Suh, Gina A.

Abstract Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.

Abstract Managing pelvic osteomyelitis (POM) in the setting of stage IV pressure injuries requires multidisciplinary evaluation as well as patient and caregiver engagement and is complicated by the lack of high-evidence data to guide best practices. In this review, we describe our approach to pressure injury and POM evaluation and management through multidisciplinary collaboration and highlight areas of future research that are necessary to enhance patient outcomes, reduce healthcare costs, and improve the quality of life of those affected by POM.

Abstract We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.

Abstract Background The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79–2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11–1.15; P = .09), which also had the highest risk of treatment failure. Conclusions The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Abstract Background Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain, and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. Methods We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012 to 2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. Results Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (P < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (P = .244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (odds ratio [OR] = 2.12; 95% confidence interval [CI] = 1.24–3.64; P = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. Conclusions In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Abstract Background Native joint septic arthritis (NJSA) is diagnosed by synovial fluid analysis to evaluate for evidence of infection but may be definitively established by a positive gram stain or culture. Antibiotics given prior to synovial fluid sampling have been described to alter cell count, gram stain, and culture results and are conventionally deferred until after arthrocentesis to optimize diagnostic yield. However, there is limited data on the impact of preoperative antibiotic therapy on operative culture yield in the diagnosis of NJSA. Methods Following IRB approval, we reviewed medical records of adults diagnosed with NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The effect of preoperative antibiotic therapy on operative culture yield was evaluated through a paired analysis of preoperative and operative cultures results utilizing logistic regression along with generalized estimating equations (GEE) to account for correlations of multiple measurements on the same subject. Results A total of 299 patients with NJSA of 321 joints with the accompanying characteristics who underwent surgery met study criteria (Table 1). Joint distribution, microbiology, and antibiotic administration are outlined in Table 2. Among those treated with preoperative antibiotics, there was a significant decrease in yield between preoperative and operative cultures (68.0% to 57.1%, p < .0001), whereas in patients without preoperative antibiotic exposure, there was an increase in yield (60.9% to 67.4%, p = 0.244; Figure 1). Logistic regression analysis revealed that preoperative antibiotic exposure was more likely to decrease operative culture yield as compared to non-exposure (change, -10.9% vs. +6.5%; p = .006). Secondary analyses restricted to individuals who received preoperative antibiotics revealed that an increasing number of doses and earlier administration of initial antibiotic therapy were associated with lower rates of operative culture yield (Figure 2). Joint distribution, diagnostic/microbiologic, and antibiotic administration characteristics of 321 joints in 299 patients with native joint septic arthritis Composite Image 1: Figure 1, 2a/2b Figure 1: Change in Preoperative and Operative Culture Yield with Antibiotic Exposure Figure 2: Effect of Antibiotic Doses and Timing of Therapy on Predicted Probability of Operative Culture Positivity Conclusion In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in which antibiotic therapy was held prior to obtaining operative cultures. Disclosures Brandon J. Yuan, M.D., American Association of Orthopaedic Surgeons: Board Member|DePuy, A Johnson & Johnson Company: Advisor/Consultant|Mid America Orthopaedic Association: Board Member|Stryker: Advisor/Consultant Gina A. Suh, M.D., Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: IP royalties|Phagelux: Grant/Research Support Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support

Abstract Background Native joint septic arthritis (NJSA) of the wrist is a rare condition, with published literature suggesting an incidence of approximately 1.5% among patients presenting with acute painful and swollen wrist. The aim of this study was to investigate the characteristics, management, and outcomes of wrist NJSA at our institution. Methods We conducted a retrospective study of all adults diagnosed with wrist NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The diagnosis was confirmed based on clinical presentation, synovial fluid white blood cell count, and aspiration or operative cultures. Results A total of 557 patients developed NJSA during the study period, of whom 55 (9.9%) were diagnosed with wrist NJSA, median age was 63, with the associated demographics (Table 1). 12 (21.8%) had a history of antecedent trauma or procedure, 11 (20%) had synchronous joint infections, and 22 (40%) had positive blood cultures. The median synovial white blood cell count was 94,050/mm3 (IQR 51,920 – 139,941 /mm3). Crystals were detected in 5 patients (8.8%). Additional diagnostic data are available in Table 2. Open debridement was performed in 35 (61.4%) patients, and the rest underwent arthroscopy. Positive Gram stain results were detected in the preoperative synovial fluid of 12 (21.8%) cases. The most common pathogen isolated was Staphylococcus aureus in 13 (24%) of cases. The median duration of antimicrobial therapy was 31 days (IQR 26 – 45 days). There was no statistically significant difference in the incidence of complications between patients who underwent open debridement and those who underwent arthroscopy (Table 3). The most common complication of both groups was compromised range of motion of the wrist joint. Conclusion Native wrist septic arthritis comprised 9.9 % of all NJSA during the study period. Concomitant bacteremia and synchronous joint infections were common, highlighting the importance of obtaining blood cultures and comprehensive joint exam in this setting. Crystals and Gram stains were detected in 10 % and 22% of cases, respectively. These findings should not rule out NJSA. Decreased range of motion was common complication, affecting 21% of all cases. Disclosures Gina A. Suh, M.D., Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: IP royalties|Phagelux: Grant/Research Support Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support Brandon J. Yuan, M.D., American Association of Orthopaedic Surgeons: Board Member|DePuy, A Johnson & Johnson Company: Advisor/Consultant|Mid America Orthopaedic Association: Board Member|Stryker: Advisor/Consultant

Abstract Solutions for bone and joint infection (BJI) are needed where conventional treatments are inadequate. Bacteriophages (phages) are naturally occurring viruses that infect bacteria and have been harnessed for refractory bone and joint infections (BJI) in many case reports. Here we examine the safety and efficacy of English-language published cases of BJI since 2010 with phage therapy. From 33 reported cases of BJI treated with phage therapy, 29 (87%) achieved microbiological or clinical success, 2 (5.9%) relapsed with the same organisms, and 2 (5.9%) with a different organism. Of these 4 relapses, all but 1 had eventual clinical resolution with additional surgery or phage treatments. Eight out of 33 cases (24%) reported mild, transient adverse events with no serious events reported. Further work is needed to understand the true efficacy of phages and the role of phages in BJI. Opportunities lay ahead for thoughtfully designed clinical trials adapted to individualized therapies.