Fracture-related infection (FRI) is a severe complication after bone injury and can pose a serious diagnostic challenge. Overall, there is a limited amount of scientific evidence regarding diagnostic ...criteria for FRI. For this reason, the AO Foundation and the European Bone and Joint Infection Society proposed a consensus definition for FRI to standardize the diagnostic criteria and improve the quality of patient care and applicability of future studies regarding this condition. The aim of this article was to summarize the available evidence and provide recommendations for the diagnosis of FRI. For this purpose, the FRI consensus definition will be discussed together with a proposal for an update based on the available evidence relating to the diagnostic value of clinical parameters, serum inflammatory markers, imaging modalities, tissue and sonication fluid sampling, molecular biology techniques, and histopathological examination. Second, recommendations on microbiology specimen sampling and laboratory operating procedures relevant to FRI will be provided.
LEVEL OF EVIDENCE:Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Fracture-related infection (FRI) remains a challenging complication that imposes a heavy burden on orthopaedic trauma patients. The surgical management eradicates the local infectious focus and if ...necessary facilitates bone healing. Treatment success is associated with debridement of all dead and poorly vascularized tissue. However, debridement is often associated with the formation of a dead space, which provides an ideal environment for bacteria and is a potential site for recurrent infection. Dead space management is therefore of critical importance. For this reason, the use of locally delivered antimicrobials has gained attention not only for local antimicrobial activity but also for dead space management. Local antimicrobial therapy has been widely studied in periprosthetic joint infection, without addressing the specific problems of FRI. Furthermore, the literature presents a wide array of methods and guidelines with respect to the use of local antimicrobials. The present review describes the scientific evidence related to dead space management with a focus on the currently available local antimicrobial strategies in the management of FRI.
LEVEL OF EVIDENCE:Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
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.
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.
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.
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.
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.
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).
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).
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:
2022;104-B(9):1095-1100.
Fracture-related infection (FRI) is a major complication in musculoskeletal trauma and one of the leading causes of morbidity. Standardization of general treatment strategies for FRI has been poor. ...One of the reasons is the heterogeneity in this patient population, including various anatomical locations, multiple fracture patterns, different degrees of soft-tissue injury, and different patient conditions. This variability makes treatment complex and hard to standardize. As these infections are biofilm-related, surgery remains the cornerstone of treatment, and this entails multiple key aspects (eg, fracture fixation, tissue sampling, debridement, and soft-tissue management). Another important aspect, which is sometimes less familiar to the orthopaedic trauma surgeon, is systemic antimicrobial therapy. The aim of this article is to summarize the available evidence and provide recommendations for systemic antimicrobial therapy with respect to FRI, based on the most recent literature combined with expert opinion.
LEVEL OF EVIDENCE:Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using ...the fracture-related infection (FRI) consensus definition.
A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree.
Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10
/l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases.
The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article:
2020;102-B(7):904-911.
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).
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.
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).
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:
2023;105-B(2):158-165.
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.
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