Tande, Aaron J.

Abstract Background The objective of our study is to describe the clinical presentation, management, and outcome of a large cohort with nontuberculous mycobacteria (NTM) hand infection. Methods We reviewed the medical records of all adults (≥18 years) managed at the Mayo Clinic (Rochester, MN) for NTM hand infection between 1998 and 2018. Results Our cohort included 81 patients. The median age was 61.3 (interquartile range 51.7, 69.6) years; 39.5% were immunocompromised, and 67.9% reported a triggering exposure preceding infection. Infection was deep in 64.2% and disseminated in 3.7%. Up to 16.0% received intralesional steroids because of misdiagnosis with an inflammatory process. Immunocompromised patients had deeper infection, and fewer reports of a triggering exposure. Mycobacterium marinum, Mycobacterium avium complex, and Mycobacterium chelonae/abscessus complex were the most common species. The median antibiotic duration was 6.1 (interquartile range 4.6, 9.9) months. Deep infection and infection with species other than M marinum were associated with using a greater number of antibiotics for combination therapy and an extended duration of treatment. Immunosuppression was also associated with longer courses of antibiotic therapy. Surgery was performed in 86.5% and 32.4% required multiple procedures. Ten patients, mostly with superficial infections, were treated with antibiotics alone. The 5-year cumulative rate of treatment failure was 30.3% (95% confidence interval, 20.9–44.0). Immunosuppression and intralesional steroid use were risk factors for failure. Conclusions Treatment of NTM hand infection usually requires surgery and antibiotics, but antibiotics alone may occasionally be attempted in select cases. Immunosuppression and intralesional steroids are risk factors for treatment failure.

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.

AbstractIntroductionGram‐negative bacillary bloodstream infection (GN‐BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow‐up blood cultures (FUBCs) for GN‐BSI in this population, particularly in the setting of neutropenia, is poorly defined.MethodsWe conducted a single‐center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN‐BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs.ResultsOf 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug‐resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22–8.72) and vascular catheter source (OR 4.82; CI 1.76–13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all‐cause mortality (16.7% vs. 16.6%; p = .942) and microbiologic relapse (11.1% vs. 6.0%; p = .401) within 90‐days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy.ConclusionPositive FUBCs were infrequent in neutropenic patients with GN‐BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram‐negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN‐BSI in patients with underlying immune compromise. image

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 Current approaches to diagnosing suspected native vertebral osteomyelitis (NVO) rely on imaging and microbiological workup, including blood and CT-guided biopsy cultures. These existing diagnostic methods often result in ambiguity, necessitating additional tests to distinguish NVO from its mimics. Our study aims to validate pilot findings demonstrating that an elevated neutrophil differential (PMN) in vertebral bone biopsy/ disc space fluid aspirate is associated with NVO. This may allow stratification of patients with suspected NVO into those who can be monitored closely versus those who may benefit from further invasive testing or empiric antibiotic therapy (Fig 1). Figure 1: Proposed workup of patients with suspected native vertebral osteomyelitis guided by disc space/ vertebral body neutrophil (PMN) differential. Methods This analysis examines a subset of patients from a prospective cohort study, enrolling adults referred to Mayo Clinic's neuroradiology department for spine biopsy. After collecting routine clinical specimens, the needle is rinsed with saline into an EDTA tube for automated cell count and differential analysis. To evaluate the predictive capacity of neutrophil (PMN) differential for NVO, logistic regression models were employed, and receiver operating characteristic (ROC) curve analyses were conducted for various PMN percentage cutoff points. Results In this preliminary analysis, 39 patients were included, comprising 7 patients with NVO and 32 patients with alternative diagnoses. Baseline characteristics are presented in Table 1. All NVO patients received antibiotics within two weeks of the spine biopsy. The median biopsy sample PMN percentage for NVO patients was 83.0 (77.5-88.0), compared to 65.0 (56.5-69.5) for those without NVO (p=0.005) (Fig 2A). The estimated relationship between the probability of NVO and each measure across the full range of percentages is illustrated in Fig 2B. The optimal ROC curve point corresponds to a PMN differential of 72.5% (sensitivity=0.86, specificity=0.81) (Fig 3).Table 1:Baseline Characteristics of Patients Included in the Preliminary AnalysisFigure 2:A) Distribution of spine biopsy neutrophil percent by native vertebral osteomyelitis (NVO) status, B) Loess nonparametric smoother showing the relationship between the probability of NVO and biopsy sample neutrophil percentage.Figure 3:ROC curve analysis of neutrophil percent and NVO Conclusion This preliminary analysis indicates that an elevated PMN differential in spine biopsy samples may serve as a valuable diagnostic tool for NVO, with results seemingly unaffected by recent antibiotic intake. The PMN differential cutoff of 72.5% exhibited notable sensitivity and specificity. Investigations are ongoing to further validate these findings Disclosures Brett Freedman, MD, Clear Choice Therapeutics: Stocks/Bonds|Medtronic: Grant/Research Support|Neuroinnovations: Stocks/Bonds 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

AimDebridement, antibiotics, and implant retention (DAIR) is a viable treatment option for acute periprosthetic joint infections (PJI). The landmark DATIPO trial of Bernard et al. concluded that six weeks is not non-inferior to 12-week antibiotic therapy for DAIR. However, it is unknown if suppressive antibiotic treatment (SAT) would improve patient outcomes. Therefore, our study aims to evaluate the utility of SAT after 12 weeks of therapy.MethodWe performed a retrospective study of patients with acute hip or knee PJI managed with DAIR at five institutions; in the U.S. (n=1), Netherlands (n=3), and Spain (n=1) from 2005–2020. We analyzed the effect of SAT using a Cox model among patients after 12 weeks of antibiotic treatment. The primary covariate of interest was whether the patient was on antibiotics after week 12, which was coded as a time-varying covariate. We decided a-priori to control for the clinically important risk factors such as age, sex, type of infection, modular exchange, joint, and presence of bacteremia and Staphylococcus aureus. We excluded patients who died, had treatment failure, or were lost to follow-up before 12 weeks. We defined treatment failure as infection recurrence (same or different organism), unexpected reoperation, or death due to infection.ResultsThere were 504 patients included in the study. The majority were female (58%, n=292), with a mean age of 70 years ago (SD 11). Hips and knees were equally proportioned. Primary arthroplasties represented 69% of the total cohort (n=349). Treatment failure was 11.9% in the total cohort (n=60). There was no statistically significant association between SAT after 12 weeks and treatment failure (HR 1.25, p=0.45, 95% CI 0.70–2.24). This finding was consistent across different subgroups, including hip or knee joints, early or late acute infections, cohort, and a subgroup of knee joints after 180 days.ConclusionsSAT after 12 weeks of antibiotic treatment for acute PJI managed with DAIR does not appear to improve patient outcomes.

Abstract Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P < .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

Abstract Purpose Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e‐Learning. The authors hypothesised that an e‐Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. Methods The authors conducted a randomised trial comparing two versions of a 30‐minute multimedia e‐Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human‐like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. Results There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post‐module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI −0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e‐Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats ( p > 0.05). Conclusion Application of P/E principles to an e‐Learning module led to greater perceived P/E and motivational features but did not influence knowledge.

Abstract Over the last several decades, periprosthetic joint infection (PJI) has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of PJI, focusing on frequent clinical challenges and collaborative interdisciplinary care. The more detailed review including diagnosis, surgical considerations, and a detailed antimicrobial discussion is presented in the online version.