a mean delay of 218 days after re-implantation, but only four pre- or intraoperative invasive joint samples had grown a pathogen in cultures. In at least seven recurrent PJIs (58%), patients had a normal C-reactive protein (CRP, <10 mg/l) level before re-implantation. The sensitivity, specificity, positive predictive and negative predictive values of pre-operative invasive joint aspiration and CRP for the prediction of PJI recurrence was 0.58, 0.88, 0.5, 0.84 and 0.17, 0.81, 0.13, 0.86, respectively. As a conclusion, pre-operative joint aspiration, intraoperative bacterial sampling, surgical exploration and serum inflammatory markers are poor predictors of PJI recurrence. The onset of reinfection usually occurs far later than reimplantation.
doi:10.1007/s00264-010-1014-8
PMCID: PMC3080509  PMID: 20419507
16.  One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome 
Objectives
We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR).
Methods
We retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used.
Results
One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics [hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4–12.8, P = 0.01]. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5–33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome.
Conclusions
PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure.
doi:10.1093/jac/dkp107
PMCID: PMC2680346  PMID: 19336454
prosthetic; infection; management
17.  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
18.  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
19.  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
20.  Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis▿  
Antimicrobial Agents and Chemotherapy  2009;53(11):4772-4777.
The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone.
doi:10.1128/AAC.00188-09
PMCID: PMC2772308  PMID: 19687237
21.  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
22.  Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty 
Antimicrobial Agents and Chemotherapy  2012;56(11):5626-5632.
The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.
doi:10.1128/AAC.00038-12
PMCID: PMC3486533  PMID: 22908174
23.  Periprosthetic Joint Infections 
Implantation of joint prostheses is becoming increasingly common, especially for the hip and knee. Infection is considered to be the most devastating of prosthesis-related complications, leading to prolonged hospitalization, repeated surgical intervention, and even definitive loss of the implant. The main risk factors to periprosthetic joint infections (PJIs) are advanced age, malnutrition, obesity, diabetes mellitus, HIV infection at an advanced stage, presence of distant infectious foci, and antecedents of arthroscopy or infection in previous arthroplasty. Joint prostheses can become infected through three different routes: direct implantation, hematogenic infection, and reactivation of latent infection. Gram-positive bacteria predominate in cases of PJI, mainly Staphylococcus aureus and Staphylococcus epidermidis. PJIs present characteristic signs that can be divided into acute and chronic manifestations. The main imaging method used in diagnosing joint prosthesis infections is X-ray. Computed tomography (CT) scan may assist in distinguishing between septic and aseptic loosening. Three-phase bone scintigraphy using technetium has high sensitivity, but low specificity. Positron emission tomography using fluorodeoxyglucose (FDG-PET) presents very divergent results in the literature. Definitive diagnosis of infection should be made by isolating the microorganism through cultures on material obtained from joint fluid puncturing, surgical wound secretions, surgical debridement procedures, or sonication fluid. Success in treating PJI depends on extensive surgical debridement and adequate and effective antibiotic therapy. Treatment in two stages using a spacer is recommended for most chronic infections in arthroplasty cases. Treatment in a single procedure is appropriate in carefully selected cases.
doi:10.1155/2013/542796
PMCID: PMC3760112  PMID: 24023542
24.  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
25.  Estimating Risk in Medicare Patients With THA: An Electronic Risk Calculator for Periprosthetic Joint Infection and Mortality 
Background
Although risk factors for periprosthetic joint infection (PJI) and mortality after total hip arthroplasty (THA) have been identified, interactions between specific patient risk factors are poorly understood. Therefore, it is difficult for surgeons to counsel patients on their individual risk of PJI or mortality after THA.
Questions/purposes
We evaluated the interaction between patient clinical and demographic factors on the risk of PJI and mortality after THA and developed an electronic risk calculator for estimating the patient-specific risk of PJI and mortality in Medicare patients with THA.
Methods
We used the Medicare 5% sample claims database to calculate the risk of PJI within 2 years and mortality within 90 days after THA in 53,252 Medicare patients with primary THAs between 1998 and 2009. Logistic regression using 29 comorbid conditions, age, sex, race, and socioeconomic status were used as inputs to develop an electronic risk calculator to estimate patient-specific risk of PJI and mortality after THA.
Results
The overall 2-year risk of PJI and 90-day risk of mortality after primary THA were 2.07% and 1.30%, respectively. White women aged 70 to 74 years with alcohol abuse, depression, electrolyte disorder, peptic ulcer disease, urinary tract infection, rheumatologic disease, preoperative anemia, cardiopulmonary (cardiac arrhythmia, congestive heart failure, ischemic heart disease, chronic pulmonary disease) comorbidities, and peripheral vascular disease were at highest risk for PJI. White women aged 65 to 69 years with electrolyte disorder, hemiplegia/paraplegia, hypertension, hypothyroidism, metastatic tumor, preoperative anemia, coagulopathy, cardiopulmonary (congestive heart failure, chronic pulmonary disease) and psychiatric (psychoses, depression) comorbidities, malignancies, and peripheral vascular disease were at highest risk for mortality. An electronic risk calculator was developed to estimate the risk of PJI and mortality in Medicare patients with THA.
Conclusions
This electronic risk calculator can be used to counsel Medicare patients regarding their patient-specific risks of PJI and mortality after THA.
Level of Evidence
Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2605-z
PMCID: PMC3549162  PMID: 23179112

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