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Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

ABSTRACT: Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [18F]FDG and [18F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([89Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P?

SUBMITTER: Pickett JE

PROVIDER: S-EPMC5916877 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

Pickett Julie E JE Thompson John M JM Sadowska Agnieszka A Tkaczyk Christine C Sellman Bret R BR Minola Andrea A Corti Davide D Lanzavecchia Antonio A Miller Lloyd S LS Thorek Daniel Lj DL

Bone research 20180425

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging to ...[more]

PMID: 29707402

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Project description:BackgroundThere is currently no commonly accepted method of stratifying complexity of prosthetic joint infection (PJI). This study assesses a new classification, the Joint-Specific, Bone involvement, Anti-microbial options, Coverage of the soft tissues, Host status (JS-BACH) classification, for predicting clinical and patient reported outcomes in PJI.MethodsPatients who received surgery for PJI at two centres in the UK between 2010 and 2015 were classified using JS-BACH as 'uncomplicated', 'complex' or 'limited treatment options'. Patient reported outcomes were recorded at 365-days following the index operation and included the EuroQol EQ-5D-3L index score and the EQ-visual analogue score (VAS). Clinical outcome data were obtained from the most recent follow-up appointment.Findings220 patients met the inclusion criteria. At 365-days following the index operation, patients with 'uncomplicated' PJI reported similar EQ-index scores (0.730, SD:0.326) and EQ-VAS (79.4, SD:20.9) compared to the age-matched population. Scores for 'uncomplicated' PJI were significantly higher than patients classified as having 'complex' (EQ-index:0.515 SD:0.323, p = 0.012; EQ-VAS:68.4 SD:19.4, p = 0.042) and 'limited treatment options' PJI (EQ-index:0.333 SD:0.383, p < 0.001; EQ-VAS:60.2, SD:23.1, p = 0.005). The median time to final follow-up was 4.7 years (inter-quartile range 2.7-6.7 years) where there were 74 cases (33.6%) of confirmed recurrence. Using death as a competing risk, the Cox proportional-hazards ratio of recurrence for 'complex' versus 'uncomplicated' PJI was 23.7 (95% CI:3.23-174.0, p = 0.002) and having 'limited options' verses 'uncomplicated' PJI was 57.7 (95% CI:7.66-433.9, p < 0.001).InterpretationThe JS-BACH classification can help predict likelihood of recurrence and quality of life following surgery for PJI. This will aid clinicians in sharing prognostic information with patients and help guide referral for specialist management of PJI.

Project description:BackgroundIn the absence of a gold standard criterion for diagnosing prosthetic joint infections (PJI), sonication of the removed implant may provide superior microbiological identification to synovial fluid and peri-implant tissue cultures. The aim of this retrospective study was to assess the role of sonication culture compared to tissue cultures for diagnosing PJI, using different consensus and international guidelines for PJI definition.MethodsData of 146 patients undergoing removal of hip or knee arthroplasties between 2010 and 2018 were retrospectively reviewed. The International Consensus Meeting (ICM-2018), Musculoskeletal Infection Society (MSIS), Infectious Diseases Society of America (IDSA), the European Bone and Joint Infection Society (EBJIS), and a modified clinical criterion, were used to compare the performance of microbiological tests. McNemar´s test and proportion comparison were employed to calculate p-value.ResultsOverall, 56% (82/146) were diagnosed with PJI using the clinical criteria. Out of these cases, 57% (47/82) tested positive on tissue culture and 93% (76/82) on sonication culture. Applying this clinical criterion, the sensitivity of sonication fluid and tissue cultures was 92.7% (95% CI: 87.1%- 98.3%) and 57.3% (95% CI: 46.6%-68.0%) (p<0.001), respectively. When both methods were combined for diagnosis (sonication and tissue cultures) sensitivity reached 96.3% (95% CI: 91.5%-100%). Sonication culture and the combination of sonication with tissue cultures, showed higher sensitivity rates than tissue cultures alone for all diagnostic criteria (ICM-18, MSIS, IDSA and EBJIS) applied. Conversely, tissue culture provided greater specificity than sonication culture for all the criteria assessed, except for the EBJIS criteria, in which sonication and tissue cultures specificity was 100% and 95.3% (95% CI: 87.8-100%), respectively (p = 0.024).ConclusionsIn a context where diagnostic criteria available have shortcomings and tissue cultures remain the gold standard, sonication cultures can aid PJI diagnosis, especially when diagnostic criteria are inconclusive due to some important missing data (joint puncture, histology).

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Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

Publications

Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone.

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