The introduction of the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection (PJI) in 2011 resulted in improvements in diagnostic confidence and research ...collaboration. The emergence of new diagnostic tests and the lessons we have learned from the past 7 years using the MSIS definition, prompted us to develop an evidence-based and validated updated version of the criteria.
This multi-institutional study of patients undergoing revision total joint arthroplasty was conducted at 3 academic centers. For the development of the new diagnostic criteria, PJI and aseptic patient cohorts were stringently defined: PJI cases were defined using only major criteria from the MSIS definition (n = 684) and aseptic cases underwent one-stage revision for a noninfective indication and did not fail within 2 years (n = 820). Serum C-reactive protein (CRP), D-dimer, erythrocyte sedimentation rate were investigated, as well as synovial white blood cell count, polymorphonuclear percentage, leukocyte esterase, alpha-defensin, and synovial CRP. Intraoperative findings included frozen section, presence of purulence, and isolation of a pathogen by culture. A stepwise approach using random forest analysis and multivariate regression was used to generate relative weights for each diagnostic marker. Preoperative and intraoperative definitions were created based on beta coefficients. The new definition was then validated on an external cohort of 222 patients with PJI who subsequently failed with reinfection and 200 aseptic patients. The performance of the new criteria was compared to the established MSIS and the prior International Consensus Meeting definitions.
Two positive cultures or the presence of a sinus tract were considered as major criteria and diagnostic of PJI. The calculated weights of an elevated serum CRP (>1 mg/dL), D-dimer (>860 ng/mL), and erythrocyte sedimentation rate (>30 mm/h) were 2, 2, and 1 points, respectively. Furthermore, elevated synovial fluid white blood cell count (>3000 cells/μL), alpha-defensin (signal-to-cutoff ratio >1), leukocyte esterase (++), polymorphonuclear percentage (>80%), and synovial CRP (>6.9 mg/L) received 3, 3, 3, 2, and 1 points, respectively. Patients with an aggregate score of greater than or equal to 6 were considered infected, while a score between 2 and 5 required the inclusion of intraoperative findings for confirming or refuting the diagnosis. Intraoperative findings of positive histology, purulence, and single positive culture were assigned 3, 3, and 2 points, respectively. Combined with the preoperative score, a total of greater than or equal to 6 was considered infected, a score between 4 and 5 was inconclusive, and a score of 3 or less was not infected. The new criteria demonstrated a higher sensitivity of 97.7% compared to the MSIS (79.3%) and International Consensus Meeting definition (86.9%), with a similar specificity of 99.5%.
This study offers an evidence-based definition for diagnosing hip and knee PJI, which has shown excellent performance on formal external validation.
Opioids have well-known immunosuppressive properties and preoperative opioid consumption is relatively common among patients undergoing total joint arthroplasty (TJA). The hypothesis of this study ...was that utilization of opioids preoperatively would increase the incidence of subsequent periprosthetic joint infection (PJI) in patients undergoing primary TJA.
A comparative cohort study design was set up that used a cohort of 23,754 TJA patients at a single institution. Patient records were reviewed to extract relevant information, in particular details of opioid consumption, and an internal institutional database of PJI was cross-referenced against the cohort to identify patients who developed a PJI within 2 years of index arthroplasty. Univariate and multivariate linear regression analyses were used to examine the potential association between preoperative opioid consumption and the development of PJI.
Among the total cohort of 23,754 patients, 5051 (21.3%) patients used opioids before index arthroplasty. Preoperative opioid usage overall was found to be a significant risk factor for development of PJI in the univariate (odds ratio, 1.63; P = .005) and multivariate analyses (adjusted odds ratio, 1.53 95% confidence interval, 1.14-2.05, P = .005).
Preoperative opioid consumption is independently associated with a higher risk of developing a PJI after primary TJA. These findings underscore a need for caution when prescribing opioids in patients with degenerative joint disease who may later require arthroplasty.
Two-stage exchange arthroplasty remains the preferred method to treat periprosthetic joint infection. The aim of this study was to investigate the clinical course of periprosthetic joint infection ...following resection arthroplasty and insertion of a spacer.
Our institutional database was used to identify 504 cases of periprosthetic joint infection (326 knees and 178 hips) treated with resection arthroplasty and spacer insertion as part of a two-stage exchange arthroplasty. A review of the patient charts was performed to extract information relevant to the objectives of this study that included the details of the clinical course following resection arthroplasty.
The mean follow-up duration after initial spacer implantation was 56.2 months. Reimplantation occurred in the joints of 417 (82.7%) of 504 cases. Of these 417 cases, 329 (78.9%) had a minimum one-year follow-up, and 81.4% of these had successful treatment. The mean duration from resection arthroplasty to reimplantation was 4.2 months (range, 0.7 to 131.7 months). Sixty (11.9%) of the 504 joints required interim spacer exchange(s). Of the eighty-seven cases that did not undergo reimplantation, six (6.9%) required amputation, five (5.7%) underwent a Girdlestone procedure, four (4.6%) underwent arthrodesis, and seventy-two (82.8%) underwent spacer retention. Thirty-six patients died in the interstage period.
The commonly held belief that two-stage exchange arthroplasty carries a high success rate for the eradication of periprosthetic joint infection may need to be reexamined. A considerable number of patients undergoing the first stage of a two-stage procedure do not undergo a subsequent reimplantation for a variety of reasons or require an additional spacer exchange in the interim. Reports on the success of two-stage exchange should account for the mortality of these patients and for patients who never undergo reimplantation.
The treatment outcomes of periprosthetic joint infection are frequently dependent on characteristics of the causative organism. The objective of this comparative study was to investigate the ...prevalence of and risk factors for development of polymicrobial periprosthetic joint infection, and the outcome of surgical treatment of these patients.
All patients with polymicrobial, monomicrobial, or culture-negative periprosthetic joint infection treated from 2000 to 2014 were identified at a single institution. Ninety-five patients with a polymicrobial periprosthetic joint infection had a minimum follow-up of 12 months. We matched patients with a polymicrobial periprosthetic joint infection with the other cohorts using propensity score matching for several important parameters. Treatment success was defined according to the Delphi criteria; Kaplan-Meier survivorship curves were generated to demonstrate this. A multiple logistic regression analysis was performed to determine risk factors for a polymicrobial periprosthetic joint infection.
Overall, 10.3% (108 of 1,045) of the periprosthetic joint infections treated at our institution were polymicrobial in nature. Patients with a polymicrobial periprosthetic joint infection had a higher failure rate at 50.5% (48 of 95) compared with the monomicrobial periprosthetic joint infection cohort at 31.5% (63 of 200) and the culture-negative periprosthetic joint infection cohort at 30.2% (48 of 159) (p = 0.003). The survivorship of the polymicrobial periprosthetic joint infection group was 52.2% at the 2-year follow-up, 49.3% at the 5-year follow-up, and 46.8% at the 10-year follow-up. Patients with polymicrobial periprosthetic joint infection had a higher rate of amputation (odds ratio OR, 3.80 95% confidence interval (CI), 1.34 to 10.80), arthrodesis (OR, 11.06 95% CI, 1.27 to 96.00), and periprosthetic joint infection-related mortality (OR, 7.88 95% CI, 1.60 to 38.67) compared with patients with monomicrobial periprosthetic joint infection. Isolation of gram-negative organisms (p < 0.01), enterococci (p < 0.01), Escherichia coli (p < 0.01), and atypical organisms (p < 0.01) was associated with polymicrobial periprosthetic joint infection. Only the presence of a sinus tract (OR, 2.20 95% CI, 1.39 to 3.47; p = 0.001) was a significant risk factor for polymicrobial periprosthetic joint infection on multivariate analysis.
This study reveals that polymicrobial periprosthetic joint infection, occurring at a relatively low rate, is associated with poor outcomes when compared with monomicrobial and culture-negative periprosthetic joint infection. Patients with polymicrobial infections were more likely to require a salvage procedure or to have periprosthetic joint infection-related mortality. Polymicrobial periprosthetic joint infection was associated with soft-tissue defects such as a sinus tract and certain types of organisms, which should be considered when administering antibiotics to these patients.
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects ...fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.
This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for aseptic failure (n = 86), revision for PJI (n = 57), or reimplantation (n = 29) or who had infection in a site other than a joint (n = 50). PJI was defined using the Musculoskeletal Infection Society criteria. In all patients, serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were measured preoperatively.
The median D-dimer level was significantly higher (p < 0.0001) for the patients with PJI (1,110 ng/mL range, 243 to 8,487 ng/mL) than for the patients with aseptic failure (299 ng/mL range, 106 to 2,571 ng/mL). Using the Youden index, 850 ng/mL was determined as the optimal threshold value for serum D-dimer for the diagnosis of PJI. Serum D-dimer outperformed both ESR and serum CRP, with a sensitivity of 89% and a specificity of 93%. ESR and CRP had a sensitivity of 73% and 79% and a specificity of 78% and 80%, respectively. The sensitivity and specificity of ESR and CRP combined was 84% (95% confidence interval CI, 76% to 90%) and 47% (95% CI, 36% to 58%), respectively.
It appears that serum D-dimer is a promising marker for the diagnosis of PJI. This test may also have a great utility for determining the optimal timing of reimplantation.
Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Background
In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant
...Staphylococcus aureus
(MRSA). Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered.
Questions/purposes
(1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury?
Methods
A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During the same period, 5810 patients underwent primary TJA and received cefazolin monotherapy. A chart review was performed to obtain patient characteristics, antibiotic dose and timing of administration, and microbiology data. Adequate vancomycin dosing was defined as 15 mg/kg and within the 125-mg range. Vancomycin levels were calculated at the beginning and end of surgery using pharmacokinetic equations. Levels of 15 mg/L were considered adequate. Logistic regression, chi square tests, and analysis of variance were performed.
Results
Among primary TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 2%) compared with patients receiving cefazolin prophylaxis (62 of 5810 1%; adjusted odds ratio, 1.587 1.004–2.508; p = 0.048). Ten percent of PJIs in the vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was adequately dosed according to weight-based dosage recommendations. Furthermore, 94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom 64% (1105 of 1726) were underdosed. All patients had vancomycin infusion initiated within 2 hours before incision. A weight-based protocol would have resulted in fewer patients having unacceptably low vancomycin levels (< 15 mg/L) compared with those with actual fixed dosing, both for the beginning of surgery at the time of incision (zero of 1828 0% versus 471 of 1828 26%; odds ratio, 0.001 0.000–0.013; p < 0.001) and at the end of surgery (33 of 1828 2% versus 746 of 1828 41%; odds ratio, 0.027 0.019–0.038; p < 0.001). Between the vancomycin dosage groups, there were no differences in the rate of nephrotoxicity (underdosed: 12 of 1130 1%, adequately dosed: five of 518 1%, overdosed: four of 180 2%, p = 0.363) and acute kidney injury (underdosed: 28 of 1130 2%, adequately dosed: 10 of 518 2%, overdosed: six of 180 3%, p = 0.561).
Conclusions
The majority of patients given vancomycin prophylaxis are underdosed according to the weight-based dosage recommendations, and MRSA did not occur in patients who were adequately dosed with vancomycin. Surgeons should thus ensure that their patients are adequately dosed with vancomycin using the recommendation of 15 mg/kg and that the dose of vancomycin is administered in a timely fashion. Furthermore, and based on the findings of this study, we have moved toward limiting the utilization of vancomycin prophylaxis for patients undergoing elective arthroplasty at our institution.
Level of Evidence
Level III, therapeutic study.
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