Dataset Information

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms.

ABSTRACT: With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilm is crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better outcomes. Here, using in-vivo and in-vitro implant-associated infection models, we demonstrate that methicillin-sensitive and resistant Staphylococcus aureus (MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA and the models could capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can guide clinical dosing to effectively prevent or treat PJI.

SUBMITTER: Sekar A

PROVIDER: S-EPMC11092509 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms.

Sekar Amita A Fan Yingfang Y Tierney Peyton P McCanne Madeline M Jones Parker P Malick Fawaz F Kannambadi Devika D Wannomae Keith K KK Inverardi Nicoletta N Muratoglu Orhun O Oral Ebru E

bioRxiv : the preprint server for biology 20240612

With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilm is crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better outcomes. Here, using in-vivo and in-vitro implant-associated infection models, we demonstrate that methicillin-sensitive and resistant <i>Staphylococc ...[more]

PMID: 38746179

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Project description:Controversy exists regarding the optimal treatment of periprosthetic joint infection (PJI), considering control of infection, functional results as well as quality of life. Difficulties in treatment derive from the formation of biofilms within a few days after infection. Biofilms are tolerant to systemically applied antibiotics, requiring extreme concentrations for a prolonged period. Minimum biofilm eradicating concentrations (MBEC) are only feasible by the local application of antibiotics. One established approach is the use of allograft bone as a carrier, granting a sustained release of antibiotics in very high concentrations after appropriate impregnation. The purpose of this study was to determine the rate of reinfection after a one-stage revision of infected hip or knee prostheses, using antibiotic-impregnated allograft bone as the carrier and avoiding cement. Between 1 January 2004 and 31 January 2018, 87 patients with PJI, according to MSIS, underwent a one-stage revision with antibiotic-impregnated cancellous allograft bone. An amount of 17 patients had insufficient follow-ups. There were 70 remaining patients (34 male, 36 female) with a mean follow-up of 5.6 years (range 2-15.6) and with a mean age of 68.2 years (range 31.5-86.9). An amount of 38 hips and 11 knees were implanted without any cement; and 21 knees were implanted with moderate cementing at the articular surface with stems always being uncemented. Within 2 years after surgery, 6 out of 70 patients (8.6%, CI 2-15.1) showed reinfection and after more than 2 years, an additional 6 patients showed late-onset infection. Within 2 years after surgery, 11 out of 70 patients (15.7%, CI 7.2-24.2) had an implant failure for any reason (including infection) and after more than 2 years, an additional 7 patients had an implant failure. Using Kaplan-Meier analysis for all 87 patients, the estimated survival for reinfection was 93.9% (CI 88.8-99.1) at 1 year, 89.9% (CI 83.2-96.6) at 2 years and 81.5% (CI 72.1-90.9) at 5 years. The estimated survival for implant failure for any reason was 90.4% (CI 84.1-96.7) at 1 year, 80.9% (CI 72.2-89.7) at 2 years and 71.1% (CI 60.3-81.8) at 5 years. One-stage revision with antibiotic-impregnated cancellous allograft bone grants comparable results regarding infection control as with multiple stages, while shortening rehabilitation, improving quality of life for the patients and reducing costs for the health care system.

Project description:Next-generation sequencing (NGS) has developed rapidly in the last decade and is emerging as a promising diagnostic tool for periprosthetic joint infection (PJI). However, its diagnostic value for PJI is still uncertain. This systematic review aimed to explore the diagnostic value of NGS for PJI and verify its accuracy for culture-negative PJI patients. We conducted this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Medline, Embase, and Cochrane Library were searched to identify diagnostic technique studies evaluating the accuracy of NGS in the diagnosis of PJI. The diagnostic sensitivity, specificity, and positive and negative predictive values were estimated for each article. The detection rate of NGS for culture-negative PJI patients or PJI patients with antibiotic administration history was also calculated. Of the 87 identified citations, nine studies met the inclusion criteria. The diagnostic sensitivities and specificities of NGS ranged from 63% to 96% and 73% to 100%, respectively. The positive and negative predictive values ranged from 71% to 100% and 74% to 95%, respectively. The detection rate of NGS for culture-negative PJI patients in six studies was higher than 50% (range from 82% to 100%), while in three studies it was lower than 50% (range from 9% to 31%). Also, the detection rate of NGS for PJIs with antibiotic administration history ranged from 74.05% to 92.31%. In conclusion, this systematic review suggests that NGS may have the potential to be a new tool for the diagnosis of PJI and should be considered to be added to the portfolio of diagnostic procedures. Furthermore, NGS showed a favorable diagnostic accuracy for culture-negative PJI patients or PJI patients with antibiotic administration history. However, due to the small sample sizes of studies and substantial heterogeneity among the included studies, more research is needed to confirm or disprove these findings.

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

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms.

Publications

Investigating the translational value of Periprosthetic Joint Infection (PJI) models to determine the risk and severity of Staphylococcal biofilms.

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