Prosthetic Joint Infection Patients Research Articles

Phage therapy in prosthetic joint infections caused by Staphylococcus aureus - A literature review.

Prosthetic joint infections (PJIs) are dreaded arthroplasty complications often caused by Staphylococcus aureus. Due to methicillin-resistant S. aureus (MRSA) strains or biofilm formation, successful treatment remains difficult. Currently, two-stage revision surgery constitutes the gold standard therapy of PJIs, sometimes replaced or supplemented by debridement, antibiotics, and implant retention (DAIR). Given the dire consequences of therapeutic failure, bacteriophage therapy might be another treatment option. Here we provide a comprehensive literature review addressing theefficacy of phages applied against S.aureus as causative agent of PJIs. The included 17 publications had in common that the applied phages proved to be effective against various S. aureus isolates including MRSA even in biofilms. Experiments with mice, rats, rabbits, and moth larvaeconfirmed favorable features of phage preparations in PJI treatment in vivo; including its synergistic with antibiotics. Case reports of PJI patients unanimously described the bacterial eradication following, alongside other measures, intravenous and intra-articular phage administration. Generally, no major side effects occurred, but in some cases elevated liver transaminases were observed. To conclude, our review compiled promising evidence suggesting the safety and suitability of phage therapy as an adjuvant to DAIR in S. aureus PJIs, and thus, underscores the significance of further research.

16S rRNA sequencing reveals microbiota differences in orthopedic implants between aseptic loosening and prosthetic joint infection cases.

Prosthetic joint infection (PJI) and aseptic loosening (AL) are common complications of total joint arthroplasty. An accumulation of evidence indicates the presence of microbial communities on prosthetic implants, but the overall microbial profile is unclear. In this study, we aimed to investigate the differences in the microbial composition of prosthetic implants obtained from PJI and AL patients using the 16S rRNA sequencing method. Patients who underwent revision hip, knee, or shoulder arthroplasty caused by PJI (n = 20) or AL (n = 10) were enrolled in the study. 16S rRNA sequencing targeting the V3-V4 region was performed on the microbial specimens collected from synovial fluid, periprosthetic deep-tissue, and biofilm during the revision surgery. The sequenced raw data were analysed for microbial composition and ecological and differential abundance analyses using bioinformatics tools. The AL group had relatively balanced and higher diversity, with Staphylococcus, Streptococcus, and Veillonella being prominent. In the PJI group, Staphylococcus and Pseudomonas were predominant, especially in deep-tissue samples and biofilm samples, respectively. The differential abundance analysis identified 15 and 2 distinctive taxa in the AL and PJI groups, respectively. Our findings provided preliminary insights supporting the existence of periprosthetic microbiota in orthopedic implants and explaining the differences in microbial composition between the AL and PJI groups.

Does retained cement or hardware during 2-stage revision shoulder arthroplasty for infection increase the risk of recurrent infection?

IntroductionWhen treating chronic prosthetic joint infection (PJI) after shoulder arthroplasty, removal of the implants and cement is typically pursued because they represent a potential nidus for infection. However, complete removal can increase morbidity and compromise bone stock that is important for achieving stable revision implants. The purpose of this study is to compare the rates of repeat infection after 2-stage revision for PJI in patients who have retained cement or hardware compared to those who had complete removal. Material and MethodsWe retrospectively analyzed all two-stage revision total shoulder arthroplasties (TSAs) performed for infection at two institutions between 2011 and 2020 with minimum two-year follow-up from completion of the two-stage revision. Patients were included if they met the International Consensus Meeting (ICM) criteria for probable or definite infection2. Postoperative radiographs after the first-stage of the revision consisting of prosthesis and cement removal and placement of an antibiotic spacer were reviewed to evaluate for retained cement or hardware. Repeat infection was defined as either ≥2 positive cultures at the time of second-stage revision with the same organism cultured during the first-stage revision or repeat surgery for infection after the two-stage revision in patients that again met the ICM criteria for probable or definite infection. The rate of repeat infection among patients with retained cement or hardware was compared to the rate of infection among patients without retained cement or hardware. ResultsThirty-seven patients met inclusion criteria and were included in the analysis. Six (16%) patients had retained cement and one patient (3%) had two retained broken glenoid baseplate screws after first-stage revision. Of the ten cases of recurrent infection, one case (10%) involved retained cement/hardware. Age at revision (60.9±10.6 vs. 65.0±9.6, p=0.264), BMI (33.4±7.2 vs. 29.7±7.3, p=0.184), Charlson Comorbidity Index (2 (0-8) vs. 3 (0-6), p=0.289), male sex (7 vs. 16, p=0.420) and presence of diabetes (1 vs. 3, p=0.709) were not associated with repeat infection. Retained cement or hardware was also not associated with a repeat risk of infection (1 vs. 6, OR=0.389, p=0.374). DiscussionWe did not find an increased risk of repeat infection in patients with retained cement or hardware compared to those without. Therefore, we believe that surgeons should consider leaving cement or hardware that is difficult to remove and may lead to increased morbidity and future complications.

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis/HIF1a axis.

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. In addition, single-cell RNA-Seq (scRNA-Seq) analysis of granulocytes from PJI patients also showed an enrichment in glycolysis and hypoxia-response genes. These findings support the importance of a glycolysis/HIF1a axis in promoting G-MDSC antiinflammatory activity and biofilm persistence during PJI.

A “Dry Tap” in Prosthetic Joint Infection Workup of Total Hip Arthroplasty Is Not Reassuring

BackgroundSynovial fluid analysis is important in diagnosing prosthetic joint infection (PJI). The rate of culture-positive PJI in patients who have a dry tap of a total hip arthroplasty (THA) is not well described. MethodsWe reviewed all image-guided THA aspirations, performed from 2014 to 2021 at a single academic institution. Aspirations were categorized as successful (≥ 0.5 mL) or unsuccessful (< 0.5 mL, “dry tap”). We analyzed culture data on all repeat aspirations and revision surgeries performed within 90 days of the initial dry tap. ResultsWe reviewed 275 consecutive attempted THA aspirations of which 100 (36.4%) resulted in a dry tap. The dry tap cohort had a significantly higher percentage of fluoroscopic-guided aspirations (64%) and fewer ultrasound-guided aspirations (36%) compared to the successful aspiration cohort (48.9% fluoroscopic, 53.1% ultrasound, P = .0061). Of the 100 patients who have dry taps, 48 underwent revision surgery within 90 days of the initial dry tap, and 15 resulted in 2 or more positive cultures. The rate of PJI defined by MusculoSkeletal Infection Society major criteria in the dry tap cohort was 16.0%. ConclusionsAttempted aspiration of a THA resulted in a dry tap 36.4% of the time. Of those patients who had a dry tap, 16.0% were subsequently found to have PJI based on MusculoSkeletal Infection Society major criteria. Therefore, a “dry tap” does not exclude the diagnosis of infection and should not be considered reassuring for the absence of PJI.

1297. Implementation of a Prosthetic Joint Infection Clinic in a Rural Setting

Abstract Background Nearly one million patients undergo hip or knee replacements in the United States every year This number is expected to double by 2030. The rate of prosthetic joint infection (PJI) ranges from 0.5 to 2% which translates to between 50,000 to 200,000 PJIs annually. Prosthetic joint infections have high rates of morbidity and mortality. These complex patients are best managed in a multidisciplinary clinic. In 2018, we implemented a specialized Ortho ID clinic where PJI patients are seen by their joint surgeon and ID physician in a single coordinated visit. In this study, we compared no-show rate, miles traveled to clinic, C diff rates, and other complication rates for PJI patients before and after the implementation of our Ortho ID clinic. Methods We performed a chart review of PJI patients treated at our institution, comparing a group of patients who were treated prior 2018 in the General ID clinic to a group of patients who were treated after 2018 in the Ortho ID clinic. We assessed no-show rates, cumulative distance driven and time spent driving (calculated using Google Maps), C. diff rate, and rates of side effects between the 2 groups. Results The combination clinic improved ID follow-up. Prior to the clinic, only 70% of PJI patients were followed by ID after hospital discharge compared to 100% after the clinic was founded. The no-show rate for PJI patients decreased from 18.2% pre-clinic to 6.9% post-clinic. The mean distance traveled pre-clinic was 226 miles compared to 192 miles post-clinic. The C diff rate decreased from 9.09% pre-clinic to 5.22% post-clinic. Rate of acute kidney injury decreased from 11.1% pre-clinic to 3.45% post-clinic. Conclusion Our Ortho ID Clinic’s biggest impact was improving ID follow-up for these complicated patients. Prior to the Clinic’s implementation, approximately 30% of PJI patients never followed up with ID after being discharged from the hospital. We saw positive outcomes with regards to reducing C diff rates and rates of acute kidney injury. Disclosures All Authors: No reported disclosures

A Pilot Study Using a Standardized Method of Measuring Distress Demonstrates Higher Levels in Septic Revisions

BackgroundCombined Orthopaedic Infectious Disease Clinics facilitate care for prosthetic joint infection (PJI) patients similar to multidisciplinary care in cancer centers. The National Comprehensive Cancer Network developed a standardized distress thermometer (DT) to measure distress in cancer patients. We propose using this tool to assess distress in PJI patients. MethodsIn this pilot study, a retrospective review of patients treated in our combined clinic over 2 years was conducted. In addition to providing information surrounding their treatment, patients completed a questionnaire and DT, adapted with permission from the National Comprehensive Cancer Network. DT scores were compared to a chronologically collected matched aseptic control group. ResultsThere were 122 patients in the septic group and 40 patients in the aseptic group. On a scale of 0-10 (10, the highest level of distress), the septic group reported a mean DT score of 6.18 (±3.2), which was significantly higher than the aseptic mean score of 3.33 (±2.06) [P < .0001]. Over 75% of patients in the septic group reported a DT score ≥4, the cutoff used in most cancer centers to warrant additional support. Twenty-one percent of the septic group (26/122) reported extreme distress (defined as a score ≥10) compared to 0/40 of aseptic patients. ConclusionsPatients treated for PJI experience significantly higher levels of distress compared to aseptic revision patients. More attention is needed to measure and clinically address distress. Improved screening for distress would allow us to provide more comprehensive care and possibly improve compliance, outcomes, and resources available for the treatment of PJI patients.

Risk factors for prosthetic joint infections after hemiarthroplasty of the hip following a femoral neck fracture

PurposeThe primary aim of this study was to identify risk factors and validate earlier reported risk factors for Prosthetic Joint Infection (PJI) after hemiarthroplasty. The secondary aim was to assess peri‑operative clinical outcomes, adverse events and mortality rates in PJI patients after hemiarthroplasty. MethodsA prospective hip fracture database was used to obtain data for this observational cohort study. Patients who underwent hemiarthroplasty between 2011 and 2021 were included. A PJI was diagnosed by the Musculoskeletal Infection Society criteria. Univariable and multivariable analyses were performed to identify factors highly associated with a PJI. ResultsIn total, 2044 patients were analysed of which 72 patients (3.5 %) developed PJI. The multivariable analysis showed that Body Mass Index (BMI) >30 (OR2.84, P = 0.020), operating time of <45 min (OR=2.80, P = 0.002), occurrence of haematoma (OR=6.24, P<0.001), decreasing level of hemoglobin (OR=1.62, P = 0.001) and re-operation for luxation (OR=9.25, P<0.001) were significant independent prognostic risk factors for development of PJI after hemiarthroplasty. Diabetes Mellitus (OR=0.34, P = 0.018) and >20 hemiarthroplasties performed by the surgeon in the previous year (OR=0.33, P = 0.019) were prognostic protective factors. In patients with PJI, 40 % (n = 29) died within one year after surgery, compared with 27 % (n = 538) in patients without PJI (OR=1.80, P = 0.017). ConclusionIndependent significant prognostic factors highly associated with PJI after hemiarthroplasty were BMI >30, operating time of <45, decreasing level of hemoglobin, occurrence of haematoma and re-operation for luxation. Diabetes Mellitus and >20 hemiarthroplasties performed by the surgeon in the previous year were prognostic protective factors for the development of PJI. PJI was associated with significantly higher 1-year all-cause mortality.

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty

Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6±22.9 months vs. 49.6±48.4 vs. 25.0±26.6, P=.010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P=.330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2±3.7 vs. 3.7±3.9, P=.027). There was no significant difference in patient-reported outcomes across groups. Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure.

Efficacy and safety of locally applied vancomycin powder injection for the prevention of prosthetic joint infection

Purpose: To determine the efficacy and safety of locally-applied vancomycin powder injection as precaution against prosthetic joint infection (PJI).&#x0D; Methods: A total of ninety subjects on admission in Department of Limb and Joint Surgery, PLA Medical Center, who underwent surgery for arthroplasty of knee and hip, were selected for this study. They were divided into two groups comprising control group (n = 45) given routine preventive antibiotic therapy as well as treatment group (n = 45) which received routine prophylactic antibiotics in combination with vancomycin therapy. PJI and the incidence of adverse reactions within 3 months after surgery were recorded. Body temperature of the patients was recorded with a thermometer. The number of neutrophils was measured by flow cytometry, while the expression levels of IL-6 and hs-CRP in peripheral blood were determined using enzyme-linked immunosorbent assay (ELISA) preoperatively and at 24, 72 and 168 h post- therapy.&#x0D; Results: At 90 days post-therapy, there was obviously significant reduction in the degree of PJI in the vancomycin-treated subjects compared with control group (p &gt; 0.05). Moreover, within 3 days, normothermia, lowered neutrophil population and downregulated expressions of Il-6 and hs-CRP were seen in the vancomycin group, when compared to control subjects (p &lt; 0.05). However, there was no significant difference in the incidence of adverse reactions between the treatment and control groups after therapy (p &gt; 0.05).&#x0D; Conclusion: Topical application of vancomycin powder injection is safe, and regulates the body temperature of PJI patients in the short-term after surgery. Moreover, it decreases the levels of inflammatory indices. However, further clinical trials should be carried out prior to application in clinical practice.

Debridement, antimicrobials, and implant retention in the treatment of late acute and early acute Staphylococcus aureus prosthetic joint infections

Background Staphylococcus aureus is the most common microbe in prosthetic joint infections (PJIs). Debridement, antimicrobials, and implant retention (DAIR) are often-recommended treatment modality for acute PJIs, even though it has had relatively poor outcomes in some studies. In this study, we wanted to examine treatment results with a multidisciplinary team in a specialised centre and obtain further information for treatment decisions in acute Staphylococcus aureus PJIs. Methods All consecutive haematogenous late acute and postoperative early acute hip and knee Staphylococcus aureus PJIs treated with DAIR during 2011–2016 were included in this retrospective study. DAIR within three weeks from symptom onset and the exchange of modular parts were required. Results Eighty-five acute Staphylococcus aureus PJIs were treated with DAIR in 83 patients: 28 late acute and 57 early acute PJIs. The late acute PJI patients were older and had malignancies more often than the early acute PJI patients. Bacteraemia was present in 50.6% of Staphylococcus aureus PJI patients, more often in late acute (73.1%) than in early acute (40.4%) patients (p = .006). The implant was retained in 80.0%: 89.3% of the late acute and 75.4% of the early acute PJIs. In 17 joints, DAIR failed and the joint had to be removed. Fourteen of these joints were successfully replaced. One infection-related death occurred. The one-year all-cause mortality rate was 3.6%. Suppressive antimicrobial treatment was given to 22 (26.5%) patients. Conclusions Reasonably good treatment results for acute Staphylococcus aureus PJIs are achievable by DAIR in a specialised centre with a strict treatment protocol and a multidisciplinary team. If the DAIR fails, a two-stage exchange is usually still possible, with good results.

An artificial intelligence framework for the diagnosis of prosthetic joint infection based on 99mTc-MDP dynamic bone scintigraphy.

Dynamic bone scintigraphy (DBS) is the first widely reliable and simple imaging modality in nuclear medicine that can be used to diagnose prosthetic joint infection (PJI). We aimed to apply artificial intelligence to diagnose PJI in patients after total hip or knee arthroplasty (THA or TKA) based on 99mTc-methylene diphosphonate (99mTc-MDP) DBS. A total of 449 patients (255 THAs and 194 TKAs) with a final diagnosis were retrospectively enrolled and analyzed. The dataset was divided into a training and validation set and an independent test set. A customized framework composed of two data preprocessing algorithms and a diagnosis model (dynamic bone scintigraphy effective neural network, DBS-eNet) was compared with mainstream modified classification models and experienced nuclear medicine specialists on corresponding datasets. In the fivefold cross-validation test, diagnostic accuracies of 86.48% for prosthetic knee infection (PKI) and 86.33% for prosthetic hip infection (PHI) were obtained using the proposed framework. On the independent test set, the diagnostic accuracies and AUC values were 87.74% and 0.957 for PKI and 86.36% and 0.906 for PHI, respectively. The customized framework demonstrated better overall diagnostic performance compared to other classification models and showed superiority in diagnosing PKI and consistency in diagnosing PHI compared to specialists. The customized framework can be used to effectively and accurately diagnose PJI based on 99mTc-MDP DBS. The excellent diagnostic performance of this method indicates its potential clinical practical value in the future. • The proposed framework in the current study achieved high diagnostic performance for prosthetic knee infection (PKI) and prosthetic hip infection (PHI) with AUC values of 0.957and 0.906, respectively. • The customized framework demonstrated better overall diagnostic performance compared to other classification models. • Compared to experienced nuclear medicine physicians, the customized framework showed superiority in diagnosing PKI and consistency in diagnosing PHI.

A retrospective study of risk factors, causative micro-organisms and healthcare resources consumption associated with prosthetic joint infections (PJI) using the Clinical Practice Research Datalink (CPRD) Aurum database.

Prosthetic joint infection (PJI) is a serious complication after joint replacement surgery and it is associated with risk of mortality and morbidity along with high direct costs. The Clinical Practice Research Datalink (CPRD) data were utilized to quantify PJI incidence after hip or knee replacement up to 5 years after implant and a variety of risk factors related to patient characteristics, medical and treatment history along with characteristics of the original surgery were analyzed through Cox proportional hazard. 221,826 patients (individual joints 283,789) met all the inclusion and exclusion criteria of the study; during the study follow-up period (5 years), 707 and 695 PJIs were diagnosed in hip and knee, respectively. Patients undergoing joint replacement surgery during an unscheduled hospitalization had greater risk of PJI than patients whose surgery was elective; similarly, the risk of developing PJI after a secondary hip or knee replacement was about 4 times greater than after primary arthroplasty when adjusted for all other variables considered. A previous diagnosis of PJI, even in a different joint, increased the risk of a further PJI. Distribution of average LoS per each hospitalization caused by PJI exhibited a right skewed profile with median duration [IQR] duration of 16 days [8-32] and 13 days [7.25-32] for hip and knee, respectively. PJIs causative micro-organisms were dependent on the time between initial surgery and infection offset; early PJI were more likely to be multispecies than later (years after surgery); the identification of Gram- pathogens decreased with increasing post-surgery follow-up. This study offers a contemporary assessment of the budgetary and capacity (number and duration of hospitalizations along with the number of Accident and Emergency (A&E) visits) posed by PJIs in UK for the national healthcare system (NHS). The results to provide risk management and planning tools to health providers and policy makers in order to fully assess technologies aimed at controlling and preventing PJI. The findings add to the existing evidence-based knowledge surrounding the epidemiology and burden of PJI by quantifying patterns of PJI in patients with a relatively broad set of prevalent comorbidities.

Aspirin Thromboprophylaxis Following Primary Total Knee Arthroplasty Is Associated With a Lower Rate of Early Prosthetic Joint Infection Compared With Other Agents

BackgroundPatients undergoing total knee arthroplasty (TKA) are at increased risk of venous thromboembolism (VTE). Aspirin has been shown to be effective at reducing rates of VTE. In select patients, more potent thromboprophylaxis is indicated, which has been associated with increased rates of bleeding and wound complications. This study aimed to evaluate the effect of thromboprophylaxis choice on the rates of early prosthetic joint infection (PJI) following TKA. MethodsA review of 11,547 primary TKA patients from 2013 to 2019 at a single academic orthopaedic hospital was conducted. The primary outcome measure was PJI within 90 days of surgery as measured by Musculoskeletal Infection Society criteria. There were 59 (0.5%) patients diagnosed with early PJI. Chi-square and Welch-2 sample t-tests were used to determine statistically significant relationships between thromboprophylaxis and demographic variables. Significance was set at P < .05. Multivariate logistic regression adjusted for age, body mass index, sex, and Charlson comorbidity index was performed to identify and control for independent risk factors for early PJI. ResultsThere was a statistically significant difference in the rates of early PJI between the aspirin and non-aspirin group (0.3 versus 0.8%, P < .001). Multivariate logistic regressions revealed that patients given aspirin thromboprophylaxis had significantly lower odds of PJI (odds ratios = 0.51, 95% confidence interval = 0.29-0.89, P = .019) compared to non-aspirin patients. ConclusionThe use of aspirin thromboprophylaxis following primary TKA is independently associated with a lower rate of early PJIs. Arthroplasty surgeons should consider aspirin as the gold standard thromboprophylaxis in all patients in which it is deemed medically appropriate and should carefully weigh the morbidity of PJI in patients when non-aspirin thromboprophylaxis is considered. Level of EvidenceRetrospective, Therapeutic Level III.

Clinical and Histological Features of Prosthetic Joint Infections May Differ in Patients With Inflammatory Arthritis and Osteoarthritis.

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose: In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods: We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ2 test, Student t test, and Mann-Whitney U test where appropriate. Results: A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions: This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population.

205. IL-1 β gene (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of hip and knee arthroplasties but not with implants infection

Abstract Background Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications. Methods Three cytokines (IL-1-a, IL-1-β, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants lasting &amp;gt; 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels were measured. Results The TT genotype and T allele of the (+3954C/T, exon 5, rs1143634) IL-1β polymorphism were more frequent in APL patients compared to controls (p=0.03 and p=0.02, respectively). No genotypic associations in PJI patients were observed. S. epidermidis was their most frequently isolated microorganism (39.3%). Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (p&amp;lt; 0.0001). Plasma IL-1β and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (p&amp;lt; 0.03). Knee implant (HR 2.488, 95% CI 1.307-4.739, p=0.005), male gender (HR 2.252, 95% CI 1.121-4.525, p=0.023), carriages of the TT genotype of the (+3954C/T) IL-1β polymorphism (HR 3.704, 95% CI 1.274-10.753, p=0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266-9.709, p=0.016) were independently associated with a shorter implant survival by Cox regression. Conclusion Genotyping of IL-1β (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL. Disclosures All Authors: No reported disclosures.

986. Pseudomonas Prosthetic Joint Infections: Is there a role for monotherapy?

Abstract Background Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJI). Despite advancements in management, Pseudomonas PJI remains particularly difficult to treat due to fewer antibiotic options and robust biofilm formation. The purpose of this study was to better evaluate outcomes after Pseudomonas PJI treatment. Methods All hip or knee PJIs, at a single institution, with positive Pseudomonas culture were analyzed. 51 patients (29 hips and 22 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1-year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment or death within one year post-operatively. Monomicrobial and polymicrobial infections were evaluated separately. Results Among monomicrobial PJIs, ten (50.0%) patients were clear of infection at one year post-operatively. Patients treated with 2-stage exchange (n=11) had a 1-year clearance rate of 54.5% compared to 60.0% with DAIR (n=5) and 25.0% with resection or amputation (n=4). Two of six patients treated with fluoroquinolone monotherapy met 1-year infection clearance, despite fluoroquinolone sensitivity, compared to four of five patients meeting 1-year clearance when treated with combined intravenous and oral therapy for at least 6 weeks. Resistance to anti-pseudomonal agents was infrequent (20%, n=4/20), and three of ten mono- and polymicrobial PJI patients with recurrent Pseudomonas PJI developed resistance to anti-pseudomonal therapy. Polymicrobial infections were the most common presentation (54.9%) of Pseudomonas positive PJI with a mortality rate of 46.4% (n=13/28) at a median follow-up of 4.2 years [IQR: 3.4-5.7]. Conclusion Despite surgical and antibiotic treatment regimens consistent with traditional treatment algorithms, our data portrays poor clearance rate of Pseudomonas PJI with relatively poor outcomes in patients treated with oral or intravenous monotherapy. Pseudomonas infections are difficult to eradicate and likely require deviations from classical therapeutic protocols to improve treatment success. Disclosures William A. Jiranek, MD, Biomech Holdings LLC: Stocks/Bonds|DePuy, A Johnson &amp; Johnson Company: IP royalties Thorsten M. Seyler, MD, PhD, Heraeus: Paid consultant|Pattern Health: IP royalties|Restor3d: IP royalties|Smith &amp; Nephew: Paid consultant|Total Joint Orthopedics: Paid consultant|Zimmer: research.

IL-1 β gene (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of arthroplasties

Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications. Three cytokines (IL-1-a, IL-1-β, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants that were implanted for > 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels also were measured. The TT genotype and T allele of (+3954 C/T, exon 5, rs1143634) IL-1β polymorphism were more frequent in APL patients compared to controls (P = 0.03 and P = 0.02, respectively). No genotypic associations in PJI patients were observed. Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (P < 0.0001). Plasma IL-1β and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (P < 0.03). Knee implant (HR 2.488, 95% CI 1.307–4.739, P = 0.005), male gender (HR 2.252, 95% CI 1.121–4.525, P = 0.023), carriages of the TT genotype of the (+3954 C/T) IL-1β polymorphism (HR 3.704, 95% CI 1.274–10.753, P = 0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266–9.709, P = 0.016) were independently associated with a shorter implant survival by Cox regression. No genotypic associations in PJI patients were observed. Genotyping of IL-1β (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL.

Intraosseous Regional Administration of Antibiotic Prophylaxis for Total Knee Arthroplasty: A Systematic Review

BackgroundIntraosseous regional administration (IORA) of antibiotics after tourniquet inflation has recently been introduced as a technique to deliver antibiotics directly to the surgical site among patients undergoing total knee arthroplasty (TKA). MethodsPubMed and Embase were queried for studies reporting on IORA for perioperative prophylaxis during TKA. Primary outcome measures were local tissue antibiotic concentrations and rates of prosthetic joint infection (PJI). Eight studies were included for analysis. Four studies (all randomized controlled trials) compared local tissue concentrations between patients receiving IORA and intravenous (IV) antibiotics. Six studies assessed the rate of PJI among patients receiving IORA versus IV antibiotics. ResultsAll studies found a statistically significant increase in antibiotic concentration in femoral bone and fat samples in patients who were treated with IORA (44.04 μg/g [fat] and 49.3 μg/g [bone] following 500 mg of intraosseous vancomycin) versus IV (3.5 μg/g [fat] and 5.2 μg/g [bone] following 1 g IV of vancomycin). The two studies powered to determine differences in PJI rates found a statistically significant decrease in the rate of PJI among patients receiving IORA versus IV antibiotics. The incidence of PJI in patients treated with IORA and IV antibiotics across all studies was 0.3 and 1.1%, respectively. ConclusionPerioperative IORA of antibiotics in TKA provides local tissue concentrations of antibiotics that are on average 10 times higher than IV administration alone. Although more adequately powered investigations are necessary to determine the effectiveness of IORA in reducing PJI rates, adoption of IORA should be considered in high-risk patients where elevated tissue antibiotic concentrations would be of a maximum benefit.

A preliminary study on the application of deep learning methods based on convolutional network to the pathological diagnosis of PJI

ObjectiveThis study aimed to establish a deep learning method based on convolutional networks for the preliminary study of the pathological diagnosis of prosthetic joint infections (PJI).MethodsWe enrolled 20 revision patients after joint replacement from the Department of Orthopedics, the First Medical Center, General Hospital of the People's Liberation Army, from January 2021 to January 2022 (10 of whom were confirmed to be infected against 2018 ICM criteria, and the remaining 10 were verified to be non-infected), and classified high-power field images according to 2018 ICM criteria. Then, we inputted 576 positive images and 576 negative images into a neural network by employing a resNET model, used to select 461 positive images and 461 negative images as training sets, 57 positive images and 31 negative images as internal verification sets, 115 positive images and 115 negative images as external test sets.ResultsThe resNET model classification was used to analyze the pathological sections of PJI patients under high magnification fields. The results of internal validation set showed a positive accuracy of 96.49%, a negative accuracy of 87.09%, an average accuracy of 93.22%, an average recall rate 96.49%, and an F1 of 0.9482. The accuracy of external test results was 97.39% positive, 93.04% negative, the average accuracy of external test set was 93.33%, the average recall rate was 97.39%, with an F1 of 0.9482. The AUC area of the intelligent image-reading diagnosis system was 0.8136.ConclusionsThis study used the convolutional neural network deep learning to identify high-magnification images from pathological sections of soft tissues around joints, against the diagnostic criteria for acute infection, and a high precision and a high recall rate were accomplished. The results of this technique confirmed that better results could be achieved by comparing the new method with the standard strategies in terms of diagnostic accuracy. Continuous upgrading of extended training sets is needed to improve the diagnostic accuracy of the convolutional network deep learning before it is applied to clinical practice.