Diagnostic accuracy of the leukocyte esterase test for native joint septic arthritis and prosthetic joint infections: a systematic review and meta-analysis.

Irrigation and Debridement

Introduction: Coronavirus Disease (COVID-19) is a highly infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has infected many people all over the world. One of the best ways to lessen its spread is through early detection and diagnosis. Various serological tests are now being used as a surveillance tool in the detection of antibodies as a response to SARS-CoV-2. The aim of this study is to evaluate the diagnostic accuracy and performance of the available COVID-19 antibody tests authorized by the Food and Drug Administration (FDA) Philippines that make use of Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescence Immunoassay (CLIA) and Lateral Flow Immunoassay (LFIA). Method: Complete published journal articles relevant to the diagnostic accuracy of the three antibody tests were collected using trusted medical journal search engines. The quality of journals was assessed using QUADAS-2 to determine the risk of bias and assess the applicability judgments of diagnostic accuracy studies. Forest plots were used to summarize the performance of LFIA, ELISA and CLIA according to their specificity and sensitivity in detecting various antibodies. Pooled sensitivity and specificity were also done using bivariate random-effects models with its log-likelihood, a corresponding chi-square test statistic, and area under the summary Receiver-Operating Characteristic curve to see the potential heterogeneity in the data and to assess the diagnostic accuracy of the COVID-19 antibody tests. Results: Bivariate random-effects model and areas under the sROC curve were used to evaluate the diagnostic accuracy of COVID-19 antibody tests. The pooled sensitivity in detecting IgG based on CLIA, ELISA, and LFIA were 81.7%, 58.7%, and 74.3% respectively, with an overall of 72.0%. For IgM detection, LFIA has a higher pooled sensitivity of 69.6% than CLIA with 61.0%. Overall, the pooled sensitivity is 68.5%. In IgA detection, only ELISA based test was included with a pooled sensitivity of 84.8%. Lastly, pooled sensitivities for combined antibodies based on ELISA and LFIA were 89.0% and 81.6% respectively, with an overall of 82.5%. On the other hand, all tests excluding ELISA-IgA displayed high pooled specificities with a range of 94.0% to 100.0%. Diagnostic accuracies of the test in detecting IgG, IgM, and combined antibodies were found out to be almost perfect based on the computed area under the sROC with values of 0.973, 0.953, and 0.966, respectively. Conclusion: In this systematic review and meta-analysis, existing evidence on the diagnostic accuracy of antibody tests for COVID-19 were found to be characterized by high risks of bias, consistency in the heterogeneity of sensitivities, and consistency in the homogeneity of high specificities except in IgA detection using ELISA. The bivariate random-effects models showed that there are no significant differences in terms of sensitivity among CLIA, ELISA and LFIA in detecting IgG, IgM, and combined antibodies at a 95% confidence interval. Nonetheless, CLIA, ELISA and LFIA were found to have excellent diagnostic accuracies in the detection of IgG, IgM and combined antibodies as reflected by their AUC values. Doi: 10.28991/SciMedJ-2021-0304-1 Full Text: PDF

BackgroundForming large cohorts to study prosthetic joint infections (PJIs) is a challenge without an existing surgical registry, as is the case in Canada. Administrative databases are an option, yet PJI diagnostic codes are insensitive. There is a need to improve the detection of PJIs from within administrative databases.MethodsIndividuals who had a primary arthroplasty at four hospitals in Toronto, Canada from 2010 to 2016 were identified using Canadian Classification of Health Intervention codes (based on the International Classification of Disease, Tenth Revision). Each re-admission to the same hospital until December 31, 2016 was reviewed for the presence of a PJI. The performance characteristics (sensitivity, specificity, positive and negative predictive values) of combinations of diagnostic and procedure codes when compared with the gold standard of chart review were calculated. The primary outcome was the algorithm that maximized sensitivity and positive predictive value.Results27,843 primary arthroplasties were performed with 8595 readmissions, of which 572 involved a PJI. Median follow-up was 1258 days (interquartile range (IQR) 614–1891 days), with median time to first re-admission of 352 days (IQR range 166–725 days). PJI codes exhibited a sensitivity of 0.86 (95% confidence interval (95% CI) 0.83–0.89) and positive predictive value (PPV) of 0.89 (95% CI 0.86–0.92). The best performing algorithm is a combination of a PJI code or joint spacer insertion procedure code or insertion of a peripherally inserted central catheter along with an arthroplasty code (sensitivity 0.90, 95% CI 0.88–0.93 and PPV 0.89, 95% CI 0.86–0.91). Using timing from primary arthroplasty, spacer insertion codes and presence of a subsequent arthroplasty procedure code identified 68% (71/105) of first stage and 74% (108/146) of debridement with joint retention procedures during the first re-admission for a PJI.ConclusionCombinations of diagnosis and procedure codes can reliably identify PJIs from administrative databases. Individual orthopaedic procedure codes and timing from primary arthroplasty can inform the surgical procedure performed. This PJI detection algorithm could be used for PJI surveillance and research.DisclosuresAll authors: No reported disclosures.

Introduction Bone and Joint Infections (BJI) are medically important, costly and occur in native and prosthetic joints. Arthroplasties will increase significantly in absolute numbers over time as well as the incidence of Prosthetic Joint Infections (PJI). Diagnosis of BJI and PJI is sub-optimal. The available diagnostic tests have variable effectiveness, are often below standard in sensitivity and/or specificity, and carry significant contamination risks during the collection of clinical samples. Improvement of diagnostics is urgently needed. Areas covered We provide a narrative review on current and future diagnostic microbiology technologies. Pathogen identification, antibiotic resistance detection, and assessment of the epidemiology of infections via bacterial typing are considered useful for improved patient management. We confirm the continuing importance of culture methods and successful introduction of molecular, mass spectrometry-mediated and next-generation genome sequencing technologies. The diagnostic algorithms for BJI must be better defined, especially in the context of diversity of both disease phenotypes and clinical specimens rendered available. Expert opinion Whether interventions in BJI or PJI are surgical or chemo-therapeutic (antibiotics and bacteriophages included), prior sensitive and specific pathogen detection remains a therapy-substantiating necessity. Innovative tests for earlier and more sensitive and specific detection of bacterial pathogens in BJI are urgently needed.

Patients treated for early prosthetic joint infection (PJI) with surgical debridement, prosthesis retention and biofilm-active antibiotics, such as rifampicin or fluoroquinolones have a rate of successful infection eradication that is similar to patients treated with the traditional approach of prosthesis exchange. It is therefore important to consider other outcomes after PJI treatment that may influence management decisions, such as function, quality of life (QOL) and treatment-associated complications. To describe rates of successful treatment for patients with PJI undergoing surgical debridement, prosthesis retention and biofilm-active antibiotics and compare their functional outcomes, QOL and complication rates to patients without PJI. Nineteen patients treated for PJI after hip arthroplasty with debridement, prosthesis retention and biofilm-active antibiotics were matched to 76 controls who underwent hip arthroplasty with no infection. Cumulative survival free from treatment failure at 2 years was 88% (95% confidence interval, 59-97%). PJI cases had significant improvement from pre-arthroplasty to 12-months post-arthroplasty in function according to Harris Hip Score and QOL according to the 12-item Short Form Health Survey Physical Component Summary. There was no significant difference in the improvement between controls and cases. PJI was not a risk factor for poor function or QOL. Medical complications occurred more frequently in cases (6/19 (32%)) than controls (9/76 (12%); P = 0.04), with this difference being accounted for by drug reactions. Surgical complications were the same in the two groups. Treatment of PJI with debridement, prosthesis retention and biofilm-active antibiotics is successful, well tolerated and results in significant improvements in function and QOL, which are similar to patients without PJI.

Klebsiella pneumoniae has the ability to form biofilm; therefore, the treatment of prosthetic joint infection involving K. pneumoniae is often challenging. This report describes the first case of acute hematogenous prosthetic knee joint infection with K. pneumoniae that occurred as a result of an asymptomatic gallbladder abscess. The patient was a 78-year-old man who underwent bilateral total knee arthroplasty 6 years ago. He had pain and swelling in his right knee. The synovial fluid culture of the right knee revealed K. pneumoniae and prosthetic joint infection was diagnosed. Computed tomography revealed a gallbladder abscess in the absence of right upper abdominal pain. The patient underwent simultaneous debridement of the knee and open cholecystectomy. The treatment was successful and the prosthesis was retained. In cases of hematogenous prosthetic joint infection with K. pneumoniae, other sources of infection should be suspected and investigated regardless of whether they are symptomatic.

BackgroundKnee arthroplasty is an orthopedic surgical procedure in which a damaged joint is replaced with an artificial one. It is estimated that 1–2% of knee arthroplasties will encounter infection over their lifetime. Although α-hemolytic Streptococcus species play an important role in prosthetic joint infection, they are less common than staphylococcal species.Case presentationIn this report, a 50-year-old Iranian woman was diagnosed with prosthetic knee joint infection based on clinical, radiological, and laboratory findings. She was diabetic and had undergone a left total knee arthroplasty, which, 18 months after the surgery, presented pain, erythema, and edema in that knee. The primary culture of knee aspirate was positive for α-hemolytic Streptococcus species, but following antibiotic medication, culture was negative. The primary antibiotic regime was vancomycin and meropenem, which was changed to cefepime for the management of the infection based on the results of antimicrobial susceptibility testing.ConclusionsThis report indicated the clinical presentation and management of the patient with prosthetic joint infection in which the patient recovered without any severe complications or surgical intervention.

Two-stage revision including interval cement spacer application is the gold standard treatment for both prosthetic and native hip infection with joint destruction. We present a summarised case series of our experience of successfully treating 8 infected joints in 6 patients treated with 2-stage revision using interval static spacers. Two patients with 3 native joint infections and 4 patients with 5 prosthetic joint infections were treated with 2-stage arthroplasty with interval static spacer application consisting of static block spacers or cement beads. There were 2 females and 4 males. Mean age is 40.5 years and range 24-60 years. Mean interval between the first and second stage is 8weeks. One case has not undergone the second stage as he is unable to fund the operation. Organisms cultured include methicillin- sensitive staphylococcus aureus, enterococcus. All underwent cementless hip reconstruction with one patient undergoing hybrid hip reconstruction. At mean 36-month follow-up (range 30-44 months) all patients have normalized inflammatory markers and improvement in Oxford hip score (OHS) from pre-operative mean 16.6 (range 15-19) and post-operative mean OHS 43.7 (range 35-50). Patients continue to be followed up. We recommend this cement spacer option as part of a 2-stage procedure when faced with moderate to severe acetabular bone loss. It is effective in treating native or prosthetic hip joint infections and joint infections in patients with sickle cell haemoglobinopathy.

BackgroundJoint replacement is an effective intervention and prosthetic joint infection (PJI) is one of the most serious complications of such surgery. Diagnosis of PJI is often complex and requires multiple modalities of investigation. We describe a rare cause of PJI which highlights these challenges and the role of whole-genome sequencing to achieve a rapid microbiological diagnosis to facilitate prompt and appropriate management.Case presentationA 79-year-old man developed chronic hip pain associated with a soft-tissue mass, fluid collection and sinus adjacent to his eight-year-old hip prosthesis. His symptoms started after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. Synovasure™ and 16S polymerase chain reaction (PCR) tests were negative, but culture of the periarticular mass and genome sequencing diagnosed BCG infection. He underwent a two-stage joint revision and a prolonged duration of antibiotic therapy which was curative.ConclusionsBCG PJI after therapeutic exposure can have serious consequences, and awareness of this potential complication, identified from patient history, is essential. In addition, requesting appropriate testing is required, together with recognition that traditional diagnostics may be negative in non-pyogenic PJI. Advanced molecular techniques have a role to enhance the timely management of these infections.

Introduction: Revision total hip arthroplasty is a surgical challenge when undertaken for hip prosthetic joint infection (PJI). When PJI occurs in the setting of severe proximal femoral bone loss, proximal femoral replacement (PFR) can serve as an effective salvage strategy, restoring function in prosthetic hips that cannot be reconstructed otherwise.Materials and methods: This retrospective series from a high-volume revision hip surgeon comprises 15 PFRs in 14 patients. Infection was the indication for surgery in all cases. Thirteen patients had confirmed PJI as per the 2018 Musculoskeletal Infection Society (MSIS) criteria. The primary outcome measure was the eradication of infection. Secondary outcome measures included peri- and postoperative complications, re-operation, mobility, and death. The mean follow-up was three years.Results: Infection was eradicated in 13 cases (86.6%). Of the two cases with infection, one was asymptomatic for seven years before PJI became evident again. Complications included hip dislocation (three episodes in two patients). One patient underwent revision of the acetabular component due to infected loosening. All but one patient were ambulatory with walking aids. Both patients with persistent or recurrent infection subsequently died.Conclusions: PFR is an option for patients with PJI for whom standard revision hip arthroplasty would be unsuitable and excision surgery unacceptable. This study suggests promising results for the eradication of PJI using PFR as a salvage procedure in this particularly challenging cohort.Level of evidence: The study is classified as level IV evidence.

BackgroundA combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI.MethodsA prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas.ResultsOne hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001.ConclusionFor early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of delayed and 94.8% of late cases are diagnosed. The conjunction of histopathology and sonicate fluid culture yields a sensitivity of 100% for all types of infection.

BackgroundReinfection rates after two-stage revision (TSR) for prosthetic joint infection (PJI) range from 7.9 to 14%. Many factors, including sinus tracts, are associated with reinfection after this procedure. This study aimed to delineate whether the presence of sinus tract could increase reinfection rate after TSR and to investigate other potential risk factors for reinfection after TSR.MethodsWe conducted a case-control study by retrospectively reviewing patients who underwent TSR for prosthetic hip joint infection from 2002 to 2022. The case group included patients who developed reinfection after TSR, while the control group consisted of patients who did not experience reinfection. PJI and reinfection after TSR were defined based on Delphi-based international consensus criteria. Patient demographics, past medical history, clinical manifestations, laboratory results, interval between stages, microbiological culture results were collected. Univariate analyses were utilized to assess the effect of sinus tract on reinfection and to identify other risk factors for reinfection after TSR.ResultsSix patients with reinfection after TSR were included as the case group and 32 patients without reinfection were in the control group. Significant difference was observed in percentage of patients with sinus tracts between the two groups (67% in the case group versus 19% in the control group, p = 0.031, OR = 8.7). Significant difference was also found in percentage of patients with positive cultures of synovial fluid and synovium harvested during the first-stage revision between the two groups (100% in the case group versus 50% in the control group, p = 0.030). Additionally, patients in the case group had a significantly higher C-reactive protein (CRP) level prior to the second stage revision than that of patients in the control group (8.80 mg/L versus 2.36 mg/L, p = 0.005), despite normal CRP levels in all patients.ConclusionsOur study revealed that the presence of sinus tracts could significantly increase risk of postoperative reinfection after TSR. Positive cultures during the first stage revision and elevated CRP level prior to the second stage revision could also increase the risk of reinfection after TSR. Further studies with a larger sample size are required.Trial registrationRetrospectively registered.

Cutibacterium avidum has recently been reported as a rare cause of prosthetic joint infections (PJIs), contrary to Cutibacterium acnes, which is well established as a cause of PJIs, especially in shoulder arthroplasties. Two specific risk factors for PJI due to C. avidum have been reported: obesity and the skin incision approach. Here, we report four cases of hip PJIs caused by C. avidum admitted over a 30-month period at a single center. Whole-genome sequencing revealed that the four C. avidum strains were all individual strains and did not originate from a common source, such as an outbreak. Antibiotic susceptibility tests showed that the isolates were fully susceptible, and none carried known antibiotic resistance genes. In conclusion, the occurrence of four cases of PJI caused by C. avidum over a limited time at a single center may indicate that this pathogen is underestimated and is either emerging or more common than previously recognized. The patients presented overt signs of infection during surgery, indicating that C. avidum is a virulent pathogen. None of the previously reported risk factors for C. avidum PJI applied to these patients as only one was obese and none were operated on using a direct anterior skin incision approach.

Objectives:We described the clinical outcomes and estimated cost savings from switching patients to early oral therapy from intravenous (IV) therapy for prosthetic joint infections (PJI) based on predefined criteria.Methods:Retrospective observational study in a large health authority consisting of 12 acute care hospitals in Canada. Patient demographics, microbiological and treatment data were collected for all patients with first episode of knee or hip PJI in 2022. Treatment failure rates, allergic or adverse reactions to IV or oral treatment, and hospital readmission rates were reported for those who met criteria for early switch to oral therapy.Results:Fifty-one patients were included. Thirty-seven patients (73%) had knee PJI, with debridement, antibiotics, and implant retention being the most common procedure. Sixteen patients (31%) had IV therapy for the entire duration of treatment, and the mean duration was 44 days. Twenty-three patients (45%) could have been switched to oral therapy. In practice however, only 3 patients (6%) were switched to oral therapy by day 7 following surgical source control. Five patients (22%) had clinical and/or microbiological failure 2 years postsurgery. Four patients (17%) and 6 patients (26%) developed an allergic or adverse reaction to IV and oral therapy, respectively. Five patients (22%) developed line complications. We estimated potential cost savings of almost $70,000 Canadian dollars with early oral therapy.Conclusion:Almost half of our PJI patients could have been switched to oral therapy within 7 days post-surgical source control. This study highlights a great opportunity for antimicrobial stewardship.

Background Cutibacterium acnes is an emerging pathogen in bone and joint infections. While treatment guidelines recommend the use of β-lactam therapy for C. acnes infections, the lack of routine susceptibility testing may result in wide variation in treatment regimens among physicians. We assessed the treatment regimens chosen by physicians for patients with bone and joint infections with C. acnes and the treatment outcomes of β-lactam and non-β-lactam regimens. Methods This was a multi-center, historical cohort study comparing treatment regimens in patients diagnosed with C. acnes for both native and prosthetic bone and joint infection. The study included patients with monomicrobial cultures positive for C. acnes and diagnosed with septic arthritis, prosthetic joint infections, osteomyelitis, or discitis between 7/1/2018- 6/30/2023. Data collected included antimicrobial therapeutic regimens, surgical intervention, as well as treatment failure and success. Data were analyzed using chi square test, Student’s t-test, and the Mann-Whitney U test. Results Among 49 included patients, 65.3% of infections resulted from prosthetic joint infection, 26.5% from osteomyelitis, and 8.2% from septic arthritis. The most common intravenous antibiotics chosen to treat C. acnes were ceftriaxone (51%), vancomycin (16.3%), and penicillin (6.1%) with a mean treatment duration of 43.4 days. The most common oral antibiotic treatment was doxycycline (20.4%), amoxicillin (18.4%), cephalexin/cefadroxil (12.2%) with a median outpatient treatment duration of 38 days (range 5, 364). Overall, there were no difference in treatment outcomes between patients treated with β-lactams vs, non-β-lactams at six months, including cure (58.8% vs. 71.4%, p=0.53), persistence of symptoms (26.5% vs. 14.3%, p=0.49), recurrence (17.6% vs. 28.5%, p=0.51), and requiring suppressive therapy (23.5% vs. 28.6%, p=0.78), respectively. Conclusion Physicians preferred β-lactam antibiotics for treating patients with bone and joint infections caused by C. acnes. There were no differences in outcomes for treating C. acnes bone and joint infections between β-lactam and non-β-lactam antibiotic regimens. Further studies should be performed to confirm this observation. Disclosures All Authors: No reported disclosures