White Blood Cell Count Is the Most Reliable Test for the Diagnosis of Septic Arthritis After Anterior Cruciate Ligament Reconstruction: An Observational Study of 38 Patients.

PURPOSE: (1) To evaluate the diagnostic testing performance of the synovial white blood cell (WBC) count, polymorphonuclear cell percentage, and synovial glucose, synovial protein, synovial lactate dehydrogenase, and synovial C-reactive protein levels as diagnostic markers for the diagnosis of septic arthritis after anterior cruciate ligament (ACL) reconstruction; (2) to define the ideal thresholds of the aforementioned tests, leading to the optimal sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy; and (3) to define the sensitivity of synovial fluid culture and synovial tissue sample culture, as well as determine whether previous antibiotic treatment may affect the accuracy of these tests. METHODS: We performed a retrospective analysis of all patients readmitted from January 2009 to September 2019 with signs suggestive of septic arthritis and undergoing a knee aspiration for synovial fluid analysis and culture. The receiver operating characteristic curve and the associated area under the curve were constructed for the aforementioned synovial markers. Sensitivity, specificity, PPV, NPV, and accuracy were calculated for the obtained optimal values. Sensitivity was also calculated for synovial fluid culture and synovial tissue sample culture, and the influence of previous antibiotic treatments on culture sensitivity was evaluated. RESULTS: Among 3,408 cases of ACL reconstruction, after the exclusion of 13 patients not meeting the inclusion criteria, 24 infected and 14 uninfected patients were reviewed and included in the analysis. The diagnosis was confirmed by the presence of 2 positive culture findings with the same isolated microorganism or at least 3 of the 4 following criteria: elevated serum C-reactive protein level and erythrocyte sedimentation rate, positive results of histologic analysis of synovial tissue, macroscopic evidence of purulence, and 1 positive culture finding. The receiver operating characteristic curve analysis showed that the most reliable marker for the diagnosis of septic arthritis after ACL reconstruction was the synovial WBC count (area under the curve, 0.89). A cutoff value of 28,100 cells/mL presented the highest accuracy (0.85), highest PPV (0.94), and highest NPV (0.76); moreover, with the threshold set at 40,000 cells/mL, postoperative infection could be diagnosed with 100% specificity. The sensitivity of synovial fluid culture was significantly lower than the sensitivity of synovial tissue sample culture (0.63 vs 0.96, P = .0045); moreover, the sensitivity further decreased if patients took antibiotics before aspiration (0.44 vs 0.73), although this decrease was not statistically significant. CONCLUSIONS: The synovial WBC count is the most reliable test for the diagnosis of septic arthritis after ACL reconstruction. Although the sensitivity of synovial fluid culture is affected by previous antibiotic treatment, the synovial WBC count is not influenced and proves to be useful in the diagnosis of this uncommon complication. LEVEL OF EVIDENCE: Level II, diagnostic study.

Serum CA72-4 is specifically elevated in gout patients and predicts flares.

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.

Is Procalcitonin (PCT) a reliable biomarker for preoperative diagnosing of low grade periprosthetic joint infection? A prospective study.

BACKGROUND: Since a "gold-standard" is missing, diagnosing periprosthetic joint infection (PJI) remains a challenge in orthopedic surgery. The purpose of this study was to evaluate the accuracy of serum and synovial fluid Procalcitonin (S-PCT and SF-PCT) as a diagnostic parameter and to compare it to the biomarkers recommended in the 2018 Definition of periprosthetic hip and knee infection. METHODS: Between August 2018 and July 2019, a prospective cohort study was conducted in 70 patients with painful hip, shoulder and knee arthroplasty. Besides medical history, clinical and laboratory data was gathered. PJI was diagnosed based on the 2018 Definition of periprosthetic hip and knee infection. Preoperative blood and synovial joint fluid were taken for PCT measurement. S-PCT and SF-PCT levels were measured using standard quantitative PCT enzyme immunoassays. RESULTS: Twenty three patients (33%) were classified as the PJI group and fourty seven patient (67%) as the aseptic group. The mean levels of S-PCT were significantly (p <  0.001) higher in the PJI group than those in the aseptic group (PJI 0.05 ± 0.21 ng/mL (0.0-1.03) vs. aseptic 0.02 ± 0.03 ng/mL (0.0-0.18)). In synovial fluid, the mean PCT values in the aseptic group were significantly higher (p <  0.001) than those of PJI group (PJI 2.7 ± 1.4 ng/mL (0.53-9.7) vs. aseptic 8.7 ± 2.5 ng/mL (0.25-87.9)). S- PCT, with a cut-off level of 0.5 ng/mL, had a sensitivity of 13.0% and a specificity of 91.0%. SF-PCT, with a cut-off level of 5.0 ng/mL, had a sensitivity of 13.0% and a specificity of 52.0%. CONCLUSION: S-PCT and SF-PCT appeared to be no reliable biomarkers in the differential diagnosis of PJI from aseptic loosening in total joint arthroplasty.

C-reactive protein is not a screening tool for late periprosthetic joint infection.

BACKGROUND: Preoperative diagnosis of periprosthetic joint infection (PJI) is important because of the therapeutic consequences. The aim of the present study is to investigate whether the serum C-reactive protein (CRP) level can be used as a screening tool for late PJI. MATERIALS AND METHODS: A cohort of 390 patients with revision surgery of total hip prostheses (200) or total knee prostheses (190) was assessed for late PJI by determining CRP serum level and performing preoperative aspiration with cultivation and intraoperative tissue analyses with cultivation and histologic examination, using the Musculoskeletal Infection Society (MSIS) and International Consensus Meeting (ICM) criteria. RESULTS: A total of 180 joints were rated as PJI (prevalence 46%). Of these, 42.8% (77) showed a CRP level below 10 mg/L and 28.3% (51) showed a normal CRP level of less than 5 mg/L. The 76.9% of the cases with slow-growing bacteria showed a CRP level below 10 mg/L, and 61.5% showed a normal CRP level. CONCLUSIONS: Serum CRP level should not be used as a screening tool to rule out late PJI. LEVEL OF EVIDENCE: Level 2 (diagnostic study).

Outcomes and predictors of treatment failure following two-stage total joint arthroplasty with articulating spacers for evolutive septic arthritis.

BACKGROUND: The treatment strategy for evolutive septic arthritis (SA) with coexistent degenerative joint disease is not well established. The purposes of this study were to 1) investigate treatment outcome and potential risk factors of treatment failure in patients with evolutive SA following two-stage procedure, including insertion of an antibiotic-loaded spacer at the first stage and subsequent implantation of a new prosthesis; and 2) determine the performance of serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Interleukin-6 (IL-6) in predicting persisting infection at second-stage procedure. METHODS: We retrospectively reviewed 74 patients with evolutive SA of hips and knees who underwent a two-stage TJA between 2008 and 2015. The treatment success was defined according to the modified Delphi criteria and Kaplan-Meier survivorship curves were constructed to determine treatment success. A Cox regression model was performed to identify risk factors for treatment failure. Receiver operating characteristic (ROC) curves were generated to determine the prognostic value of ESR, CRP, and IL-6 in predicting persistent infection before second-stage prostheses implantation. RESULTS: Overall, the treatment success rate was 93% for hips and 100% for knees after the first-stage surgery. The treatment success rate was 89% for hips and 84% for knees after second-stage prosthesis implantation with a mean follow-up of 4.7 (range, 2.2 to 10.8) years. Older age (Hazard ratio [HR] [per 10-year increase], 1.20; 95% confidential interval [CI], 1.11 to 1.62), higher preoperative CRP level (HR [per 1-mg/dL increase], 1.15; 95% CI, 1.04 to 1.28) and resistant organism (HR, 13.96; 95% CI, 3.29 to 19.20) were associated with an increased risk of treatment failure. All serologic tests presented limited values in predicting persisting infection, with the area under ROC curve of ESR, CRP, IL-6 and combination of the three markers was 57.8, 61.6, 60.3, and 62.1%, respectively. CONCLUSIONS: Two-stage TJA is an adequate management of infection control in patients with evolutive SA. The three potential risk factors (old age, high preoperative CRP, and resistant organism profile) may predict treatment failure following a two-stage procedure for evolutive SA. Additionally, serum ESR, CRP, and IL-6 had no benefit in predicting persisting infection before second-stage prostheses implantation. These findings may be useful when treating patients with evolutive SA.

Dorsal subscapularis approach for the surgical drainage of subscapularis intramuscular abscess: a case report.

BACKGROUND: Abscess formation in the subscapularis muscle is a rare clinical condition. Few reports are available regarding the treatment methods and surgical approaches for subscapularis intramuscular abscesses. Here, we describe a case of subscapularis intramuscular abscess that was treated successfully via surgical drainage using a new approach, the "dorsal subscapularis approach". CASE PRESENTATION: A 67-year-old woman presented to our hospital with complaints of fever and disturbance of consciousness. Two days prior to visiting our hospital, right shoulder pain and limited range of motion in the shoulder were noted. Cerebrospinal fluid examination and contrast-enhanced computed tomography (CT) imaging on admission revealed a right subscapularis intramuscular abscess with concomitant bacterial meningitis. The patient's clinical symptoms improved after antibiotic administration for 3 weeks, but the right shoulder pain persisted. Contrast-enhanced CT imaging performed after antibiotic administration revealed an abscess in the right shoulder joint space, in addition to a capsule of the abscess in the right subscapularis muscle. We performed open surgical drainage for the abscess, which had spread from the subscapularis muscle to the glenohumeral joint. Using the deltoid-pectoral approach, we detected exudate and infected granulation tissue in the joint cavity. Furthermore, we separated the dorsal side of the subscapularis muscle from the scapula using a raspatory and detected infected granulation tissue in the subscapularis muscle belly. We performed curettage and washed as much as possible. After surgery, antibiotic administration continued for 2 weeks. The patient's right shoulder pain subsided and CT performed 2 months after surgery revealed no recurrence of infection. CONCLUSIONS: The present case indicated that a subscapularis intramuscular abscess could lead to severe concomitant infections of other organs via the hematogenous route. Thus, early detection and treatment are necessary. Moreover, in this case, surgical drainage using a dorsal subscapularis approach was beneficial to treating the abscess, which had spread from the subscapularis muscle to the glenohumeral joint.

Treatment of acute shoulder infection: can osseous lesion be a rudder in guideline for determining the method of débridement?

BACKGROUND: There is no standard to determine the most appropriate method of operation for the treatment of acute septic arthritis of the shoulder joint. METHODS: We retrospectively reviewed 57 patients who underwent arthroscopic or open débridement for acute shoulder infection between 2001 and 2015. Arthroscopic débridement was performed in 27 patients, and open débridement in 30 patients. According to the presence of bone erosion and/or marginal erosion of cartilage of the humeral head on plain radiographs and magnetic resonance imaging (MRI) images, the cases were classified into 3 groups (group 1, n = 23, without erosions in x-ray and MRI; group 2, n = 21, erosions seen in MRI but not in x-ray; and group 3, n = 13, with erosions seen in both x-ray and MRI). RESULTS: The arthroscopic group had a reinfection rate of 55.6% (15/27), and the open group had a reinfection rate of 16.7% (5/30). The reinfection rates in the arthroscopic and the open groups were 10% (1/10) and 15.4% (2/13) in group 1; 75% (9/12) and 11.1% (1/9) in group 2; and 100% (5/5) and 25% (2/8) in group 3, respectively. At the last follow-up, the mean University of California at Los Angeles score and the average time until normalization of white blood cell, erythrocyte sedimentation rate, and C-reactive protein in the open group showed superior results in the open group (all P < .05). CONCLUSIONS: When preoperative MRI showed bone and/or cartilage erosion of humeral head, the reinfection rate after arthroscopic débridement was above 75%. Therefore, if preoperative MRI showed erosions, open débridement is more likely to be appropriate than arthroscopic débridement.

Plasma Viscosity Has a Role in the Diagnosis of Prosthetic Joint Infection After Total Knee Arthroplasty.

BACKGROUND: The diagnosis of prosthetic joint infection (PJI) is challenging because no single test has consistently demonstrated an adequate discriminative potential. The combination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with adequate thresholds is well established. This study sought to investigate the role of plasma viscosity (PV) in the diagnosis of PJI following painful total knee arthroplasty. METHODS: The medical notes, and hematological and microbiology results of 310 patients who underwent revision for a painful total knee arthroplasty were evaluated. Infection was confirmed using Musculoskeletal Infection Society criteria in 102 patients (32.9%), whereas 208 patients (67.1%) were classified as noninfected. Serum investigations including ESR, CRP, and PV were analyzed using receiver observer curves and optimal cutoff points identified. RESULTS: There was a strong correlation between PV and both ESR and CRP. The area under curve was 0.814 for PV and 0.812 for ESR. Statistical analysis showed noninferiority of PV as compared to ESR in diagnosing PJI. A PV value of ≥ 1.81 mPa.s. had the best efficiency of 82.1%. Combining a CRP ≥ 13.5 mg/L with a PV ≥ 1.81 mPa.s. in a serial test approach yielded the highest specificity of 97.9% and positive likelihood ratio of 22.8. Sensitivity was 47.9% and a negative likelihood ratio of 0.53. CONCLUSION: PV is noninferior to ESR in diagnosing PJI. Its use is justified in clinical practice. It is cheaper, quicker, more efficient, and not influenced by hematocrit levels or medication. In this cohort, a PV value ≥ 1.81 mPa.s. would be an adequate cutoff to diagnose PJI in combination with CRP ≥ 13.5 mg/L.

C-Reactive Protein Predicts Risk of Venous Thromboembolism in Pediatric Musculoskeletal Infection.

BACKGROUND: The rate of venous thromboembolism in children with musculoskeletal infections (MSKIs) is markedly elevated compared with hospitalized children in general. Predictive biomarkers to identify high-risk patients are needed to prevent the significant morbidity and rare mortality associated with thrombotic complications. We hypothesize that overactivation of the acute phase response is associated with the development of pathologic thrombi and we aim to determine whether elevations in C-reactive protein (CRP) are associated with increased rates of thrombosis in pediatric patients with MSKI. METHODS: A retrospective cohort study measuring CRP in pediatric MSKI patients with or without thrombotic complications. RESULTS: The magnitude and duration of elevation in CRP values correlated with the severity of infection and the development of pathologic thrombosis. In multivariable logistic regression, every 20 mg/L increase in peak CRP was associated with a 29% increased risk of thrombosis (P<0.001). Peak and total CRP were strong predictors of thrombosis with area under the receiver-operator curves of 0.90 and 0.92, respectively. CONCLUSIONS: Future prospective studies are warranted to further define the discriminatory power of CRP in predicting infection-provoked thrombosis. Pharmacologic prophylaxis and increased surveillance should be strongly considered in patients with MSKI, particularly those with disseminated disease and marked elevation of CRP. LEVEL OF EVIDENCE: Level III.

Pediatric Septic Arthritis of the Knee: Predictors of Septic Hip Do Not Apply.

BACKGROUND: The early diagnosis of pediatric septic arthritis is paramount to the prevention of long-term sequela. The purpose of this study is to investigate if the commonly used criteria developed by Kocher and colleagues for hip septic arthritis can be used for screening children with suspected septic knee. METHODS: We retrospectively reviewed the charts of patients under the age of 19, between June 2002 to June 2017, who presented to a major tertiary-care children's hospital with septic knee. Diagnostic criteria included either a positive synovial culture from the knee, synovial white blood cell (WBC)>50,000 cells/mm, or synovial WBC count >25,000 cells/mm and clinical agreement of diagnosis from Infectious Disease and Orthopaedic colleagues. Collected data included the initial criteria described by Kocher and colleagues: history of fever, non-weight-bearing, erythrocyte sedimentation rate, and serum WBC as well as a recently modified criterion: C-reactive protein. Univariate analysis was used to determine the quality of these variables in ruling out septic knee. RESULTS: One hundred four patient charts were found to meet our inclusion criteria demonstrating C-reactive protein>20 mg/L (75%), fever (65%), non-weight-bearing status (64%), erythrocyte sedimentation rate>40 mm/h (60%), and WBC>12,000 cells/mm (49%). With the 25 different combinations of these predictors adjusted for, in an escalating manner, 0 predictors suggested a sensitivity of 0.02, 1 predictor a sensitivity of 0.06, 2 predictors a sensitivity of 0.2, 3 predictors a sensitivity of 0.32, 4 predictors a sensitivity of 0.3, and 5 predictors a sensitivity of 0.11. CONCLUSIONS: According to the Kocher criteria of the hip, at 3 or more criteria the probability of septic arthritis becomes 93% with a sensitivity of 0.84 provoking many physicians to use this cutoff in their assessment of hip pain. This study suggests that if these criteria were applied to the knee, 52% of septic knee cases could be missed. There is a need for further investigation of specific criteria of the knee as the markers of the hip septic arthritis are not necessarily applicable in the knee. LEVEL OF EVIDENCE: Level III.

Positive Blood Cultures Decrease the Treatment Success in Acute Hematogenous Periprosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention.

BACKGROUND: The influence of positive blood cultures on surgical outcome of acute hematogenous periprosthetic joint infection (PJI) treated by debridement, antibiotics, and implant retention (DAIR) remains unknown. This study evaluated the influence of positive blood cultures on the treatment success of DAIR in patients with acute hematogenous PJI. METHODS: A retrospective chart review on 49 patients with blood culture data for acute hematogenous PJI was performed from 2005 to 2016 at a single institution. All patients were treated by DAIR and had a minimum follow-up of 1 year. Treatment success was defined by the Delphi criteria. Multivariate logistic regression analysis was performed to identify variables associated with positive blood culture and treatment success. Kaplan-Meier survivorship curves and log-rank tests were used for analysis. RESULTS: Overall, 44.9% (22/49) of blood cultures obtained yielded positive growth. Elevated Elixhauser comorbidity index was a significant risk factor associated with positive blood (adjusted odds ratio [OR], 1.65; 95% confidence interval [CI], 1.13-2.40; P = .049). A positive blood culture was the only significant factor predicting treatment failure in acute hematogenous PJI (OR, 3.94; 95% CI, 1.18-13.1; P = .026) after adjusting for confounding variables. Kaplan-Meier survivorship for infection-free implant survivorship was 53.1% (95% CI, 38.3%-65.8%) at 1 year for all patients, 66.7% (95% CI, 45.7%-81.1%) for patients with negative blood cultures, and 36.4% (95% CI, 17.2%-55.7%) for patients with positive blood cultures (P = .037). CONCLUSION: The presence of positive blood cultures is associated with decreased treatment success of DAIR for acute hematogenous PJI. Patients with more comorbidities may need to be treated more aggressively for a favorable outcome.

Emergence of an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A by capsular switching.

Recently, we have identified an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A isolate from a patient with bacterial meningitis. It belonged to sequence type 8279 (ST8279), a clone identified as XDR serotype 11A isolated in South Korea. We obtained and compared the genome sequences of an XDR 15A and an XDR 11A isolate. The genomes of two XDR isolates were highly identical, except for the capsular polysaccharide (cps) locus and another small region. Capsular switching from 11A to 15A may have occurred via recombination of the cps locus. The emergence of a new XDR clone via capsular switching would be a great concern for public health and in clinical settings.

Validating an Algorithm to Predict Adjacent Musculoskeletal Infections in Pediatric Patients With Septic Arthritis.

BACKGROUND: Septic arthritis is frequently associated with adjacent infections including osteomyelitis and subperiosteal and intramuscular abscesses. While often clinically indiscernible from isolated septic arthritis, the diagnosis of adjacent infections is important in determining the need for additional surgical intervention. MRI has been used as the diagnostic gold standard for assessing adjacent infection. Routine MRI, however, can be resource-intensive and delay surgical treatment. In this context, there is need for additional diagnostic tools to assist clinicians in determining when to obtain preoperative MRI in children with septic arthritis. In a previous investigation by Rosenfeld et al., an algorithm, based on presenting laboratory values and symptoms, was derived to predict adjacent infections in septic arthritis. The clinical applicability of the algorithm was limited, however, in that it was built from and applied on the same population. The current study was done to address this criticism by evaluating the predictive power of the algorithm on a new patient population. QUESTIONS/PURPOSES: (1) Can a previously created algorithm used for predicting adjacent infection in septic arthritis among pediatric patients be validated in a separate population? METHODS: Records for all pediatric patients (1-18 years old) surgically treated for suspected septic arthritis during a 3-year period were retrospectively reviewed (109 patients). Of these patients, only those with a diagnosis of septic arthritis confirmed by synovial fluid analysis were included in the study population. Patients without confirmation of septic arthritis via synovial fluid analysis, Gram stain, or culture were excluded (34 patients). Patients with absence of MRI, younger than 1 year, insufficient laboratory tests, or confounding concurrent illnesses also were excluded (18 patients), resulting in a total of 57 patients in the study population. Five variables which previously were shown to be associated with risk of adjacent infection were collected: patient age (older than 4 years), duration of symptoms (> 3 days), C-reactive protein (> 8.9 mg/L), platelet count (< 310 x 10 cells/µL), and absolute neutrophil count (> 7.2 x 10 cells/µL). Adjacent infections were determined exclusively by preoperative MRI, with all patients in this study undergoing preoperative MRI. MR images were read by pediatric musculoskeletal radiologists and reviewed by the senior author. According to the algorithm we considered the presence of three or more threshold-level variables as a "positive" result, meaning the patient was predicted to have an adjacent infection. Comparing against the gold standard of MRI, the algorithm's accuracy was evaluated in terms of sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: In the new population, the sensitivity and specificity of the algorithm were 86% (95% CI, 0.70-0.95) and 85% (95% CI, 0.64-0.97), respectively. The positive predictive value was determined to be 91% (95% CI, 0.78-0.97), with a negative predictive value of 77% (95% CI, 0.61-0.89). All patients meeting four or more algorithm criteria were found to have septic arthritis with adjacent infection on MRI. CONCLUSIONS: Critical to the clinical applicability of the above-mentioned algorithm was its validation on a separate population different from the one from which it was built. In this study, the algorithm showed reproducible predictive power when tested on a new population. This model potentially can serve as a useful tool to guide patient risk stratification when determining the likelihood of adjacent infection and need of MRI. This better-informed clinical judgement regarding the need for MRI may yield improvements in patient outcomes, resource allocation, and cost. LEVEL OF EVIDENCE: Level II, diagnostic study.

Positive Blood Cultures in Periprosthetic Joint Infection Decrease Rate of Treatment Success.

BACKGROUND: Blood cultures are often obtained at the time of periprosthetic joint infection (PJI) diagnosis yet they are not considered part of the diagnostic criteria and the effects of a positive result on surgical outcome are unknown. The purposes of this study are to characterize the use of blood cultures when diagnosing PJI and to determine the association of positive blood cultures with PJI treatment success. METHODS: A retrospective chart review on 320 patients surgically treated for primary hip and knee PJIs was performed from 2006-2013 at 2 academic medical centers with minimum 12-month follow-up. Treatment success was defined by the Delphi criteria. Multiple logistic regression analysis was performed to identify variables associated with treatment success. RESULTS: Blood cultures were obtained from 53.1% of PJI patients (170/320) at the time of diagnosis. The same organism was identified 86.0% of the time in blood culture and operative culture. Patients with positive blood cultures at the time of PJI diagnosis had elevated synovial white blood cell count (98,979, P = .012), elevated serum C-reactive protein (24.2 mg/L, P < .001), and decreased treatment success (65.1%) compared with those with a negative blood culture (85.0%) and those without a blood culture (82.7%, P = .013). A positive blood culture remained associated with decreased PJI treatment success using multiple logistic regression analysis. CONCLUSION: The presence of positive blood cultures at the time of PJI diagnosis decreased PJI treatment success. Further prospective studies are needed to help identify the role of blood cultures in the work up of PJI and treatment optimization in these patients.

Gram Stain is Not Clinically Relevant in Treatment of Pediatric Septic Arthritis.

BACKGROUND: The diagnosis of pediatric septic arthritis (SA) can be challenging due to wide variability in the presentation of musculoskeletal infection. Synovial fluid Gram stain is routinely obtained and often used as an initial indicator of the presence or absence of pediatric SA. The purpose of this study was to examine the clinical utility of the Gram stain results from a joint aspiration in the diagnosis and management of pediatric SA. METHODS: All patients with suspected SA who underwent arthrocentesis and subsequent surgical irrigation and debridement at an urban tertiary care children's hospital between January 2007 and October 2016 were identified. Results of the synovial fluid Gram stain, as well as synovial cell count/differential and serum markers, were evaluated. RESULTS: A total of 302 patients that underwent incision and drainage for suspected SA were identified. In total, 102 patients (34%) had positive synovial fluid cultures and 47 patients (16%) had a microorganism detected on Gram stain. Gram stain sensitivity and specificity for the detection of SA were 0.40 and 0.97, respectively. This yielded a number needed to misdiagnose of 4.5 (ie, every fifth patient was misdiagnosed by Gram stain). For gram-negative organisms, the sensitivity dropped further to 0.13, with only 2/16 gram-negative organisms identified on Gram stain. Stepwise regression showed that age, serum white blood cell, and absolute neutrophil count were significant independent predictors for having a true positive Gram stain result. Elevated synovial white blood cell count was a significant predictor of having an accurate (culture matching the Gram stain) result. CONCLUSIONS: The Gram stain result is a poor screening tool for the detection of SA and is particularly ineffective for the detection of gram-negative organisms. The clinical relevance of the Gram stain and cost-effectiveness of this test performed on every joint aspiration sent for culture requires additional evaluation. Patients with gram-negative SA may be at high risk for inadequate coverage with empiric antibiotics due to poor detection of gram-negative organisms on initial Gram stain. LEVEL OF EVIDENCE: Level III-case-control study.

Utility of Serological Markers for Detecting Persistent Infection in Two-Stage Revision Arthroplasty in Patients With Inflammatory Arthritis.

BACKGROUND: Serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are commonly used for the diagnosis of persistence of infection after the first stage of 2-stage revision arthroplasty for periprosthetic joint infection (PJI). As both ESR and CRP are markers of systemic inflammation, the utility of these tests to monitor infection clearance in patients with inflammatory arthritis is unclear. METHODS: From 2001 to 2016, 44 two-stage revision total hip or knee arthroplasties in patients with an inflammatory arthritis diagnosed by a rheumatologist were identified. Persistence of infection at the time of planned second stage was defined as satisfying the Musculoskeletal Infection Society criteria for PJI (14 infected, 30 noninfected). ESR and CRP values were compared between the stages using nonparametric tests. Receiver operating characteristic analysis was performed to obtain the diagnostic parameters. RESULTS: ESR and CRP decreased between the stages in the noninfected group (ESR: mean decrease = 31.6 mm/h [19.2-44.0], P < .001; CRP: mean decrease = 5.2 mg/dL [2.1-8.2], P < .001), but remained elevated in the infected group (ESR: mean decrease = 7.7 [-23.1 to 36.6], P = .572; CRP: mean decrease = 1.5 [-2.2 to 5.1], P = .258). Optimal thresholds for persistent infection were 29.5 mm/h and 2.8 mg/dL, respectively, for ESR and CRP. The sensitivity and specificity at the optimal thresholds were 64% and 77% for ESR, and 64% and 90% for CRP. CONCLUSION: ESR and CRP responded to the treatment of PJI in patients with inflammatory arthritis and had reasonably high specificities with moderate sensitivities. ESR and CRP appear to be useful tools in diagnosing persistent infection even in patients with inflammatory arthritis.

Diagnosing Periprosthetic Joint Infection in Inflammatory Arthritis: Assumption Is the Enemy of True Understanding.

BACKGROUND: Despite concern over the interpretation of serum and synovial fluid tests to screen and diagnose periprosthetic joint infection (PJI) in patients with inflammatory arthritis, only a single study has investigated this area. We aimed to assess accuracy of clinical and laboratory markers for PJI diagnosis in the context of underlying inflammatory arthritis. METHODS: This multicenter study was conducted on total joint arthroplasty patients at 3 different centers between 2001 and 2016. PJI was defined based on Musculoskeletal Infection Society criteria. Acute PJI cases were excluded. Patients operated for a diagnosis other than infection, who did not subsequently fail at 1-year follow-up, were considered aseptic revisions. Serum C-reactive protein and erythrocyte sedimentation rate, synovial white blood cell and differential, as well as alpha-defensin and results of frozen section were documented. RESULTS: In total, 1220 patients undergoing revision total joint arthroplasty (567 PJI, 653 aseptic) were included. Fifty-five septic patients and 61 in the aseptic group had inflammatory arthritis. Although mean levels of serum C-reactive protein and synovial white blood cell in inflammatory arthritis patients were significantly higher compared to patients without inflammatory arthritis, there were no significant differences in PJI patients. The thresholds associated with increased risk for PJI in patients with and without inflammatory arthritis were similar and closely resembled traditional cut-points. CONCLUSION: We demonstrate higher baseline immune upregulation in aseptic revision cases with inflammatory arthritis, but no significant differences are seen for PJI. Conventional PJI thresholds for serum and synovial diagnostic markers should be adhered to. Assumptions about inflammatory arthritis patients needing differential diagnostic protocols should be avoided.

Early diagnosis of septic arthritis in immunocompromised patients.

OBJECTIVES: Septic arthritis results in rapid joint destruction if not properly diagnosed and treated. A work up for septic arthritis includes a peripheral white blood cell count, inflammatory markers, and a joint aspiration. In the general population, the interpretation of these labs has been well-defined by prior studies. To this point, no study has determined how immunosuppressive states affect this work up. METHODS: Patients with immunosuppressive conditions who received a joint aspiration for a painful joint were retrospectively identified. Laboratory results from their work up were gathered and analyzed. RESULTS: 216 patients were included in the study, 21 of whom were diagnosed with septic arthritis. The average aspiration WBC count was 74,190 with 88% PMNs. 81% had a positive gram stain. DISCUSSION: Laboratory values for immunosuppressed patients with septic arthritis were similar to those associated with septic arthritis in historical general population controls.

Diagnostic accuracy of interleukin-6 and procalcitonin in patients with periprosthetic joint infection: a systematic review and meta-analysis.

PURPOSE: Many studies have found associations between laboratory biomarkers and periprosthetic joint infection (PJI), but it remains unclear whether these biomarkers are clinically useful in ruling out PJI. This meta-analysis compared the performance of interleukin-6 (IL-6) versus procalcitonin (PCT) for the diagnosis of PJI. METHODS: In this meta-analysis, we reviewed studies that evaluated IL-6 or/and PCT as a diagnostic biomarker for PJI and provided sufficient data to permit sensitivity and specificity analyses for each test. The major databases MEDLINE, EMBASE, the Cochrane Library, Web of Science, and SCOPUS were searched for appropriate studies from the earliest available date of indexing through February 28, 2017. No restrictions were placed on language of publication. RESULTS: We identified 18 studies encompassing a total of 1,835 subjects; 16 studies reported on IL-6 and 6 studies reported on PCT. The area under the curve (AUC) was 0.93 (95% CI, 0.91-0.95) for IL-6 and 0.83 (95% CI, 0.79-0.86) for PCT. The pooled sensitivity was 0.83 (95% CI, 0.74-0.89) for IL-6 and 0.58 (95% CI, 0.31-0.81) for PCT. The pooled specificity was 0.91 (95% CI, 0.84-0.95) for IL-6 and 0.95 (95% CI, 0.63-1.00) for PCT. Both the IL-6 and PCT tests had a high positive likelihood ratio (LR); 9.3 (95% CI, 5.3-16.2) and 12.4 (95% CI, 1.7-89.8), respectively, making them excellent rule-in tests for the diagnosis of PJI. The pooled negative LR for IL-6 was 0.19 (95% CI, 0.12-0.29), making it suitable as a rule-out test, whereas the pooled negative LR for PCT was 0.44 (95% CI, 0.25-0.78), making it unsuitable as a rule-out diagnostic tool. CONCLUSIONS: Based on the results of the present meta-analysis, IL-6 has higher diagnostic value than PCT for the diagnosis of PJI. Moreover, the specificity of the IL-6 test is higher than its sensitivity. Conversely, PCT is not recommended for use as a rule-out diagnostic tool.

Role of Th17 and Treg cells in septic arthritis and the impact of the Th17/Treg -derived cytokines in the pathogenesis of S. aureus induced septic arthritis in mice.

Intravenous inoculation of Swiss mice with S. aureus leads to severe synovial joint tissue swelling along with prominent T lymphocyte infiltrate with associated inflammation in synovial tissue. Cytokines released from macrophages such as TNF-α, IL-1ß and IL-6 the main players that precede cartilage and bone destruction during septic arthritis (SA) followed by osteoclast differentiation and bone resorption. CD4+ naïve T cells upon cytokine driven activation, differentiate into lineages of helper (Th) and regulatory T cells (Treg) including inflammatory Th17 cell lineage. Acting as counterbalance, Tregs protect the host by releasing anti-inflammatory IL-10. A disturbed balance between Th17 and Treg cell development skews the pathways towards Th17 lineage, but how it actually induces SA is still unexplored. Therefore, this study has been attempted to demonstrate the Th17/Treg ratio in synovial tissue, spleen and peripheral blood by FACS and their derived cytokines from serum of arthritic mice. Here, we reported that the ratios of Th17/Treg as well as their related cytokine levels were increased at 3 days post-infection which was decreased during 9 DPI but heightened again at 15DPI resulting in persistence of the disease, though decreased again at 30 DPI even in animals with increased dose of infection. Bacterial colonies were present in synovial joints at 15 DPI in animals with increased infection but found to be absent at 30 DPI. Maintaining Th17/Treg balance by neutralizing functionally active Th17 and their related cytokines or adoptive transfer of fully active Tregs and/or their related cytokines may lead to a novel therapeutic strategy for combating Staphylococcal arthritis.