Tad M. Mabry

Inflammatory blood laboratory levels as markers of prosthetic joint infection: A systematic review and meta-analysis

BACKGROUND The preoperative diagnosis of prosthetic joint infection in patients with a total hip or knee arthroplasty may rely in part on the use of systemic inflammation markers. These markers have unclear accuracy. The objective of this review was to summarize the evidence on the accuracy of the peripheral white blood-cell count, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum interleukin-6 levels for the diagnosis of prosthetic joint infection. METHODS We searched electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus) from 1950 through 2009. Eligible studies evaluated the accuracy of white blood-cell count, erythrocyte sedimentation rate, serum C-reactive protein level, and serum interleukin-6 level for the intraoperative diagnosis of prosthetic joint infection at the time of revision arthroplasty. Two reviewers working independently extracted study characteristics and data to estimate the diagnostic odds ratio and 95% confidence interval for each result. RESULTS We included thirty eligible studies that included 3909 revision total hip or knee arthroplasties. The prevalence of prosthetic joint infection was 32.5% (1270 of 3909). The accuracy of assessed inflammation markers, represented with a diagnostic odds ratio, was 314.7 (95% confidence interval, 113.0 to 876.8) for interleukin-6 (three studies), 13.1 (95% confidence interval, 7.9 to 21.7) for C-reactive protein level (twenty-three studies), 7.2 (95% confidence interval, 4.7 to 10.9) for erythrocyte sedimentation rate (twenty-five studies), and 4.4 (95% confidence interval, 2.9 to 6.6) for white blood-cell count (fifteen studies). CONCLUSIONS The diagnostic accuracy for prosthetic joint infection was best for interleukin-6, followed by C-reactive protein level, erythrocyte sedimentation rate, and white blood-cell count. Given the limited numbers of studies assessing interleukin-6 levels, further investigations assessing the accuracy of interleukin-6 for the diagnosis of prosthetic joint infection are warranted.

Utility of intraoperative frozen section histopathology in the diagnosis of periprosthetic joint infection: A systematic review and meta-analysis

BACKGROUND The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown. METHODS We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010. RESULTS Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined. CONCLUSIONS Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culture-positive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per high-power field.

The Mayo prosthetic joint infection risk score: implication for surgical site infection reporting and risk stratification.

OBJECTIVE The goal of this study was to develop a prognostic scoring system for the development of prosthetic joint infection (PJI) that could risk-stratify patients undergoing total hip (THA) or total knee (TKA) arthroplasties. DESIGN Previously reported case-control study. SETTING Tertiary referral care setting from 2001 through 2006. METHODS A derivation data set of 339 cases and 339 controls was used to develop 2 scores. A baseline score and a 1-month-postsurgery risk score were computed as a function of the relative contributions of risk factors for each model. Points were assigned for the presence of each factor and then summed to get a subjects risk score. RESULTS The following risk factors were detected from multivariable modeling and incorporated into the baseline Mayo PJI risk score: body mass index, prior other operation on the index joint, prior arthroplasty, immunosuppression, ASA score, and procedure duration (c index, 0.722). The 1-month-postsurgery risk score contained the same variables in addition to postoperative wound drainage (c index, 0.716). CONCLUSION The baseline score might help with risk stratification in relation to public reporting and reimbursement as well as targeted prevention strategies in patients undergoing THA or TKA. The application of the 1-month-postsurgery PJI risk score to patients undergoing THA or TKA might benefit those undergoing workup for PJI.

Utility of Intraoperative Frozen SectionHistopathology in the Diagnosis ofPeriprosthetic Joint Infection

BACKGROUND The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown. METHODS We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010. RESULTS Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined. CONCLUSIONS Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culture-positive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per high-power field.

Comparison of intramedullary nailing and external fixation knee arthrodesis for the infected knee replacement.

We analyzed knee arthrodesis for the infected total knee replacement (TKR) using two different fixation techniques. Patients undergoing knee arthrodesis for infected TKR were identified and rates of successful fusion and recurrence of infection were compared using Cox proportional hazard models. Eighty-five consecutive patients who underwent knee arthrodesis were followed until union, nonunion, amputation, or death. External fixation achieved successful fusion in 41 of 61 patients and was associated with a 4.9% rate of deep infection. Fusion was successful in 23 of 24 patients with intramedullary (IM) nailing and was associated with an 8.3% rate of deep infection. We observed similar fusion and infection rates with the two techniques. Thirty-four patients (40%) had complications. Knee arthrodesis remains a reasonable salvage alternative for the difficult infected TKR. Complication rates are high irrespective of the technique, and one must consider the risks of both nonunion and infection when choosing the fixation method in this setting. IM nailing appears to have a higher rate of successful union but a higher risk of recurrent infection when compared with external fixation knee arthrodesis.Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Morbid obesity: a significant risk factor for failure of two-stage revision total knee arthroplasty for infection.

BACKGROUND Obese patients have a higher risk of complications following primary total knee arthroplasty, including periprosthetic joint infection. However, there is a paucity of data concerning the efficacy of two-stage revision arthroplasty in obese patients. METHODS We performed a two-to-one matched cohort study to compare the outcomes of thirty-seven morbidly obese patients (those with a body mass index of ≥ 40 kg/m(2)) who underwent two-stage revision total knee arthroplasty for periprosthetic joint infection following primary total knee arthroplasty with the outcomes of seventy-four non-obese patients (those with a body mass index of <30 kg/m(2)). Groups were matched by sex, age, and date of reimplantation. Outcomes included subsequent revision, reinfection, reoperation, and Knee Society pain and function scores. The minimum follow-up time was five years. RESULTS Morbidly obese patients had a significantly increased risk for revision surgery (32% compared with 11%; p < 0.01), reinfection (22% compared with 4%; p < 0.01), and reoperation (51% compared with 16%; p < 0.01). Implant survival rates were 80% for the morbidly obese group and 97% for the non-obese group at five years and 55% for the morbidly obese group and 82% for the non-obese group at ten years. Knee Society pain scores improved significantly following surgery in both groups; the mean scores (and standard deviation) were 50 ± 5 points for the morbidly obese group and 55 ± 2 points for the non-obese group (p = 0.06) preoperatively, 74 ± 5 points for the morbidly obese group and 89 ± 2 points for the non-obese group (p < 0.0001) at two years, 72 ± 6 points for the morbidly obese group and 88 ± 3 points for the non-obese group (p < 0.0001) at five years, and 56 ± 9 points for the morbidly obese group and 84 ± 3 points for the non-obese group (p = 0.01) at ten years. CONCLUSIONS Morbid obesity significantly increased the risk of subsequent revision, reoperation, and reinfection following two-stage revision total knee arthroplasty for infection. In addition, these patients had worse pain relief and overall function at intermediate-term clinical follow-up. Although two-stage revision should remain a standard treatment for chronic periprosthetic joint infection in morbidly obese patients, increased failure rates and poorer outcomes should be anticipated.

Diabetes Mellitus, Hyperglycemia, Hemoglobin A1C and the Risk of Prosthetic Joint Infections in Total Hip and Knee Arthroplasty

Diabetes mellitus is an established risk factor for infections but evidence is conflicting to what extent perioperative hyperglycemia, glycemic control and treatment around the time of surgery modify the risk of prosthetic joint infections (PJIs). In a cohort of 20,171 total hip and knee arthroplasty procedures, we observed a significantly higher risk of PJIs among patients with a diagnosis of diabetes mellitus (hazard ratio [HR] 1.55, 95% CI 1.11, 2.16), patients using diabetes medications (HR 1.56, 95% CI 1.08, 2.25) and patients with perioperative hyperglycemia (HR 1.59, 95% CI 1.07, 2.35), but the effects were attenuated after adjusting for body mass index, type of surgery, ASA score and operative time. Although data were limited, there was no association between hemoglobin A1c values and PJIs.

Long-term results of total hip arthroplasty for femoral neck fracture nonunion.

BACKGROUND Hip arthroplasty for the treatment of nonunion at the site of a femoral neck fracture has provided good short-term results. The purpose of the present study was to evaluate the long-term results and complications of total hip arthroplasty for the treatment of femoral neck nonunion. METHODS The records of ninety-nine patients who had been managed with total hip arthroplasty with use of a cemented Charnley acetabular component and a cemented Charnley monoblock femoral component for the treatment of a femoral neck nonunion were retrospectively reviewed. The average age at the time of the arthroplasty was sixty-eight years. Eighty-four patients (85%) were followed until death, revision, or component removal or for at least two years (mean, 12.2 years) postoperatively. RESULTS Twelve patients were treated with revision (eleven) or resection arthroplasty (one), eleven were lost to follow-up, and four died less than two years postoperatively. Of the remaining seventy-two unrevised hips that were followed for at least two years, sixty-nine (96%) had no or mild hip pain at the time of the last follow-up. The rate of component survival free of revision or removal for any reason was 93% at ten years and 76% at twenty years. The risk factors that were significantly associated with revision for aseptic loosening included an age of less than sixty-five years at the time of the arthroplasty (p = 0.045), a body-mass index of >/=30 (p < 0.01), and male gender (p = 0.02). The second most common complication after loosening was dislocation, which occurred in nine patients (9%). CONCLUSIONS Total hip arthroplasty is an effective method for the treatment of nonunion of the femoral neck and provides satisfactory long-term results. However, the rate of implant survival is poorer than that reported in most other studies of Charnley total hip arthroplasty in the general population.

Incidence, Secular Trends, and Outcomes of Prosthetic Joint Infection: 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. PARTICIPANTS Residents who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 1, 1969, and December 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 case patients. RESULTS A total of 7,375 THAs or TKAs 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 [Formula: see text] years. The cumulative incidence of PJI was 0.5%, 0.8%, and 1.4% after 1, 5, and 10 years after arthroplasty, respectively. Overall, the rate of survival free of clinical failure after treatment of PJI was 76.8% (95% confidence interval [CI], 64.3-85.2) and 65.2% (95% CI, 33.1-76.2) at 3 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 40 years.

Laboratory and Clinical Characteristics of Staphylococcus lugdunensis Prosthetic Joint Infections

ABSTRACT 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.