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Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

ABSTRACT: No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et al., Histopathology 54:847-853, 2009. https://doi.org/10.1111/j.1365-2559.2009.03313.x). We performed a multicenter prospective study, which compared both methods for the diagnosis of PJI. All suspicions of PJI (n = 264) between December 2010 and March 2012 in seven centers were prospectively included. Five perioperative specimens were collected per patient for cultures, and one was collected for histology. Diagnosis of PJI was made according to the Infectious Diseases Society of America (IDSA) guidelines. Histopathological analysis classified the patients according to the threshold of 23 neutrophils and according to the classification of Morawietz. Performances of both methods were compared by using clinical and/or bacteriological criteria as the gold standard. Among 264 patients with suspected PJI, a diagnosis of infection was confirmed in 215 and unconfirmed in 49 patients. Histopathological analysis was available for 150 confirmed PJI and 40 unconfirmed PJI cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.7%, 90.0%, 96.7%, 52.9%, and 81.1%, respectively, for the Morawietz classification, and 82.0%, 90.0%, 96.9%, 57.1%, and 83.7%, respectively, for the 23-neutrophil threshold. The new algorithm using a threshold of 23 neutrophils can be proposed as a new gold standard for the histopathological diagnosis of PJI.

SUBMITTER: Bemer P

PROVIDER: S-EPMC6113493 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

Bémer Pascale P Léger Julie J Milin Serge S Plouzeau Chloé C Valentin Anne Sophie AS Stock Nathalie N Jolivet-Gougeon Anne A Moreau Anne A Corvec Stéphane S Quintin-Roue Isabelle I Tandé Didier D Héry-Arnaud Geneviève G Rousselet Marie-Christine MC Lemarié Carole C Kempf Marie M Michenet Patrick P Bret Laurent L de Pinieux Gonzague G Burucoa Christophe C

Journal of clinical microbiology 20180827 9

No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et a ...[more]

PMID: 29976593

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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:UNLABELLED:Despite known low sensitivity, culture of periprosthetic tissue specimens on agars and in broths is routine. Culture of periprosthetic tissue samples in blood culture bottles (BCBs) is potentially more convenient, but it has been evaluated in a limited way and has not been widely adopted. The aim of this study was to compare the sensitivity and specificity of inoculation of periprosthetic tissue specimens into blood culture bottles with standard agar and thioglycolate broth culture, applying Bayesian latent class modeling (LCM) in addition to applying the Infectious Diseases Society of America (IDSA) criteria for prosthetic joint infection. This prospective cohort study was conducted over a 9-month period (August 2013 to April 2014) at the Mayo Clinic, Rochester, MN, and included all consecutive patients undergoing revision arthroplasty. Overall, 369 subjects were studied; 117 (32%) met IDSA criteria for prosthetic joint infection, and 82% had late chronic infection. Applying LCM, inoculation of tissues into BCBs was associated with a 47% improvement in sensitivity compared to the sensitivity of conventional agar and broth cultures (92.1 versus 62.6%, respectively); this magnitude of change was similar when IDSA criteria were applied (60.7 versus 44.4%, respectively; P = 0.003). The time to microorganism detection was shorter with BCBs than with standard media (P < 0.0001), with aerobic and anaerobic BCBs yielding positive results within a median of 21 and 23 h, respectively. Results of our study demonstrate that the semiautomated method of periprosthetic tissue culture in blood culture bottles is more sensitive than and as specific as agar and thioglycolate broth cultures and yields results faster. IMPORTANCE:Prosthetic joint infections are a devastating complication of arthroplasty surgery. Despite this, current microbiological techniques to detect and diagnose infections are imperfect. This study examined a new approach to diagnosing infections, through the inoculation of tissue samples from around the prosthetic joint into blood culture bottles. This study demonstrated that, compared to current laboratory practices, this new technique increased the detection of infection. These findings are important for patient care to allow timely and accurate diagnosis of infection.

Project description:BackgroundControversies still exist regarding the optimal diagnostic and therapeutic strategies in patients with prosthetic joint infections (PJI).Questions/purposesHow effective are preoperative and intraoperative cultures in isolating organisms and how do these culture results compare to one another? What are the results of surgical treatment of PJI in the hip and knee in an international, tertiary referral center cohort?Patients and methodsOne hundred sixteen patients (N = 59 hip PJI, N = 57 knee PJI) were recruited prospectively to registries at three international, tertiary referral centers between December 2008 to November 2011. Retrospective review of prospective registry data including demographics, microbiology results, and operative reports was performed.ResultsPreoperative synovial fluid aspiration yielded an organism in only 45.2% and 44.4% of cases, respectively, for knee and hip PJI. False-negative rates of preoperative aspiration relative to intraoperative culture were 56% and 46% in hip and knee PJI, respectively, with discordance rates of 25% and 21.4%, respectively. Rates of negative intraoperative cultures were 15% in hip PJI and 20.7% in knee PJI. Open debridement with prosthetic retention was the most common initial revision procedure performed (48.3% of hip PJI and 63.8% of knee PJI). This method of revision was successful in 41.3% of hip PJI and 59.4% of knee PJI. Initial failure rates for prosthetic revision was lower than debridement with prosthetic retention but remained substantial in both hip PJI (initial success of one-stage exchange 60% and two-stage exchange 70%) and knee PJI (initial success of one-stage exchange 80% and two-stage exchange 75%).ConclusionDiagnosis and treatment of PJI remains challenging with difficulty in isolating the offending organism and with high rates of prosthetic revision and initial treatment failures. Future advances in organism isolation and international standardization of treatment protocols may improve patient outcomes.

Project description:Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4), and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.

Project description:The volume of joint replacement surgery has risen steadily in recent years, because the population is aging and increasingly wishes to reserve a high functional status onward into old age. Infection is among the more common complications of joint replacement surgery, arising in 0.2% to 2% of patients, or as many as 9% in special situations such as the implantation of megaprostheses. The associated morbidity and mortality are high. It is thus very important to minimize risk factors for infection and to optimize the relevant diagnostic and therapeutic strategies.This review is based on pertinent publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations.The crucial diagnostic step is joint biopsy for the identification of the pathogenic organism, which succeeds with over 90% sensitivity and specificity. If the prosthesis is firmly anchored in bone, the pathogen is of a type that responds well to treatment, and symptomatic infection has been present only for a short time, then rapidly initiated treatment can save the prosthesis in 35-90% of cases. The pillars of treatment are thorough surgical care (radical débridement) and targeted antibiotic therapy. On the other hand, if the prosthesis is loose or the pathogen is of a poorly treatable type, the infection can generally only be cured by a change of the prosthesis. This can be performed in either one or two procedures, always in conjunction with systemic antibiotic therapy tailored to the specific sensitivity and resistance pattern of the pathogen.The risk of infection of an artificial joint is low, but the overall prevalence of such infections is significant, as the number of implanted joints is steadily rising. Artificial joint infections should be treated by a standardized algorithm oriented toward the recommendations of current guidelines. Many of these recommendations, however, are based only on expert opinion, as informative studies providing high-grade evidence are lacking. Thus, for any particular clinical situation, there may now be multiple therapeutic approaches with apparently comparable efficacy. Randomized trials are urgently needed.

Dataset Information

Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

Publications

Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

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