Key aspects of soft tissue management in fracture-related infection: recommendations from an international expert group.

A judicious, well-planned bone and soft tissue debridement remains one of the cornerstones of state-of-the-art treatment of fracture-related infection (FRI). Meticulous surgical excision of all non-viable tissue can, however, lead to the creation of large soft tissue defects. The management of these defects is complex and numerous factors need to be considered when selecting the most appropriate approach. This narrative review summarizes the current evidence with respect to soft tissue management in patients diagnosed with FRI. Specifically we discuss the optimal timing for tissue closure following debridement in cases of FRI, the need for negative microbiological culture results from the surgical site as a prerequisite for definitive wound closure, the optimal type of flap in case of large soft tissue defects caused by FRI and the role of negative pressure wound therapy (NPWT) in FRI. Finally, recommendations are made with regard to soft tissue management in FRI that should be useful for clinicians in daily clinical practice.Level of evidence Level V.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Clinical Metagenomic Sequencing for Species Identification and Antimicrobial Resistance Prediction in Orthopedic Device Infection.

Diagnosis of orthopedic device-related infection is challenging, and causative pathogens may be difficult to culture. Metagenomic sequencing can diagnose infections without culture, but attempts to detect antimicrobial resistance (AMR) determinants using metagenomic data have been less successful. Human DNA depletion may maximize the amount of microbial DNA sequence data available for analysis. Human DNA depletion by saponin was tested in 115 sonication fluid samples generated following revision arthroplasty surgery, comprising 67 where pathogens were detected by culture and 48 culture-negative samples. Metagenomic sequencing was performed on the Oxford Nanopore Technologies GridION platform. Filtering thresholds for detection of true species versus contamination or taxonomic misclassification were determined. Mobile and chromosomal genetic AMR determinants were identified in Staphylococcus aureus-positive samples. Of 114 samples generating sequence data, species-level positive percent agreement between metagenomic sequencing and culture was 50/65 (77%; 95% confidence interval [CI], 65 to 86%) and negative percent agreement was 103/114 (90%; 95% CI, 83 to 95%). Saponin treatment reduced the proportion of human bases sequenced in comparison to 5-µm filtration from a median (interquartile range [IQR]) of 98.1% (87.0% to 99.9%) to 11.9% (0.4% to 67.0%), improving reference genome coverage at a 10-fold depth from 18.7% (0.30% to 85.7%) to 84.3% (12.9% to 93.8%). Metagenomic sequencing predicted 13/15 (87%) resistant and 74/74 (100%) susceptible phenotypes where sufficient data were available for analysis. Metagenomic nanopore sequencing coupled with human DNA depletion has the potential to detect AMR in addition to species detection in orthopedic device-related infection. Further work is required to develop pathogen-agnostic human DNA depletion methods, improving AMR determinant detection and allowing its application to other infection types.

General treatment principles for fracture-related infection: recommendations from an international expert group.

Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients' short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.Level of evidence: Level V.

Management of Post-Traumatic Osteomyelitis in the Lower Limb: Current State of the Art.

Osteomyelitis (OM) of the lower limb represents a large unmet global healthcare burden. It often arises from a contiguous focus of infection and is a recognized complication of open fractures or their surgical treatment, arthroplasty, and diabetic foot ulcers. Historically, this debilitating condition is associated with high rates of recurrence and secondary amputation. However, excellent long-term outcomes are now achieved by adopting a multidisciplinary approach with meticulous surgical debridement, skeletal and soft tissue reconstruction, and tailored antimicrobial treatment. This review focuses on the modern evidence-based management of post-traumatic OM in the lower limb from a reconstructive plastic surgery perspective, highlighting the latest developments and areas of controversy.

Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices.

BACKGROUND: Prosthetic joint infections are clinically difficult to diagnose and treat. Previously, we demonstrated metagenomic sequencing on an Illumina MiSeq replicates the findings of current gold standard microbiological diagnostic techniques. Nanopore sequencing offers advantages in speed of detection over MiSeq. Here, we report a real-time analytical pathway for Nanopore sequence data, designed for detecting bacterial composition of prosthetic joint infections but potentially useful for any microbial sequencing, and compare detection by direct-from-clinical-sample metagenomic nanopore sequencing with Illumina sequencing and standard microbiological diagnostic techniques. RESULTS: DNA was extracted from the sonication fluids of seven explanted orthopaedic devices, and additionally from two culture negative controls, and was sequenced on the Oxford Nanopore Technologies MinION platform. A specific analysis pipeline was assembled to overcome the challenges of identifying the true infecting pathogen, given high levels of host contamination and unavoidable background lab and kit contamination. The majority of DNA classified (> 90%) was host contamination and discarded. Using negative control filtering thresholds, the species identified corresponded with both routine microbiological diagnosis and MiSeq results. By analysing sequences in real time, causes of infection were robustly detected within minutes from initiation of sequencing. CONCLUSIONS: We demonstrate a novel, scalable pipeline for real-time analysis of MinION sequence data and use of this pipeline to show initial proof of concept that metagenomic MinION sequencing can provide rapid, accurate diagnosis for prosthetic joint infections. The high proportion of human DNA in prosthetic joint infection extracts prevents full genome analysis from complete coverage, and methods to reduce this could increase genome depth and allow antimicrobial resistance profiling. The nine samples sequenced in this pilot study have shown a proof of concept for sequencing and analysis that will enable us to investigate further sequencing to improve specificity and sensitivity.

Sonication versus Tissue Sampling for Diagnosis of Prosthetic Joint and Other Orthopedic Device-Related Infections.

Current guidelines recommend collection of multiple tissue samples for diagnosis of prosthetic joint infections (PJI). Sonication of explanted devices has been proposed as a potentially simpler alternative; however, reported microbiological yield varies. We evaluated sonication for diagnosis of PJI and other orthopedic device-related infections (DRI) at the Oxford Bone Infection Unit between October 2012 and August 2016. We compared the performance of paired tissue and sonication cultures against a "gold standard" of published clinical and composite clinical and microbiological definitions of infection. We analyzed explanted devices and a median of five tissue specimens from 505 procedures. Among clinically infected cases the sensitivity of tissue and sonication culture was 69% (95% confidence interval, 63 to 75) and 57% (50 to 63), respectively (P < 0.0001). Tissue culture was more sensitive than sonication for both PJI and other DRI, irrespective of the infection definition used. Tissue culture yield was higher for all subgroups except less virulent infections, among which tissue and sonication culture yield were similar. The combined sensitivity of tissue and sonication culture was 76% (70 to 81) and increased with the number of tissue specimens obtained. Tissue culture specificity was 97% (94 to 99), compared with 94% (90 to 97) for sonication (P = 0.052) and 93% (89 to 96) for the two methods combined. Tissue culture is more sensitive and may be more specific than sonication for diagnosis of orthopedic DRI in our setting. Variable methodology and case mix may explain reported differences between centers in the relative yield of tissue and sonication culture. Culture yield was highest for both methods combined.

Molecular Diagnosis of Orthopedic-Device-Related Infection Directly from Sonication Fluid by Metagenomic Sequencing.

Culture of multiple periprosthetic tissue samples is the current gold standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through culture of sonication fluid from explants. However, current techniques can have relatively low sensitivity, with prior antimicrobial therapy and infection by fastidious organisms influencing results. We assessed if metagenomic sequencing of total DNA extracts obtained direct from sonication fluid can provide an alternative rapid and sensitive tool for diagnosis of PJI. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopedic device infections. Reads from Illumina MiSeq sequencing were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples. Compared to results from sonication fluid culture, the species-level sensitivity of metagenomic sequencing was 61/69 (88%; 95% confidence interval [CI], 77 to 94%; for derivation samples 35/38 [92%; 95% CI, 79 to 98%]; for validation samples, 26/31 [84%; 95% CI, 66 to 95%]), and genus-level sensitivity was 64/69 (93%; 95% CI, 84 to 98%). Species-level specificity, adjusting for plausible fastidious causes of infection, species found in concurrently obtained tissue samples, and prior antibiotics, was 85/97 (88%; 95% CI, 79 to 93%; for derivation samples, 43/50 [86%; 95% CI, 73 to 94%]; for validation samples, 42/47 [89%; 95% CI, 77 to 96%]). High levels of human DNA contamination were seen despite the use of laboratory methods to remove it. Rigorous laboratory good practice was required to minimize bacterial DNA contamination. We demonstrate that metagenomic sequencing can provide accurate diagnostic information in PJI. Our findings, combined with the increasing availability of portable, random-access sequencing technology, offer the potential to translate metagenomic sequencing into a rapid diagnostic tool in PJI.

Three to six tissue specimens for histopathological analysis are most accurate for diagnosing periprosthetic joint infection.

AIMS: The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). METHODS: In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. RESULTS: Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). CONCLUSION: Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue.Cite this article: Bone Joint J 2023;105-B(2):158-165.

A Survey of Orthopedic Surgical Management of Pressure Ulcer-Related Pelvic Osteomyelitis.

Pressure-ulcer related pelvic osteomyelitis is managed with little high-quality evidence. We undertook an international survey of orthopedic surgical management, covering diagnostic parameters, multidisciplinary input, and surgical approaches (indications, timing, wound closure, and adjunctive therapies). This identified areas of consensus and disagreement, representing a starting point for future discussion and research.

The Sinus Tract in Bone and Joint Infection: Minimally Invasive Salvation or Prolonged Suffering? A Multicenter Study.

This study assessed the quality of life (QOL) and the functional outcome in daily living in patients with a chronic, treatment-resistant periprosthetic joint infection (PJI) or osteomyelitis, living with a natural or iatrogenic sinus tract. METHODS: A follow-up examination in three national reference centers for septic bone and joint surgery was performed utilizing the Hospital Anxiety and Depression Scale (HADS-D/A), the Visual Analogue Scale (VAS), and the Short Form-36 (SF-36) score, including patients with a chronic sinus tract due to treatment-resistant PJI or osteomyelitis. RESULTS: In total, 48 patients were included, with a mean follow-up time of 43.1 ± 23.9 months. The mean SF-36 Mental Component Summary (MCS) was 50.2 (±12.3) and the Physical Component Summary (PCS) was 33.9 (±11.3). The mean HADS-D was 6.6 (±4.4) and HADS-A was 6.2 (±4.6), and the VAS was 3.4 (±2.6). The SF-36 MCS showed no significant differences between the study group and the standard population (47.0, p = 0.10), as well as the HADS-A. The PCS in the study population was significantly worse (50.0, p < 0.001), as was the HADS-D. CONCLUSIONS: A sinus tract represents a treatment option in selected cases with an acceptable QOL. The treatment should be considered for multimorbid patients with a high perioperative risk or if the bone or soft tissue quality prevents surgery.

The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study).

AIM: This study investigated the compliance with a guideline-based antibiotic regimen on the outcome of patients surgically treated for a fracture-related infection (FRI). METHOD: In this international multicenter observational study, patients were included when diagnosed with an FRI between 2015 and 2019. FRI was defined according to the FRI consensus definition. All patients were followed for at least one year. The chosen antibiotic regimens were compared to the published guidelines from the FRI Consensus Group and correlated to outcome. Treatment success was defined as the eradication of infection with limb preservation. RESULTS: A total of 433 patients (mean age 49.7 ± 16.1 years) with FRIs of mostly the tibia (50.6%) and femur (21.7%) were included. Full compliance of the antibiotic regime to the published guidelines was observed in 107 (24.7%) cases. Non-compliance was mostly due to deviations from the recommended dosing, followed by the administration of an alternative antibiotic than the one recommended or an incorrect use or non-use of rifampin. Non-compliance was not associated with a worse outcome: treatment failure was 12.1% in compliant versus 13.2% in non-compliant cases (p = 0.87). CONCLUSIONS: We report good outcomes in the treatment of FRI and demonstrated that minor deviations from the FRI guideline are not associated with poorer outcomes.

Diagnosing periprosthetic joint infections : a comparison of infection definitions: EBJIS 2021, ICM 2018, and IDSA 2013.

AIMS: This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI). METHODS: In this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient. RESULTS: Of 206 included patients, 101 (49%) were diagnosed with PJI with the EBJIS definition. IDSA and ICM diagnosed 99 (48%) and 86 (42%) as infected, respectively. A total of 84 cases (41%) had an infection based on all three criteria. In 15 cases (n = 15/206; 7%), PJI was present when applying only the IDSA and EBJIS criteria. No infection was detected by one definition alone. Inconclusive diagnoses occurred more frequently with the ICM criteria (n = 30/206; 15%) compared to EBJIS (likely infections: n = 16/206; 8%) (p = 0.029). A better preoperative performance of the EBJIS definition was seen compared with the ICM and IDSA definitions (p < 0.001). CONCLUSION: The novel EBJIS definition identified all PJIs diagnosed by any other criteria. Use of the EBJIS definition significantly reduced the number of uncertain diagnoses, allowing easier clinical decision-making.Cite this article: Bone Joint Res 2022;11(9):608-618.

Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier.

AIMS: Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. METHODS: A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). RESULTS: At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). CONCLUSION: We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion.Cite this article: Bone Joint J 2022;104-B(9):1095-1100.

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.

Does the Use of Local Antibiotics Affect Clinical Outcome of Patients with Fracture-Related Infection?

This international, multi-center study evaluated the effect of antibiotic-loaded carriers (ALCs) on outcome in patients with a fracture-related infection (FRI) and evaluated whether bacterial resistance to the implanted antibiotics influences their efficacy. All patients who were retrospectively diagnosed with FRI according to the FRI consensus definition, between January 2015 and December 2019, and who underwent surgical treatment for FRI at any time point after injury, were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse probability for treatment weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of ALCs and recurrence rate of FRI at 12 months and 24 months. Overall, 429 patients with 433 FRIs were included. A total of 251 (58.0%) cases were treated with ALCs. Gentamicin was the most frequently used antibiotic (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received ALCs and in 34/182 (18.7%) patients who did not (unadjusted hazard ratio (uHR): 0.48, 95% CI: [0.29-0.81]). Resistance of cultured microorganisms to the implanted antibiotic was not associated with a higher risk of recurrence of FRI (uHR: 0.75, 95% CI: [0.32-1.74]). The application of ALCs in treatment of FRI is likely to reduce the risk of recurrence of infection. The high antibiotic concentrations of ALCs eradicate most pathogens regardless of susceptibility test results.

Systematic review of risk prediction studies in bone and joint infection: are modifiable prognostic factors useful in predicting recurrence?

Background: Classification systems for orthopaedic infection include patient health status, but there is no consensus about which comorbidities affect prognosis. Modifiable factors including substance use, glycaemic control, malnutrition and obesity may predict post-operative recovery from infection. Aim: This systematic review aimed (1) to critically appraise clinical prediction models for individual prognosis following surgical treatment for orthopaedic infection where an implant is not retained; (2) to understand the usefulness of modifiable prognostic factors for predicting treatment success. Methods: EMBASE and MEDLINE databases were searched for clinical prediction and prognostic studies in adults with orthopaedic infections. Infection recurrence or re-infection after at least 6 months was the primary outcome. The estimated odds ratios for the primary outcome in participants with modifiable prognostic factors were extracted and the direction of the effect reported. Results: Thirty-five retrospective prognostic cohort studies of 92 693 patients were included, of which two reported clinical prediction models. No studies were at low risk of bias, and no externally validated prediction models were identified. Most focused on prosthetic joint infection. A positive association was reported between body mass index and infection recurrence in 19 of 22 studies, similarly in 8 of 14 studies reporting smoking history and 3 of 4 studies reporting alcohol intake. Glycaemic control and malnutrition were rarely considered. Conclusion: Modifiable aspects of patient health appear to predict outcomes after surgery for orthopaedic infection. There is a need to understand which factors may have a causal effect. Development and validation of clinical prediction models that include participant health status will facilitate treatment decisions for orthopaedic infections.

Diagnostic accuracy of neutrophil counts in histopathological tissue analysis in periprosthetic joint infection using the ICM, IDSA, and EBJIS criteria.

AIMS: Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. METHODS: A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. RESULTS: Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). CONCLUSION: With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536-547.

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.