Eschar in a Belgian traveler returning from Central Europe.

BACKGROUND: Tularemia is a zoonotic infection caused by Francisella tularensis, an aerobic, facultative intracellular coccobacillus, encountered especially in the Northern hemisphere. F. tularensis is a pathogen of humans and hundreds of animal species. PATIENTS AND METHODS: A Belgian traveler returning from an adventurous vacation in Central Europe presents fever, flu-like symptoms, a skin ulcer with a necrotic center resembling an eschar on the left thigh and painful left inguinal lymphadenopathy. An enzyme linked immunosorbent assay developed by the National Reference Laboratory for Tularemia, Sciensano, Belgium, detected elevated Ig G antibodies against F. tularensis, while the rest of the serologies were negative. RESULTS: A highly likely case of ulceroglandular tularemia is described and the differential diagnosis is discussed. CONCLUSION: The incidence of tularemia has been increasing throughout Europe in recent years. Physicians should be aware of this disease, its diversity of reservoirs, transmission routes and clinical presentations.

Laboratory workflow for optimizing leukocyte count and differential in synovial fluids on Sysmex XN-1000.

INTRODUCTION: Falsely elevated synovial white blood cell (WBC) counts using automated hematology analyzers have been reported particularly in the setting of joint arthroplasty. We evaluated the implementation of a laboratory workflow based on Sysmex XN-1000-automated cell counting and scattergram interpretation. METHODS: WBC and differential were measured for 76 synovial fluid samples (29 native joints and 47 with joint arthroplasties) with Sysmex XN-1000 and manual methods. All scattergrams were evaluated for possible incorrect WBC and/or differential according to our implemented workflow. A specific finding was the "banana-shape" scattergram, which indicates possible interferences. The European Bone & Joint Infection Society (EBJIS) criteria were applied to identify possible prosthetic joint infections (PJIs) in patients with joint arthroplasties. RESULTS: Correlation between automated and manual WBC counts, calculated for samples with WBC count <50 000/µL, was higher for native joints (r = 0.938) compared with patients known with arthroplasty (r = 0.906). Scattergrams classified as OK showed overall a higher correlation compared with scattergrams, which were interpreted as NOT OK. "Banana-shape" scattergrams (n = 19) showed falsely elevated automated WBC count, and the patterns were mainly seen in prosthesis patients (17/19 [89%]). Six of 47 (13%) patients with joint arthroplasties were reclassified from "confirmed" to "unlikely" PJI according to the EBJIS criteria. CONCLUSION: Our workflow based on scattergram interpretation resulted in accurate WBC counts in synovial fluid using automated/and or manual methods. It is important to identify the presence of "banana-shape" scattergrams to avoid overestimated automated WBC counts. Overall, automated synovial WBC count can be used, even for patients with arthroplasty, but after visual inspection of the scattergram to exclude possible interferences.

The global burden of fracture-related infection: can we do better?

Fracture-related infection is a major complication related to musculoskeletal injuries that not only has important clinical consequences, but also a substantial socioeconomic impact. Although fracture-related infection is one of the oldest disease entities known to mankind, it has only recently been defined and, therefore, its global burden is still largely unknown. In this Personal View, we describe the origin of the term fracture-related infection, present the available data on its global impact, and discuss important aspects regarding its prevention and management that could lead to improved outcomes in both high-resource and low-resource settings. We also highlight the need for health-care systems to be adequately compensated for the high cost of human resources (trained staff) and well-equipped facilities required to adequately care for these complex patients. Our aim is to increase awareness among clinicians and policy makers that fracture-related infection is a disease entity that deserves prioritisation in terms of research, with the goal to standardise treatment and improve patient outcomes on a global scale.

Should treatment decisions in septic arthritis of the native hip joint be based on the route of infection?

Background: Surgical management of septic arthritis (SA) of the hip aims at treating the infection by either preserving, resecting or replacing the joint. In some cases, joint preservation should be attempted, whereas other cases would benefit from immediate joint resection or replacement. Prognostic factors have been proposed to guide decision-making. We hypothesized that most of these factors can be simplified to three subgroups based on the route of infection: contiguous spreading, direct inoculation or hematogenous seeding. Methods: A total of 41 patients have been treated surgically for SA of the native hip at our tertiary hospital during the last 16 years. Medical records were studied, and various patient and disease characteristics were collated. Results: Significant differences between (1) level of fitness, (2) condition of the hip joint, (3) micro-organisms and (4) chance of femoral head preservation were found for patients with SA of the native hip resulting from the three aforementioned subgroups. Femoral head resection was necessary at one point in 85 % of patients. Patients with hematogenous infections of undamaged hips had a reasonable chance (53 %) of avoiding joint resection or replacement. Hip arthroplasty was performed on 46.3 % of patients, with an infection rate of 10.5 %. Conclusion: Patients with SA of the native hip resulting from contiguous spreading, hematogenous seeding or direct inoculation differ significantly and should be considered distinct clinical entities. Route of infection is directly related to the chance of femoral head preservation and should, therefore, guide decision-making. Only patients with hematogenous infection to a previously healthy hip had the possibility of femoral head preservation.

The role of sonication in the diagnosis of periprosthetic joint infection in total shoulder arthroplasty.

An increased sensitivity of sonication compared to periprosthetic tissue cultures in the diagnosis of periprosthetic joint infection (PJI) of hip and knee arthroplasty has been reported. The goal of this study was to determine if there is also an added value of implant sonication in the diagnosis of PJI in total shoulder arthroplasty (TSA). A retrospective analysis of patients who underwent removal of their TSA combined with sonication of the implant for suspicion of PJI between April 2009 and August 2017 was performed. The diagnosis of PJI was based on the major criteria described by Parvizi. We calculated sensitivity, specificity, predictive values, likelihood ratios and diagnostic accuracy for sonication cultures in comparison with periprosthetic tissue cultures. Data from 41 patients were analysed. Standard synovial fluid cultures combined with intraoperative periprosthetic tissue cultures had a sensitivity of 95%, specificity of 95% and total accuracy of 95%. Sonication cultures had a sensitivity of 91%, specificity of 68% and total accuracy of 80%. Six patients had negative standard cultures but positive sonication cultures. In patients with only one positive standard culture, the pathogen of the sonication culture corresponded to the pathogen of the positive soft tissue culture. We found a possible added value of sonication of TSA in the diagnosis of PJI in conjunction with standard intraoperative cultures. In some patients with suspicion of low-grade TSA infection, sonication could identify a possible causal microorganism despite negative standard cultures.

Stability of magistral phage preparations before therapeutic application in patients with chronic rhinosinusitis, sepsis, pulmonary, and musculoskeletal infections.

IMPORTANCE: As antimicrobial resistance becomes more prevalent, the application of (bacterio)phage therapy as an alternative treatment for difficult-to-treat infections is (re)gaining popularity. Over the past decade, numerous promising case reports and series have been published demonstrating the therapeutic potential of phage therapy. However, important questions remain regarding the optimal treatment protocol and, unlike for medicinal products, there are currently no predefined quality standards for the stability of phage preparations. Phage titers can be influenced by several factors which could lead to reduced titers after preparation and storage and, ultimately, subtherapeutic applications. Determining the stability of different phages in different recipients according to the route of administration is therefore one of the first important steps in establishing a standardized protocol for phage therapy.

Treatment and outcome of fracture-related infection of the clavicle.

INTRODUCTION: The number of operatively treated clavicle fractures has increased over the past decades. Consequently, this has led to an increase in secondary procedures required to treat complications such as fracture-related infection (FRI). The primary objective of this study was to assess the clinical and functional outcome of patients treated for FRI of the clavicle. The secondary objectives were to evaluate the healthcare costs and propose a standardized protocol for the surgical management of this complication. METHODS: All patients with a clavicle fracture who underwent open reduction and internal fixation (ORIF) between 1 January 2015 and 1 March 2022 were retrospectively evaluated. This study included patients with an FRI who were diagnosed and treated according to the recommendations of a multidisciplinary team at the University Hospitals Leuven, Belgium. RESULTS: We evaluated 626 patients with 630 clavicle fractures who underwent ORIF. In total, 28 patients were diagnosed with an FRI. Of these, eight (29%) underwent definitive implant removal, five (18%) underwent debridement, antimicrobial treatment and implant retention, and fourteen patients (50%) had their implant exchanged in either a single-stage procedure, a two-stage procedure or after multiple revisions. One patient (3.6%) underwent resection of the clavicle. Twelve patients (43%) underwent autologous bone grafting (tricortical iliac crest bone graft (n = 6), free vascularized fibular graft (n = 5), cancellous bone graft (n = 1)) to reconstruct the bone defect. The median follow-up was 32.3 (P25-P75: 23.9-51.1) months. Two patients (7.1%) experienced a recurrence of infection. The functional outcome was satisfactory, with 26 out of 28 patients (93%) having full range of motion. The median healthcare cost was € 11.506 (P25-P75: € 7.953-23.798) per patient. CONCLUSION: FRI is a serious complication that can occur after the surgical treatment of clavicle fractures. In our opinion, when treated adequately using a multidisciplinary patient-specific approach, the outcome of patients with an FRI of the clavicle is good. The median healthcare costs of these patients are up to 3.5 times higher compared to non-infected operatively treated clavicle fractures. Although not studied individually, we consider factors such as the size of the bone defect, condition of the soft tissue, and patient demand important when it comes to guiding our surgical decision making in cases of osseous defects.

Diagnosis of fracture-related infection in patients without clinical confirmatory criteria: an international retrospective cohort study.

Background: fracture-related infection (FRI) remains a serious complication in orthopedic trauma. To standardize daily clinical practice, a consensus definition was established, based on confirmatory and suggestive criteria. In the presence of clinical confirmatory criteria, the diagnosis of an FRI is evident, and treatment can be started. However, if these criteria are absent, the decision to surgically collect deep tissue cultures can only be based on suggestive criteria. The primary study aim was to characterize the subpopulation of FRI patients presenting without clinical confirmatory criteria (fistula, sinus, wound breakdown, purulent wound drainage or presence of pus during surgery). The secondary aims were to describe the prevalence of the diagnostic criteria for FRI and present the microbiological characteristics, both for the entire FRI population. Methods: a multicenter, retrospective cohort study was performed, reporting the demographic, clinical and microbiological characteristics of 609 patients (with 613 fractures) who were treated for FRI based on the recommendations of a multidisciplinary team. Patients were divided in three groups, including the total population and two subgroups of patients presenting with or without clinical confirmatory criteria. Results: clinical and microbiological confirmatory criteria were present in 77 % and 87 % of the included fractures, respectively. Of patients, 23 % presented without clinical confirmatory criteria, and they mostly displayed one (31 %) or two (23 %) suggestive clinical criteria (redness, swelling, warmth, pain, fever, new-onset joint effusion, persisting/increasing/new-onset wound drainage). The prevalence of any suggestive clinical, radiological or laboratory criteria in this subgroup was 85 %, 55 % and 97 %, respectively. Most infections were monomicrobial (64 %) and caused by Staphylococcus aureus. Conclusion: clinical confirmatory criteria were absent in 23 % of the FRIs. In these cases, the decision to operatively collect deep tissue cultures was based on clinical, radiological and laboratory suggestive criteria. The combined use of these criteria should guide physicians in the management pathway of FRI. Further research is needed to provide guidelines on the decision to proceed with surgery when only these suggestive criteria are present.

Use of negative pressure wound therapy in patients with fracture-related infection more than doubles the risk of recurrence.

PURPOSE: Fracture-related infection (FRI) is one of the most serious complications in orthopedic trauma surgery. Despite its widespread use, the role of Negative Pressure Wound Therapy (NPWT) remains controversial in the management pathway of FRI. The aim of this study was to assess the relationship between the application of NPWT and its duration and recurrence of infection in operatively treated FRI patients. PATIENTS AND METHODS: This is a retrospective cohort study based on the FRI database of three level 1 Trauma Centres. Included patients had to be at least 16 years of age and surgically treated for FRI between January 1st 2015 and September 1st 2020. Patients were subdivided in either the NPWT group, when NPWT was applied as part of the FRI treatment, or in the control group, when no NPWT had been applied. To limit confounding, patients were excluded if they (also) underwent NPWT prior to the diagnosis of FRI. The relation between the duration of NPWT during FRI treatment and the recurrence rate of infection was analyzed using a multivariable logistic regression model. RESULTS: A total of 263 patients were included, 99 in the NPWT group and 164 in the control group. The median duration of NPWT was 18.0 (IQR 15.8) days. In the NPWT group, 28 patients (28.3%) developed a recurrent FRI. In the control group, 19 patients (11.6%) had a recurrent FRI (p = 0.001, 95% CI [0.174 - 0.635]). In the NPWT group there were no significant differences in baseline characteristics between the recurrence and non-recurrence group. The duration of NPWT was associated with a higher risk of recurrence of infection (p = 0.013, OR 1.036, 95% CI [1.008 - 1.066]). CONCLUSION: Delayed wound closure with the application of NPWT increased the risk of recurrence of infection in patients with soft tissue defects after FRI treatment. Therefore, it is advised to consider NPWT only as a short-term (e.g. few days) necessity to bridge the period until definitive wound closure can be established.

Fracture-related infection.

Musculoskeletal trauma leading to broken and damaged bones and soft tissues can be a life-threating event. Modern orthopaedic trauma surgery, combined with innovation in medical devices, allows many severe injuries to be rapidly repaired and to eventually heal. Unfortunately, one of the persisting complications is fracture-related infection (FRI). In these cases, pathogenic bacteria enter the wound and divert the host responses from a bone-healing course to an inflammatory and antibacterial course that can prevent the bone from healing. FRI can lead to permanent disability, or long courses of therapy lasting from months to years. In the past 5 years, international consensus on a definition of these infections has focused greater attention on FRI, and new guidelines are available for prevention, diagnosis and treatment. Further improvements in understanding the role of perioperative antibiotic prophylaxis and the optimal treatment approach would be transformative for the field. Basic science and engineering innovations will be required to reduce infection rates, with interventions such as more efficient delivery of antibiotics, new antimicrobials, and optimizing host defences among the most likely to improve the care of patients with FRI.

The Microbiological Etiology of Fracture-Related Infection.

Purpose: Fracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI. Methods: FRI patients treated at the University Hospitals of Leuven, Belgium, between January 1st 2015 and November 24th 2019 were evaluated retrospectively. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2-10 weeks) or late-onset (> 10 weeks) FRI. Results: One hundred ninety-one patients with 194 FRIs, most frequently involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram negative bacilli (GNB) (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram positive cocci. Conclusion: This study revealed that in early FRIs, polymicrobial infections and infections including Enterobacterales and enterococcal species were more frequent. A time-based FRI classification is not meaningful to estimate the microbiological epidemiology and cannot be used to guide empiric antibiotic therapy. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy.

Clinical Efficacy and Safety of Vancomycin Continuous Infusion in Patients Treated at Home in an Outpatient Parenteral Antimicrobial Therapy Program.

Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of a structured vOPAT program implemented in the University Hospitals Leuven. The program provides continuous elastomeric infusion of vancomycin at home with biweekly follow-up at the outpatient clinic. Demographics, clinical, biochemical and treatment parameters, target attainment parameters and clinical outcomes were recorded. An e-survey was conducted to assess patient satisfaction. Thirty-five vOPAT episodes in 32 patients were included. During 206 follow-up consultations, 203 plasma concentration measurements were registered with a median vancomycin plasma concentration of 22.5 mg/L (range 6.6-32.0). The majority of concentrations (68.5%) were within the therapeutic range (20.0-25.0 mg/L). Adverse event rates, including drug- (5.7%) and catheter-related (5.7%) events, were low. For 32 vOPAT episodes, a clinical cure rate of 100% was observed. All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with rigorous follow-up provides safe and effective ambulatory treatment of patients with vancomycin in continuous infusion.

Fracture-related infection of the patella: Treatment options and outcome.

BACKGROUND: Fracture-related infection (FRI) after the operative management of patella fractures is a serious complication that can result in prolonged hospitalization, multiple revision procedures and permanent functional impairment. Till today, treatment modalities and outcome of FRI of the patella are not well described. Therefore, the main objective of this retrospective cohort study was to evaluate treatment options, functional outcome and healthcare costs related to FRI of the patella. METHODS: This study evaluated 111 consecutive patients that were surgically treated for patella fractures, at the department of trauma surgery of the University Hospitals Leuven (Belgium), between January 2015 and April 2020. Patients were excluded if they (1) were younger than 18 years at the time of injury or (2) died during follow up. The minimal follow-up for all patients was 18 months. RESULTS: During the 5-year study period, 107 patients with 108 patella fractures were included. A total of 10 patients were diagnosed with an FRI (9.3%). Four of these were treated with a DAIR approach and three patients underwent implant removal or exchange. Finally, three patients were treated with total patellectomy. Out of the 10 patients, two were diagnosed with a recurrence of infection. Overall, we observed substantial lower scores for all Knee Injury and Osteoarthritis Outcome Score subscales in the FRI group, compared to a reference population. Moreover, our study shows that direct hospital-related healthcare costs of FRI of the patella were nine times higher compared to non-FRI cases. CONCLUSIONS: FRI of the patella is a challenging complication and recurrence of infection not uncommon. Although multiple treatment modalities exist, a multidisciplinary patient-specific approach is crucial. An early or delayed onset infection can be managed with a DAIR approach, but only when the construct is stable and the soft tissue coverage adequate. In patients with an FRI, implant removal is preferred when the fracture has healed. A total patellectomy can be used as a salvage procedure in complex cases with acceptable functional results. Overall, FRI of the patella leads to both a negative impact on the functional status of the patient and a ninefold increase in total healthcare costs.

Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review.

According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and mortality and a rising pressure on health-care systems. However, the development of new antibiotics is an expensive and time-consuming process, urging scientists to seek alternative antimicrobial strategies. Over the past few decades, the concept of therapeutic administration of bacteriophages (also known as phages) has gained popularity worldwide. Although conceptually promising, the widespread implementation of phage therapy in routine clinical practice is restricted by the scarcity of safety and efficacy data obtained according to the strict standards of the applicable clinical trial regulations. In this systematic review, we list clinical data published between Jan 1, 2000 and Aug 14, 2021 on the safety and efficacy of phage therapy for difficult-to-treat bacterial infections, and provide an overview of trials and case studies on the use of phage therapy in several medical disciplines.

Validation of the diagnostic criteria of the consensus definition of fracture-related infection.

BACKGROUND: The recently developed fracture-related infection (FRI) consensus definition, which is based on specific diagnostic criteria, has not been fully validated in clinical studies. We aimed to determine the diagnostic performance of the criteria of the FRI consensus definition and evaluated the effect of the combination of certain suggestive and confirmatory criteria on the diagnostic performance. METHODS: A multicenter, multi-national, retrospective cohort study was performed. Patients were subdivided into an FRI or a control group, according to the treatment they received and the recommendations from a multidisciplinary team ('intention to treat'). Exclusion criteria were patients with an FRI diagnosed outside the study period, patients younger than 18 years of age, patients with pathological fractures or patients with fractures of the skull, cervical, thoracic and lumbar spine. Minimum follow up for all patients was 18 months. RESULTS: Overall, 637 patients underwent revision surgery for suspicion of FRI. Of these, 480 patients were diagnosed with FRI, treated accordingly, and included in the FRI group. The other 157 patients were included in the control group. The presence of at least one confirmatory sign was associated with a sensitivity of 97.5%, a specificity of 100% and a high discriminatory value (AUROC 0.99, p < 0.001). The presence of a clinical confirmatory criterion or, if not present, at least one positive culture was associated with the highest diagnostic performance (sensitivity: 98.6%, specificity: 100%, AUROC: 0.99 (p < 0.001)). In the subgroup of patients without clinical confirmatory signs at presentation, specificities of at least 95% were found for the clinical suggestive signs of fever, wound drainage, local warmth and redness. CONCLUSIONS: The presence of at least one confirmatory criterion identifies the vast majority of patients with an FRI and was associated with an excellent diagnostic discriminatory value. Therefore, our study validates the confirmatory criteria of the FRI consensus definition. Infection is highly likely in case of the presence of a single positive culture with a virulent pathogen. When certain clinical suggestive signs (e.g., wound drainage) are observed (individually or in combination and even without a confirmatory criterion), it is more likely than not, that an infection is present.

Isavuconazole in the Treatment of Aspergillus fumigatus Fracture-Related Infection: Case Report and Literature Review.

Aspergillus fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for Aspergillus osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. We describe a patient with Aspergillus fumigatus FRI of the tibia who was treated with isavuconazole after developing liver function disturbances during voriconazole therapy. Isavuconazole, the active moiety formed after hydrolysis of the prodrug isavuconazonium sulfate by plasma esterases, was administered in a maintenance dose of 200 mg q24 h, followed by 150 mg q24 h. The patient completed a six-month antifungal treatment course. Although fracture union was not achieved during six months of follow-up after therapy cessation, no confirmatory signs of FRI were observed. Additionally, two literature searches were conducted to review available data on antifungal treatment of Aspergillus osteomyelitis and bone penetration of antifungals. One hundred and eight cases of Aspergillus osteomyelitis, including six (5.6%) FRI cases, were identified. Voriconazole and (lipid formulations of) amphotericin B were the most commonly used antifungals. In three (2.8%) cases isavuconazole was prescribed as salvage therapy. Data on antifungal bone penetration were reported for itraconazole, voriconazole, amphotericin B, anidulafungin and 5-fluorocytosin. Isavuconazole might be a promising alternative for the treatment of Aspergillus osteomyelitis. However, standardized case documentation is needed to evaluate the efficacy of isavuconazole and other antifungals in the treatment of Aspergillus osteomyelitis, including FRI.

Comparison of the Euroimmun Borrelia 'antibody index' with Virotech immunoblot-based detection of intrathecal Borrelia antibody production for the diagnosis of Lyme neuroborreliosis.

For diagnosis of neuroborreliosis, calculation of the antibody index, based on Euroimmun Anti-Borrelia plus VlsE ELISA was compared to Virotech Borrelia Europe plus TpN17 immunoblot-based detection of Borrelia-specific intrathecal antibody production. CXCL13 results in cerebrospinal fluid were used to evaluate discordant results. A total of 64 serum/CSF pairs were analysed. Patients were classified according to European Federation of Neurological Societies criteria incorporating Virotech results. For the Euroimmun assay, a sensitivity of 100% and specificity of 94% was found. Agreement between the both tests was almost perfect (κ 0.81). Both methods are appropriate for the detection of Borrelia-specific intrathecal antibody production.

Importance of anti-SARS-CoV-2 assay antigenic composition as revealed by the results of the Belgian external quality assessment (EQA) scheme.

We report on sample IS/17575 since it generated highly divergent results in the Belgian SARS-CoV-2 serology external quality assessment scheme. Sample IS/17575 was serum originating from a 30 years old male patient. 124 diagnostic laboratories analysed this sample. A total of 168 results was returned (including 5 doubles). Overall, 38 were positive. All tests against S1 were positive except the Euroimmun IgG ELISA and the Ortho clinical Diagnostics VITROS IgG CLIA. All tests against S1/S2 (Liaison, Diasorin) resulted in a signal above cutoff. Assays against RBD, mostly generate a negative result. An exception are the Wantai SARS-CoV-2 ELISA's. All tests targeting N protein were negative. The survey shows, when >6 months post-infection, assays targeting at least S1, and preferably S1 combined with S2, are the most sensitive. This finding accentuates the necessity of external quality assessment schedules and importance of antigenic composition of serologic SARS-CoV-2 assays.

What is the diagnostic value of the Centers for Disease Control and Prevention criteria for surgical site infection in fracture-related infection?

BACKGROUND: Fracture-related infection (FRI) remains one of the most challenging complications in orthopaedic trauma surgery. An early diagnosis is of paramount importance to guide treatment. The primary aim of this study was to compare the Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of organ/space surgical site infection (SSI) to the recently developed diagnostic criteria of the FRI consensus definition in operatively treated fracture patients. METHODS: This international multicenter retrospective cohort study evaluated 257 patients with 261 infections after operative fracture treatment. All patients included in this study were considered to have an FRI and treated accordingly ('intention to treat'). The minimum follow-up was one year. Infections were scored according to the CDC criteria for organ/space SSI and the diagnostic criteria of the FRI consensus definition. RESULTS: Overall, 130 (49.8%) FRIs were captured when applying the CDC criteria for organ/space SSI, whereas 258 (98.9%) FRIs were captured when applying the FRI consensus criteria. Patients could not be classified as having an infection according to the CDC criteria mainly due to a lack of symptoms within 90 days after the surgical procedure (n = 96; 36.8%) and due to the fact that the surgery was performed at an anatomical localization not listed in the National Healthcare Safety Network (NHSN) operative procedure code mapping (n = 37; 14.2%). CONCLUSION: This study confirms the importance of standardization with respect to the diagnosis of FRI. The results endorse the recently developed FRI consensus definition. When applying these diagnostic criteria, 98.9% of the infections that occured after operative fracture treatment could be captured. The CDC criteria for organ/space SSI captured less than half of the patients with an FRI requiring treatment, and seemed to have less diagnostic value in this patient population.