The Role of Nuclear Medicine Imaging with 18F-FDG PET/CT, Combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT in the Evaluation of Patients with Chronic Problems after TKA or THA in a Prospective Study.

BACKGROUND: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with 18F-FDG PET/CT (FDG PET/CT), combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm. MATERIALS AND METHODS: Fifty-five patients underwent imaging with 99mTc-HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up. RESULTS: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74-1.00), a specificity of 97% (CI 0.82-1.00), and an accuracy of 98% (CI 0.88-1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74-1.00), 71% (CI 0.56-0.90), and 79% (CI 0.68-0.93), respectively. CONCLUSIONS: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.

Multidisciplinary Diagnostic Algorithm for Evaluation of Patients Presenting with a Prosthetic Problem in the Hip or Knee: A Prospective Study.

The predominant indications for revision surgery after total hip (THA) or knee arthroplasty (TKA) are an aseptic failure (AF) and prosthetic joint infection (PJI). Accurate diagnosis is crucial. Therefore, we evaluated prospectively a multidisciplinary diagnostic algorithm including multi-modal radionucleid imaging (RNI) and extended microbiological diagnostics. If the surgeon suspected PJI or AF, revision surgery was performed with multiple samples obtained in parallel for special culture procedures and later molecular analyses. Alternatively, if the underlying cause was not evident, RNI was scheduled comprising 99Tc - HDP SPECT/CT, 111In-labeled white blood cells combined with 99Tc-nanocoll bone marrow SPECT/CT, and 18F-FDG PET/CT. A multidisciplinary clinical team made a recommendation on the indication for a diagnostic procedure guided by RNI images or revision surgery. A total of 156 patients with 163 arthroplasties were included. Fifty-five patients underwent RNI. In all, 118 revision surgeries were performed in 112 patients: 71 on the indication of AF and 41 revision of PJI. Thirty-four patients were concluded with chronic pain, and revision surgery refrained. The effective median follow-up period was 13 months. A structured approach offered by the algorithm was useful for the clinician in the evaluation of patients with a failing TKA or THA. Surgical revision was possibly obviated in approximately 20% of patients where an explanation or cause of failure was not found. The algorithm served as an effective tool.

Differential Contributions of Specimen Types, Culturing, and 16S rRNA Sequencing in Diagnosis of Prosthetic Joint Infections.

Prosthetic joint failure is mainly caused by infection, aseptic failure (AF), and mechanical problems. Infection detection has been improved with modified culture methods and molecular diagnostics. However, comparisons between modified and conventional microbiology methods are difficult due to variations in specimen sampling. In this prospective, multidisciplinary study of hip or knee prosthetic failures, we assessed the contributions of different specimen types, extended culture incubations, and 16S rRNA sequencing for diagnosing prosthetic joint infections (PJI). Project specimens included joint fluid (JF), bone biopsy specimens (BB), soft-tissue biopsy specimens (STB), and swabs (SW) from the prosthesis, collected in situ, and sonication fluid collected from prosthetic components (PC). Specimens were cultured for 6 (conventional) or 14 days, and 16S rRNA sequencing was performed at study completion. Of the 156 patients enrolled, 111 underwent 114 surgical revisions (cases) due to indications of either PJI (n = 43) or AF (n = 71). Conventional tissue biopsy cultures confirmed PJI in 28/43 (65%) cases and refuted AF in 3/71 (4%) cases; one case was not evaluable. Based on these results, minor diagnostic adjustments were made. Fourteen-day cultures of JF, STB, and PC specimens confirmed PJI in 39/42 (93%) cases, and 16S rRNA sequencing confirmed PJI in 33/42 (83%) cases. One PJI case was confirmed with 16S rRNA sequencing alone and five with cultures of project specimens alone. These findings indicated that JF, STB, and PC specimen cultures qualified as an optimal diagnostic set. The contribution of sequencing to diagnosis of PJI may depend on patient selection; this hypothesis requires further investigation.

Microbiological diagnosis of device-related biofilm infections.

Medical device-related infections cause undue patient distress, increased morbidity and mortality and pose a huge financial burden on healthcare services. The pathogens are frequently distributed heterogeneously in biofilms, which can persist without being effectively cleared by host immune defenses and antibiotic therapy. At present, there is no 'gold standard' available to reveal the presence of device-related biofilm infections. However, adequate sample collection and logistics, standardised diagnostic methods, and interpretation of results by experienced personnel are important steps in efficient diagnosis and treatment of these infections. The focus of this mini review is on prosthethic joint and cardiovascular implantable device infections, which exemplify permanent devices that are placed in a sterile body site. These device-related infections represent some of the most challenging in terms of both diagnosis and treatment.

In vivo gene expression in a Staphylococcus aureus prosthetic joint infection characterized by RNA sequencing and metabolomics: a pilot study.

BACKGROUND: Staphylococcus aureus gene expression has been sparsely studied in deep-sited infections in humans. Here, we characterized the staphylococcal transcriptome in vivo and the joint fluid metabolome in a prosthetic joint infection with an acute presentation using deep RNA sequencing and nuclear magnetic resonance spectroscopy, respectively. We compared our findings with the genome, transcriptome and metabolome of the S. aureus joint fluid isolate grown in vitro. RESULT: From the transcriptome analysis we found increased expression of siderophore synthesis genes and multiple known virulence genes. The regulatory pattern of catabolic pathway genes indicated that the bacterial infection was sustained on amino acids, glycans and nucleosides. Upregulation of fermentation genes and the presence of ethanol in joint fluid indicated severe oxygen limitation in vivo. CONCLUSION: This single case study highlights the capacity of combined transcriptome and metabolome analyses for elucidating the pathogenesis of prosthetic infections of major clinical importance.

'All in a box' a concept for optimizing microbiological diagnostic sampling in prosthetic joint infections.

BACKGROUND: Accurate microbial diagnosis is crucial for effective management of prosthetic joint infections. Culturing of multiple intraoperative tissue samples has increased diagnostic accuracy, but new preparatory techniques and molecular methods hold promise of further improvement. The increased complexity of sampling is, however, a tough challenge for surgeons and assistants in the operation theatre, and therefore we devised and tested a new concept of pre-packed boxes with a complete assortment of swabs, vials and additional tools needed in the operating theatre for non-standard samples during a clinical study of prosthetic joint infections. FINDINGS: The protocol for the clinical study required triplicate samples of joint fluid, periprosthetic tissue, bone tissue, and swabs from the surface of the prosthesis. Separate boxes were prepared for percutaneous joint puncture and surgical revision; the latter included containers for prosthetic components or the entire prosthesis. During a 2-year project period 164 boxes were used by the surgeons, 98 of which contained a complete set of samples. In all, 1508 (89%) of 1685 scheduled samples were received. CONCLUSION: With this concept a high level of completeness of sample sets was achieved and thus secured a valid basis for evaluation of new diagnostics. Although enthusiasm for the project may have been a contributing factor, the extended project period suggests that the 'All in a box' concept is equally applicable in routine clinical settings with standardized but complex diagnostic sampling.

Optimizing culture methods for diagnosis of prosthetic joint infections: a summary of modifications and improvements reported since 1995.

Improving diagnosis of prosthetic joint infections (PJIs) has become an increasing challenge due to a steadily rising number of patients with prosthetic implants. Based on a systematic literature search we have ascertained the evidence base for improvement of culture diagnosis. We searched PubMed/MEDLINE using the medical subject heading (MeSH) 'prosthesis-related infections' 1995 through 2010 without further restrictions. An analogous search was conducted for ISI Web of Knowledge. A total of 1409 reports were screened for original results, obtained by methods described in sufficient detail to make replication possible. We gave priority to methods for sample preparation, culture media, culture methods and incubation time. Clinical sensitivity and specificity were calculated where possible. We found evidence to support superiority of cultures obtained from the diluent after sonication of prosthetic implants in comparison with culturing tissue biopsies. Sonication parameters and accessory steps have been studied extensively, and thresholds for significant growth have been defined. Conversely, methods for processing of soft tissue biopsies have been studied to a limited extent. Culture of synovial fluid in blood culture vials has been shown to be more sensitive (90-92 %) than intraoperative swab cultures (68-76 %) and tissue cultures (77-82 %). Formal evaluation of agar media for culturing PJI specimens seemed to be lacking. The polymicrobial nature of PJIs supports the routine use of an assortment of media suitable for recovery of fastidious, slow-growing, anaerobic and sublethally damaged bacteria. A number of studies supported an incubation period for up to 14 days. Although we identified evidence-based improvements of culture methods, there is a need for more studies especially with regard to tissue biopsies. Culturing remains an important means to identify and characterize pathogenic micro-organisms and supplements the increasing number of culture-independent assays.